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Study |
Regimen |
SVR: genotype 1 & high viral load |
SVR: genotype 1 & low viral load |
| Manns 2001 | Peg-Intron 1.5 µg/kg once weekly + RBV 800 mg/day for 48 weeks |
30% (78/256)
|
68% (63/92)
|
Fried 2002 |
Pegasys 180 µg once weekly + RBV 1,000–1,200 mg/day according to weight for 48 weeks |
41% (74/182) |
56% (64/115) |
| Hadziyannis 2004 | Pegasys 180 µg once weekly + RBV 800 mg/day for 48 weeks |
35% (67/190) |
53% (32/60)) |
People with genotype 1 and high viral loads face the following pressing questions about treatment:
- Is there any difference between Peg-Intron and Pegasys?
- For Peg-Intron, will the lower dose (1.0 µg/kg) be as effective as the higher dose (1.5 µg/kg)?
- What’s the best dose of ribavirin?
The question about proper dosing of Peg-Intron should be answered by IDEAL. But a closer look at the data from a study comparing lower and higher doses of Peg-Intron monotherapy may give people with high viral loads cause for concern:
End
of Treatment Response (ETR) and SVR in Genotype 1 by Viral Load and Dose
of Peg-Intron
| Dose & hepatitis C viral load |
ETR |
SVR |
| Lower dose (1.0 µg/kg) & low viral load |
43% (18/42)
|
38% (16/42)
|
| Lower dose (1.0 µg/kg) & high viral load |
20% (32/157) |
8% (12/157) |
| Higher dose (1.5 µg/kg) & low viral load |
50% (28/56) |
34% (19/56) |
| Higher dose (1.5 µg/kg) & high viral load |
35% (59/167) |
7% (12/167) |
| Lindsay 2001 | ||
The SVR rates for both Peg-Intron doses were similar. But the end-of-treatment response rates (the percentage of people with undetectable viral loads at the time of stopping therapy) are substantially better in people taking higher dose Peg-Intron (35% vs. 20%) for people with high viral loads. This raises questions about how people with high viral loads will fare in the low-dose Peg-Intron arm.
Ribavirin dosing raises other important concerns. Growing evidence suggests that maintaining an adequate dose of ribavirin increases the likelihood of achieving an SVR. But ribavirin can also cause hemolytic anemia (a drop in hemoglobin levels, reflecting the destruction of red blood cells). Hemolytic anemia can result in fatigue and other side effects. As a result, many people starting HCV treatment have to reduce their ribavirin doses, potentially lowering their chances of achieving an SVR.
To counteract this toxicity, physicians are increasing prescribing red cell growth factors (erythropoietin or EPO, marketed as Procrit and Aranesp) to reverse anemia and maintain people on adequate ribavirin doses. Many leading clinicians are even using EPO proactively, to prevent the need for ribavirin dose reduction before hemoglobin levels drop too far. Final research data supporting this strategy is not yet available, but the goal is to increase SVR rates by maintaining original ribavirin doses.
Based on data from large HCV treatment studies, Schering-Plough has estimated that between 14% and 22% of people in IDEAL will require ribavirin dose reductions due to drops in hemoglobin levels. The IDEAL study protocol dictates a reduction in ribavirin dose when hemoglobin levels fall below 10 g/dL. After dose reduction, EPO can be used to restore hemoglobin levels and allow a return to original ribavirin dosing, at the discretion of the treating physician.
The catch is that the protocol mandates different reductions in ribavirin dosage, depending on whether the study participant is in the Pegasys arm or a Peg-Intron arm. People in the Pegasys arm will have their ribavirin dose reduced to 600 mg. But people in a Peg-Intron arm will have a two-step dose reduction, first lowering the ribavirin dose 600-1,000 mg, depending on original dose, and then down another 200 mg if necessary.
This apparent double standard led some IDEAL study investigators to raise concerns that the different dose reduction protocols would bias the results of the Pegasys/Peg-Intron comparison in favor of Peg-Intron.
Schering-Plough explains that the FDA required different dose reduction protocols based on available data. The two-step dose reduction for the Peg-Intron arms has been studied in the WIN-R trial, but never researched in Pegasys studies. The Pegasys dose reduction scheme is based on the protocol used in the original trials leading to FDA approval of Pegasys.
In response to these concerns, Schering-Plough has countered that overall, people in the Pegasys arm will actually receive marginally higher average doses of ribavirin than people in the Peg-Intron arms. This projection presumably rests on the assumption that a substantial number of people receiving 1,400 mg of ribavirin with Peg-Intron will require ribavirin dose reductions.
A final question is how the different ranges of initial weight-based ribavirin doses (800-1,400 mg for Peg-Intron arms, vs. 1,000-1,200 for the Pegasys arm) will affect treatment responses. Schering-Plough estimates that about 14% of study participants will fall into the lowest weight category, receiving 800 mg of ribavirin with Peg-Intron or 1,000 mg of ribavirin with Pegasys. In theory, the 800 mg dose (with Peg-Intron) may be more tolerable and easier to maintain in this group, while the 1,000 mg dose (with Pegasys) may require more reductions to 600 mg (thus possibly compromising treatment efficacy).
Schering-Plough also estimates that about 11% of study participants will fall into the highest weight category, receiving 1,400 mg of ribavirin with Peg-Intron or 1,200 mg of ribavirin with Pegasys. In theory, the higher 1,400 mg ribavirin dose may be more effective for this sub-group.
What
Will We Learn from IDEAL?
IDEAL will tell us if there are any significant differences in SVR rates between the three treatment regimens. In particular, IDEAL should tell us whether low-dose Peg-Intron works as well as high-dose Peg-Intron when used in combination with ribavirin in people with genotype 1.
IDEAL will also look at whether there are differences in SVR rates between the three regimens based on whether people have a high or low hepatitis C viral load. In the case of viral load, unless the differences are very large, IDEAL will not be able to determine which is the best treatment regimen.
IDEAL will not be able to tell us whether Peg-Intron is better or worse than Pegasys, because different doses of ribavirin will be used. All study participants will get a ribavirin dose that is based on their weight, but IDEAL lacks the statistical power to compare SVR rates between different weight groups. About 75% of study participants will fall into the middle weight range and receive 1,000-1,200 mg of ribavirin regardless of which arm they are assigned to. That leaves 25% of study participants who will receive lower (800 mg) or higher (1,400 mg) doses of ribavirin if they are assigned to the Peg-Intron arms, which may influence SVR rates.
IDEAL results will be analyzed to see whether different ribavirin dose reduction protocols affect final SVR rates. But if there are overall differences between the Pegasys and Peg-Intron arms, we won’t know if that’s because of the type of pegylated interferon used or the ribavirin dosing scheme.
Also, the Roche pilot study could show that higher doses of Pegasys and/or ribavirin are more effective in people weighing over 187 pounds who have genotype 1 and high hepatitis C viral loads. In that case, the recommended Pegasys/Copegus doses might change, making the IDEAL results irrelevant to this group.
Conclusions
The design of IDEAL represents the results of a complex negotiation between scientific research, marketing imperatives, and regulatory demands. Schering-Plough and Roche have predictably different perspectives on the value of IDEAL:
“These two
treatment regimens have never before been directly compared in a study
of this magnitude. We are confident that the results of this large
head-to-head study between Peg-Intron and Pegasys will help doctors and
patients determine the therapy that offers them the best chance for
achieving a sustained virologic response.”
— Robert J.
Spiegel, M.D., senior vice president of medical affairs and chief
medical officer, Schering-Plough Research Institute, quoted in a 5/13/04
Schering-Plough press release
“We think what is
relevant is the data that are available today. We have great confidence
in Pegasys and the wealth of data supporting it. We would welcome a
fair comparative trial, where Pegasys would be given an equal chance.
We do not believe this is the case for Schering-Plough's study including
Pegasys. It is our understanding that the ribavirin dosing regimen and
dose reductions for side effects in the trial will favor the Peg-Intron
arms. Therefore, we do not believe this study will ever yield any
unbiased information beyond what the optimal doses of Peg-Intron and
Rebetol might be.”
—
Pamela Van Houten,
director of public affairs, Roche
Regardless of company rhetoric, people considering enrolling in IDEAL—particularly those with high viral loads—should think carefully about whether this study is right for them. By joining IDEAL, study participants are randomly assigned to one of three treatment regimens, thus sacrificing the ability to work with their doctor on choosing a regimen that best suits their individual needs. In many cases, the best regimen is unclear, highlighting the potential value of IDEAL. Some doctors would chafe at IDEAL’s restrictions on the preemptive use of EPO to head off the need for protocol-dictated ribavirin dose reductions.
That’s not to say
that the study is unethical. The design has been carefully thought out,
based on the best available data from clinical trials, with the input of
many leading clinicians, and approved by both the FDA and local
Institutional Review Boards (IRBs). IDEAL will certainly provide a
wealth of valuable data to guide future treatment decisions. But this
study may not be ‘IDEAL’ for everyone.
06/02/04
New Pegasys Trial to Enroll Hepatitis C Patients Not Helped by PEG-Intron
Hepatitis C patients who
failed to respond to the first pegylated interferon combination therapy (peginterferon
alfa-2b and ribavirin) are being recruited for a new global trial of
peginterferon alfa-2a and ribavirin, it was announced at the 38th Annual
Meeting of the European Association for the Study of the Liver.
Roche, which markets peginterferon alfa-2a as Pegasys, said the trial, which ultimately expects to enroll 1,000 patients in this study from Europe, North America and Latin America, will be known as REPEAT (REtreatment with Pegasys in pATients not responding to prior Peginterferon alfa-2b/Ribavirin combination therapy).
"Non-responders," as these hepatitis C patients are called, are those who failed to achieve a sustained virological response (increasingly regarded as a "cure") as a result of their treatment, and who continued to have virus present throughout their course of therapy.
The trial will be the first to compare repeat treatment of "non-responders" who previously were treated with peginterferon alfa-2b, which is marketed by Roche competitor Schering. Previous studies using pegylated interferon to retreat "non responders" have measured themselves against earlier therapies.
Today, the standard of care is pegylated interferon and ribavirin, and most hepatitis C patients receive one of the two pegylated interferon combination therapies.
"The two pegylated interferons are different drugs, with different properties and we know that Pegasys with Copegus (ribavirin) has yielded impressive results in hepatitis C patients," said William M. Burns, head of the pharmaceutical division at Roche. "We feel it is important for this pivotal trial to show how Pegasys with Copegus can help that sizeable group of patients who have not responded to the first pegylated interferon combination therapy."
The REPEAT study will evaluate the efficacy and safety of the combination of Pegasys and Copegus given for a longer, 72-week period, as well as examining the role of an induction regimen in this treatment- resistant population, Roche said.
"We've already seen that Pegasys in combination with Copegus is a highly effective treatment in [first-time] patients with some of the most difficult-to-treat strains of the virus,"said the European lead researcher Dr. Patrick Marcellin from Hospital Beaujon in France. "Given this performance, Pegasys may prove to give these particular patients another chance to respond and be cured."
Approximately 330 patients will be enrolled at the 33 participating centers in the United States. In order to be eligible for the trial, patients must have undergone at least 12 weeks of treatment with Peg-Intron/Rebetol therapy with no response. Patients who discontinued therapy because of adverse events alone are not eligible for this study. In addition, patients must be over 18 years of age. Nationwide enrollment is currently underway for the study.
Patients will be randomized to the following treatment arms:
Group A: Initial high induction dose of Pegasys 360 mcg/week and Copegus
1000/1200mg daily for the first 12 weeks; additional treatment period of 60
weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.
Group B: Initial high induction dose of Pegasys 360 mcg/week and Copegus
1000/1200mg daily for the first 12 weeks; additional treatment period of 36
weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.
Group C: Treatment period of 72 weeks with Pegasys 180 mcg/week and Copegus
1000/1200mg daily.
Group D: Treatment period of 48 weeks with Pegasys 180 mcg/week and Copegus
1000/1200mg daily.
All patients will have a 24-week follow-up period to evaluate whether they
have achieved a sustained virologic response. Sustained virological response
refers to a patient’s continued undetectable serum hepatitis C RNA levels 24
weeks after finishing a course of treatment.
"Although the two pegylated interferons in this study belong to the same class of medications, there are differences between the two," said Jensen. "We hope that the differences between the medications and the different dosing regimens will lead to a good alternative for patients who currently have no proven options."
Pegasys and Copegus combination therapy is marketed in the U.S. by Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J. Peg-Intron and Rebetol combination therapy is marketed by Schering-Plough Corporation, based in Kenilworth, NJ.
For more information about the REPEAT trial and to locate a study site, patients can visit the "Clinical Trials" section of the American Liver Foundation website at www.liverfoundation.org or call 1-800-GO-LIVER.
###
Rush University Medical Center includes the 729-bed Presbyterian-St. Luke’s Hospital; 79-bed Johnston R. Bowman Health Center; Rush University (Rush Medical College, College of Nursing, College of Health Sciences and the Graduate College).
Important Safety Information About Pegasys (Peginterferon alfa-2a) in Combination with Copegus
Alpha interferons, including PEGASYS (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy.
Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and decompensated hepatic disease (Child-Pugh class B and C) before or during treatment with PEGASYS. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Physicians and patients are also strongly encouraged to report any pregnancies that do occur to Roche by calling 1-800-526-6367.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials (N=451) were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).
Serious adverse events included neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial
infarction), hypersensitivity (including anaphylaxis), endocrine
disorders (including thyroid disorders and diabetes mellitus), autoimmune
disorders (including psoriasis and lupus), pulmonary disorders (dyspnea,
pneumonia, bronchiolitis obliterans, interstitial pneumonitis and
sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis),
pancreatitis, and ophthalmologic disorders (decrease or loss of vision,
retinopathy including macular edema and retinal thrombosis/hemorrhages,
optic neuritis and papilledema).
Hep C: Pegasys and Copegus in Non-responders
REPEAT Trial
(REtreatment with PEgasys in pATients not responding to Peg-Intron therapy)
The trial will evaluate different regimens of combination therapy in
patients with hepatitis C who failed to generate a sustained virological
response after treatment with Peg-Intron/Rebetol therapy.
Patients in the new study will receive Pegasys® (peginterferon alfa-2a) and
Copegus (ribavirin), already approved as a first-line treatment for patients
with hepatitis C. Approximately 330 patients will be enrolled at the 33
participating centers in the United States.
Eligibility:
In order to be eligible for the trial, patients must have undergone at least
12 weeks of treatment with Peg-Intron/Rebetol therapy with no response.
Patients who discontinued therapy because of adverse events alone are not
eligible for this study. In addition, patients must be over 18 years of age.
Sites/Contacts:
Alabama
University of South Alabama, Gastroenterology, Jorge Herrera, MD
Contact: Emilie Barnett, RN 251.660.5555
California
USC Hepatitis Research and Treatment Center
Contact: Nancy Shura 323.224.5500
Medical Association, Michael Bennett, MD
Contact: Dianne Tuohy 858.277.5678
Colorado
Mountain West Gastroenterology, Terry Box, MD
Contact: Amanda McCafafery 801.944.3165
Connecticut
University of Connecticut Health Center, Herbert Bonkovsky, MD
Contact: Michelle Kelley 860.679.8156
Florida
Borland-Groover Clinic, Kyle Etzkorn, MD
Contact: Linda Burton 904.680.0871
Bach and Godofsky, Eliot Godofsky, MD
Contact: Michele Mays 941.746.2711
Georgia
Digestive Healthcare of GA, Raymond Rubin, MD
Deb Jewett or Janice Rudolph 404.355.3200
Illinois
Northwestern University Medical Center, Steven Flamm, MD
Contact: Kim Sipich 312.469.4168
Rush University Medical Center
Contact: Mary Vance 312.563.3903
Iowa
Iowa Digestive Health Disease Center, William J. Semon, DO
Contact: Sarah Hubbard 515.288.6097
Maryland
Johns Hopkins Bayview Medical Center, Rudra Rai, MD
Contact: Pnina Schwartz 443.287.5205
Massachusetts
Brigham & Women’s Hospital, Norman Grace, MD
Contact: Amanda Fretts 617.732.8435
Massachusetts General Hospital, Raymond Chung, MD
Contact: Deb Casson 617.726.6271
Minnesota
Mayo Clinic, Russell Weisner, MD
Contact: Linda Lairson 507.284.6034
Missouri
Washington University School of Medicine
Contact: Shirly Campbell 314.747.7040
Bradley L. Freilich, MD
Contact: Janay Kissinger 816.361.5525
New Jersey
Affiliates in Gastroenterology, Lawrence Stein, MD
Contact: Donna Fanelli, MSN 973.410.1800 x19
New Mexico
University of New Mexico, Sanjeez Aurora, MD
Contact: Carrie Tolson 505.272.5381
Rhode Island
Paragon Clinical Research, Dennis Mikolich, MD
Contact: Billie Jo Welliver 401.943.8662
Texas
Radiant Research, Imtiaz Alam, MD
Contact: Kathy Bevers 512.901.4557
Please check back - more trial sites will be listed shortly
nternational Hepatitis C Study to Examine New Approaches to Treat
Patients Who Did Not Benefit From Standard Therapy
--Rush University Medical Center’s Dr. Donald Jensen Leads US Study--
Contact: John Pontarelli or Chris Martin
Phone: (312) 942-5949 or 942-7820
Email: jpontare@rush.eduor
cmartin@rsh.net
CHICAGO-A new study seeks to answer one of the most challenging and important questions in hepatitis C therapy today: What is the best option for patients in whom one of the most widely prescribed treatments has failed?
The study will evaluate different regimens of combination therapy in patients with hepatitis C who failed to generate a sustained virological response after treatment with Peg-Intron/Rebetol therapy. Patients in the new study will receive Pegasys® (peginterferon alfa-2a) and CopegusŇ (ribavirin), already approved as a first-line treatment for patients with hepatitis C.
The REPEAT Trial (REtreatment with PEgasys in PATients Not Responding to Peg-Intron Therapy) is led in the U.S. by hepatologist Dr. Donald Jensen of Rush University Medical Center. The US portion of the study will enroll approximately 330 patients at 33 centers including Rush.
Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide and is the leading cause of cirrhosis and liver cancer and the number one reason for liver transplants in the U.S.
"Although we have seen significant improvements in hepatitis C therapy over the past few years, many patients still do not respond to treatment on their first attempt," said Dr. Donald Jensen, director of Hepatology at Rush University Medical Center and lead U.S. investigator in the REPEAT trial. "We hope that this trial will provide patients a proven option with another pegylated interferon if Peg-Intron combination therapy failed to work for them."
The REPEAT Trial is an international study enrolling approximately 888 patients at 98 centers in 14
|
|
New Pegasys Study for HCV+
Untreated Patients with Genotype 1, High Weight & High Viral Load
|
||
|
"Pegasys in Combination with Copegus in Previously
Untreated Patients with Chronic Hepatitis C Genotype 1 of High Viral
Count and Body Weight > 85 kg (187 lbs)" Source: www.clinicaltrials.gov This study is currently recruiting patients. Sponsored by Hoffmann-La Roche Purpose of The Study The objective of this study is to evaluate the effects of higher doses of Pegasys and Copegus in patients infected with Hepatitis C, whose body weight is greater than 85 kg (187 lbs) and who have a high viral count. CONDITION: Chronic Hepatitis C TREATMENT DRUGS: Pegylated Interferon alfa-2a in combination with Ribavirin Phase IV Study Official Title: Evaluation of the effect of Pegasys doses of 180 ug or 270 ug in combo w/ Copegus doses of 1200 mg or 1600 mg in previously untreatedpatients w/ Chronic Hepatitis C Genotype 1 of high viral count and body wt greater than 85 kg (187 lbs) Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both Criteria Inclusion Criteria: --Age greater than or equal to 18 years --Infected with Hepatitis C virus Genotype 1 --High Viral Count (HCV RNA count greater than 800,000 IU/mL) --Body Weight greater than 85 kg (187 lbs) Exclusion Criteria: --Pregnant, breast-feeding or male partners of those who are pregnant --Infection with Hepatitis C virus Genotype 2, 3, 4, 5, 6 or undetermined --Previously treated with interferon, pegylated interferon, ribavirin, viramidine, levovirin or amantadine at any previous time or any other systemic antiviral therapy or investigational drug less than or equal to 3 months prior to first dose of study drug. Exception: Patients with a limited (less than or equal to 7 day) course of acyclovir or valacyclovir for herpes more than 1 month prior to first dose of study drug are not excluded. Study Locations and Contact Information Please reference Study ID Number: PDO-NV17318 973-235-5000 (Roche tel#)or 800-526-6367 (FOR US ONLY) California San Diego, California, 92120, United States; Recruiting (619) 563-4040 Long Beach, California, 90822, United States; Recruiting (562) 826-5933 La Jolla, California, 92037, United States; Recruiting (858) 554-8097 Downey, California, 90242, United States; Completed Connecticut Farmington, Connecticut, 06030, United States; Recruiting (860) 679-8156 (860) 679-3749 Florida Gainesville, Florida, 32610-0214, United States; Recruiting (352) 392-7956 (352) 392-5454 Jacksonville, Florida, 32207, United States; Recruiting (904) 680-0871 Wellington, Florida, 33414, United States; Not yet recruiting Bradenton, Florida, 34205, United States; Recruiting (941) 746-2711 Hawaii Honolulu, Hawaii, 96817, United States; Recruiting (808) 547-6541 Illinois Chicago, Illinois, 60612, United States; Recruiting (312) 563-3903 Indiana Indianapolis, Indiana, 46214-2985, United States; Completed Iowa Iowa City, Iowa, 52242, United States; Recruiting (319) 356-1660 Massachusetts Boston, Massachusetts, 02111, United States; Recruiting (617) 636-4532 Boston, Massachusetts, 02114, United States; Terminated Minnesota Plymouth, Minnesota, 55446, United States; Terminated Missouri St. Louis, Missouri, 63104, United States; Recruiting New Jersey Princeton, New Jersey, 08540-6233, United States; Completed New York Manhasset, New York, 11030, United States; Not yet recruiting (516) 562-4281 North Carolina Chapel Hill, North Carolina, 27599-7080, United States; Recruiting (919) 966-6732 Charlotte, North Carolina, 28203, United States; Recruiting Ohio Cincinnati, Ohio, 45267, United States; Recruiting (513) 584-5245 Pennsylvania Philadelphia, Pennsylvania, 19104, United States; Not yet recruiting Pittsburgh, Pennsylvania, 15213, United States; Recruiting (412) 647-1462 (412) 647-1170 Texas Houston, Texas, 77030, United States; Not yet recruiting Utah Salt Lake City, Utah, 84121, United States; Recruiting (801) 944-3165 Virginia Richmond, Virginia, 23249, United States; Recruiting (804) 675-5021 Charlottesville, Virginia, 22906-0013, United States; Not yet recruiting (434) 924-2626 Canada, Ontario Toronto, Ontario, M5G 1L7, Canada; Terminated Puerto Rico Santurce, 00909, Puerto Rico; Recruiting (787) 722-1248 More Information Study ID Numbers NV17318 Record last reviewed May 2004 NLM Identifier NCT00077649 ClinicalTrials.gov processed this record on 2004-06-04 |
||
| Press Release Source: Schering-Plough Corporation
Nation's
Top Medical Centers Seek Participants for Largest Study Comparing
Leading Hepatitis C Treatments KENILWORTH, N.J., May 13 /PRNewswire-FirstCall/ -- Medical centers, hospitals, clinics and other treatment sites across the country are actively enrolling Americans with the hepatitis C virus (HCV) in a nationwide study that will for the first time determine which of the two FDA-approved pegylated interferon therapy regimens offers patients the best chance to eliminate the virus. The regimens being compared are PEG-INTRON® (peginterferon alfa- 2b/Schering Corporation) versus PEGASYS (peginterferon alfa-2a/ Hoffmann-La Roche, Inc.), both used in combination with ribavirin. Hepatitis C, a potentially fatal virus that infects the liver, blood and other tissues, is the most common blood-borne infection in America, and is the leading cause of liver transplantation in the United States, according to the National Institutes of Health. Approximately 4 million Americans, or about one in every 50 adults, are now infected with HCV,(1) compared to 900,000 Americans with HIV. A total of 2,880 patients at up to 100 U.S. sites will join the IDEAL study, which stands for Individualized Dosing Efficacy vs. flat dosing to Assess optimaL pegylated interferon therapy. The study is led by co-principal investigators John G. McHutchison, M.D., FRACP, Medical Director, Liver Research, Duke University Medical Center, and Mark S. Sulkowski, M.D., assistant professor of medicine in the Division of Infectious Diseases, Johns Hopkins University School of Medicine. IDEAL study sites currently open to patient enrollment can be identified via zip code search on the study's Web site: www.idealstudy.com. Patients are encouraged to check the Web site on an ongoing basis as additional study sites will be opening enrollment in the coming weeks and will be added to the Web site at that time. Unlike some clinical studies, where patients receive either active drug or placebo, all participates in the IDEAL study will receive active treatment at no cost. "The IDEAL Study offers an excellent opportunity to collect more data on hepatitis C treatment," said Alan Brownstein, president and chief executive officer of the American Liver Foundation. "Treating HCV is a long and arduous process. To give people the best chance for success in the future, we need more information." The IDEAL study will compare the efficacy and safety of individualized weight-based dosing with PEG-INTRON and REBETOL® (ribavirin, USP) to PEGASYS, which is administered as a flat dose to all patients regardless of individual body weight, and COPEGUS (ribavirin, USP) dosed either at 1,000 mg or 1,200 mg daily, in U.S. patients chronically infected with hepatitis C, genotype 1. Genotype 1 is the most common worldwide, the most difficult to treat successfully and accounts for about 70 percent of HCV infection among Americans. PEG-INTRON is a form of interferon alfa-2b that has been chemically "pegylated" so it is retained in the body longer than standard interferon, thereby providing for once weekly administration. PEGASYS is a pegylated form of interferon alfa-2a. IDEAL is sponsored by Schering-Plough Research Institute (SPRI) and is being conducted to respond to questions raised by the hepatitis C medical and patient communities. "These two treatment regimens have never before been directly compared in a study of this magnitude," said Robert J. Spiegel, M.D., senior vice president of medical affairs and chief medical officer, Schering-Plough Research Institute. "We are confident that the results of this large head-to- head study between PEG-INTRON and PEGASYS will help doctors and patients determine the therapy that offers them the best chance for achieving a sustained virologic response." About IDEAL Combination therapy with pegylated interferon, which boosts the body's immune system, and ribavirin, an oral antiviral agent, is today's standard of care when treating chronic HCV. Approximately 50 to 60 percent of individuals who are treated with this combination therapy clear the hepatitis C virus from their bodies. PEG-INTRON and REBETOL combination therapy is the most-prescribed treatment for chronic hepatitis C worldwide, with more than 300,000 patients having received this treatment since its introduction in 2001. All participants will be treated with an active study medication for up to 48 weeks, with follow-up by a physician for an additional six months. How to Participate in IDEAL To enroll in the IDEAL study, people must be diagnosed with chronic hepatitis C, genotype 1, not have received any prior treatment for hepatitis C and be between the ages of 18 and 70. To identify a study center near you, consult the study's Web site: www.idealstudy.com. The list of institutions actively enrolling patients will be updated on the Web site as additional sites open for enrollment or as patient enrollment at specific institutions is completed. IDEAL Study Locations (by city): Akron, OH Hartford, CT Pittsburgh, PA *indicates multiple study participants in this city |
InterMune Initiates Phase II Clinical Trial of Daily Infergen Plus Actimmune for the Treatment of Hepatitis C Nonresponders
BRISBANE, Calif., May 13 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) today announced that it has initiated a Phase II clinical trial of the combination of Infergen(R) (interferon alfacon-1) and Actimmune(R) (interferon gamma-1b) for the treatment of patients chronically infected with hepatitis C virus (HCV) who have failed to respond to therapy with pegylated interferon alpha 2 plus ribavirin. These patients are referred to as HCV nonresponders. Approximately half of all patients treated with pegylated interferon alpha 2 plus ribavirin do not respond to therapy. There are approximately 150,000 HCV nonresponders in the United States and the number is growing by an estimated 50,000 each year. "There is a major unmet medical need today because there are no FDA-approved treatments for HCV nonresponders. According to recent scientific presentations, retreatment with pegylated interferon alpha 2 plus ribavirin generally delivers poor response rates of between 5 and 12 percent," said Maria Sjogren, M.D., Chief, Department of Clinical Investigation, Walter Reed Army Medical Center, and the principal investigator of the trial. "A sound scientific rationale, supportive in vitro data and promising early clinical observations provide a strong basis for advancing the clinical development of this novel combination therapy." The randomized, multicenter open-label Phase II clinical trial will enroll up to 80 patients in three sequential groups. Patients will be randomized to receive either 9 or 15 micrograms of Infergen daily in combination with 50 or 100 micrograms of Actimmune three times weekly with or without daily ribavirin, for 48 weeks. The primary objective of the study is to evaluate the safety and tolerability of the combination regimen with or without ribavirin and the potential for Actimmune to replace ribavirin as an adjunct to Infergen in treating HCV nonresponders. Secondary objectives are to determine the highest well-tolerated dosing regimen, assess virologic response at the end of treatment and sustained virologic response 24 weeks after completing therapy. Compelling Rationale for Novel Interferon Combination Regimen for HCV Nonresponders There is a strong rationale for combining Infergen and Actimmune for the treatment of hepatitis C nonresponders. Published clinical research has shown that endogenous levels of interferon gamma play an important role in the clearance of acute HCV infection from the blood. In addition, in vitro experiments undertaken at InterMune have demonstrated synergistic antiviral effects for a range of doses of Infergen and Actimmune in combination. Moreover, promising interim results from a retrospective clinical analysis of this combination for the treatment of chronic hepatitis C nonresponders were presented at the annual HepDART meeting last December by Carroll Leevy M.D., Director of Clinical Affairs, The New Jersey Medical Liver Center and Sammy Davis Jr. National Liver Center, Newark, New Jersey. Dr. Leevy will present an update on the clinical experience of this novel combination at the upcoming Digestive Disease Week Conference, May 15 - 18 in New Orleans. "Our analysis of promising early virological response rates in difficult-to-treat HCV nonresponders has provided preliminary evidence in humans of enhanced antiviral effects of Infergen plus Actimmune relative to retreatment with pegylated interferons plus ribavirin," said Dr. Leevy. "An initial retrospective analysis conducted on 32 HCV nonresponders showed that 38% of patients had undetectable levels of virus in their blood following 12 weeks of combination therapy. We hope to reproduce these promising results in this more extensive and more rigorous study." About Chronic Hepatitis C According to the Centers for Disease Control an estimated 3.9 million (1.8%) Americans have been infected with HCV, of whom 2.7 million are chronically infected. Hepatitis C causes an estimated 10,000 to 12,000 deaths annually in the United States. The prevalence of chronic hepatitis C is increasing. About Infergen(R) (interferon alfacon-1) Infergen is a bio-optimized type 1 interferon alpha indicated for treatment of adult patients with chronic HCV infections with compensated liver disease and is dosed three times a week. Infergen is the only interferon alpha with data in the label regarding use in patients following relapse or non-response to treatment with certain previous treatments. The most common side effects are flu-like symptoms (i.e., headache, fatigue, fever, myalgia, and rigors). Physicians and patients can obtain additional prescribing information regarding Infergen, including the product's safety profile, by visiting http://www.infergen.com, including the black box warning for all interferon alphas regarding neuropsychiatric, autoimmune, ischemic and infectious disorders. About Actimmune(R) (interferon gamma-1b) Interferon gamma is a naturally occurring protein that stimulates the immune system. InterMune markets Actimmune for the treatment of two life-threatening congenital diseases: chronic granulomatous disease and severe, malignant osteopetrosis. The most common side effects are flu-like symptoms, including fever, headache and chills. InterMune is also conducting the INSPIRE Trial, a Phase III study of interferon gamma-1b in idiopathic pulmonary fibrosis and the GRACES Trial, a Phase III study of interferon gamma-1b in ovarian cancer. Physicians and patients can obtain additional prescribing information regarding Actimmune, including the product's safety profile, by visiting http://www.actimmune.com. About InterMune InterMune is a biopharmaceutical company focused on developing and commercializing innovative therapies in pulmonology and hepatology. For additional information about InterMune please visit http://www.intermune.com. Except for the historical information contained herein, this press release contains certain forward-looking statements that involve risks and uncertainties, including without limitation the statements indicating that: (i) interim results from a retrospective clinical analysis of this combination were promising; (ii) analysis of promising early virological response rates in difficult-to-treat HCV nonresponders has provided preliminary evidence in humans of enhanced antiviral effects of Infergen plus Actimmune relative to retreatment with pegylated interferons plus ribavirin; (iii) InterMune can reproduce the results of the initial retrospective analysis in the Phase II study. Factors that could cause or contribute to such differences include, but are not limited to those discussed in detail under the heading "Risk Factors" and the other risks and factors discussed in InterMune's 10-Q report filed with the SEC on May 10, 2004, and other periodic reports (i.e., 10-Q and 8-K) filed with the SEC, which are incorporated herein by reference. The risks and other factors that follow, concerning the above forward-looking statements in this press release, should be considered only in connection with the fully discussed risks and other factors discussed in detail in the 10-K report and InterMune's other periodic reports filed with the SEC. The forward-looking statements above are subject to the risks and uncertainties that include, without limitation, those associated with: (a) the risks and uncertainties that the trial will demonstrate a robustly positive effect on progression-free survival that is consistent with the other endpoints of the trial; (b) regulatory risks; and/or (c) the risks and other factors discussed in detail in the 10-K report.SOURCE InterMune, Inc.
Web Site: http://www.intermune.com