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Consensus Interferon Study for Peginterferon Nonresponders: 41 study sites
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Enrollment Open for Phase III Trial of Daily Consensus Interferon (Infergen) Plus Ribavirin for HCV Treatment Nonresponders
SEE MORE ABOUT STUDY INCLUDING STUDY SITES & STUDY DESIGN AT END OF THIS INTERMUNE PRESS RELEASE
InterMune Inc. has initiated the DIRECT Trial, a Phase III clinical trial designed to evaluate the safety and efficacy of daily Infergen (consensus interferon) in combination with ribavirin for the treatment of patients chronically infected with hepatitis C virus (HCV) who have failed to respond to a previous course of therapy with pegylated interferon alfa (Pegasys or PEG-Intron) plus ribavirin. These patients are referred to as HCV nonresponders.
INFORMATION ABOUT HEPATITIS C
Nearly 4 million Americans are estimated to be infected with the hepatitis C virus (HCV). That is more than 3 times those with HIV/AIDS, more than 5 times those with Parkinson's disease, and more than 10 times those with multiple sclerosis.
Many people with HCV do not know that they have the virus. This is unfortunate, because HCV can seriously and silently damage the liver. Often, there are no symptoms until the late stages of the disease.
These days, many people are diagnosed after a routine blood test reveals that their liver enzymes are elevated, and further tests show that the virus is in their blood. If you know you have HCV, you can get the treatment you need that may help you overcome the virus and reduce the damage to your liver.
Hepatitis C is not an easy disease to treat. A single course of interferon, or interferon plus ribavirin, may not work in getting rid of the virus. Sometimes, another course of a different interferon may be necessary to help eliminate the virus and reduce the damage to your liver.
STUDY DESIGN
Study Design Chart
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PegIFN alfa-2a or 2b + RBV
If after 12 weeks <2 log drop in HCV RNA*
If after 24 weeks still HCV RNA+
*patients with <2 log drop in HCV RNA between week 12 & 24
Randomized to
--15 ug QD Interferon alfacon-1 + RBV(n=170)
or
--9 ug QD Interferon alfacon-1 + RBV (N=170)
or
--no treatment control arm (n=170); after week 24 may be eligible for roll-over study
PRIMARY OBJECTIVE
* Evaluate the SVR rate of a therapy of daily interferon alfacon-1 (CIFN) at either 15 µg or 9 µg plus RBV compared to no treatment in HCV-infected patients who are nonresponders to previous PegIFN-alfa plus RBV therapy
SECONDARY OBJECTIVES
* Evaluate the safety and tolerability of combination therapy of daily interferon alfacon-1 at either 15 µg or 9 µg plus RBV compared to no treatment in HCV-infected patients who are nonresponders to previous PegIFN-alfa plus RBV therapy
* Evaluate the proportion of patients with abnormal baseline serum alanine aminotransferase (ALT) levels that are normal at:
--Week 24
--Week 48
--Weeks 48 and 72
EFFICACY AND SAFETY ENDPOINTS:
-PRIMARY EFFICACY ENDPOINT
* Proportion of patients with SVR rate defined as the absence of detectable HCV RNA in serum by bDNA/TMA assay at weeks 68 and 72
-SAFETY ENDPOINTS
* Proportion of patients with
--Adverse events
--Abnormal laboratory safety tests
--BDI-II score >= 29
--Dose reductions, interruptions, and discontinuations
* Proportion of patients randomized to the treatment arms who develop anti-interferon alfacon-1 (anti-CIFN) and neutralizing antibodies
PRESS RELEASE FROM INTERMUNE CONTINUED
"HCV nonresponders represent a growing unmet medical need because retreatment options are limited and generally provide very poor response rates," said Robert L. Carithers Jr., M.D., University of Washington Medical Center and Lead Principal Investigator of the study. "Pilot studies of daily Infergen plus ribavirin in the U.S. and in Europe have shown promising response rates in the treatment of nonresponders. We hope to confirm these preliminary findings in this large, well-controlled Phase III study."
The DIRECT Trial is a randomized, open-label pivotal phase III trial enrolling 510 HCV nonresponders at approximately 40 centers in the United States. There will be three arms to the study.
Patients in the first two arms will receive combination therapy of daily Infergen at one of two dose levels (9 or 15 micrograms) plus 1000-1200 milligrams ribavirin (based on body weight) daily for up to 48 weeks.
The third arm will be a no-treatment control arm and will serve as the comparison for response rates for patients in each of the two treatment arms. Patients in the control arm who have less than a 2 log decrease in HCV RNA at 24 weeks may be eligible to rollover to an additional treatment protocol at the same two dosing levels.
The primary endpoint of the DIRECT Trial is the proportion of patients with sustained viral response (SVR), which is defined as the absence of detectable HCV RNA in serum 68 and 72 weeks after the initiation of treatment.
The secondary endpoints of the study are: the proportion of patients with quantitative measurement of serum HCV RNA levels below the level of detection at weeks 24 and 48; and the proportion of patients with abnormal serum alanine transaminase (ALT) levels at baseline, a marker of liver function, that have normal ALT levels at various time points during the study.
"The launch of this trial comes on the heels of promising data presented at the Digestive Disease Week 2004 conference (May 15 - 20, 2004, New Orleans, LA) from two investigator-sponsored studies of daily Infergen plus ribavirin combination therapy in nonresponders," said Dan Welch, Chief Executive Officer and President of InterMune.
"The results of those studies provide strong scientific rationale for a Phase III study of daily Infergen plus ribavirin. In addition to this Phase III trial, we are simultaneously conducting a Phase II study to assess the use of daily Infergen in combination with our other marketed interferon, Actimmune(R) (Interferon gamma-1b), in the treatment of HCV nonresponders."
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. Standard treatment for patients chronically infected with hepatitis C virus is pegylated interferon alfa-2 plus ribavirin. Approximately half of all patients treated do not respond. There are approximately 150,000 nonresponders in the United States and the number is growing by an estimated 50,000 each year.
About Infergen
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 conducting the INSPIRE Trial, a Phase III study of interferon gamma-1b in idiopathic pulmonary fibrosis, the GRACES Trial, a Phase III study of interferon gamma-1b in ovarian cancer and a Phase II trial in HCV nonresponders of interferon alfacon-1 plus interferon gamma-1b. 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, visit http://www.intermune.com.
STUDY RATIONALE
BACKGROUND
* Fewer than 15% of patients respond to retreatment with pegylated interferons (PegIFNs)1
* Preliminary studies suggest that daily dosing of interferon alfacon-1 (CIFN) plus ribavirin (RBV) can achieve improved outcomes2
PURPOSE
* The DIRECT (IRHC-001) trial is designed to study the efficacy and safety of daily interferon alfacon-1 plus RBV in nonresponder patients
TRIAL SUMMARY
* DIRECT is a Phase III, randomized (1:1:1), open-label research study to determine the sustained virological response (SVR) rate of combination therapy of daily interferon alfacon-1 at either
15 µg or 9 µg plus RBV (1000 mg/ patient weight
< 75 kg; 1200 mg/patient weight >= 75 kg) compared to no treatment in HCV-infected patients who are nonresponders to previous PegIFN-alfa plus RBV therapy
SAMPLE SIZE
* 510 patients
* Approximately 41 sites in the United States
* Patients randomized (1:1:1) to receive:
--15 µg interferon alfacon-I plus RBV daily for 48 weeks
or
--9 µg interferon alfacon-1 plus RBV daily for 48 weeks
or
--No treatment for 24 weeks (may be eligible to be randomized to a roll-over study, 15 µg daily interferon alfacon-1 or 9 µg daily interferon alfacon-1 plus RBV for 48 weeks)
REFERENCES
1. NIH Consensus Conference, 2002.
2. Kaiser S, et al. High dose induction therapy with consensus interferon and ribavirin for treatment naïve patients with hepatitis C. Hepatology. 2002A;36(4 pt. 2):362.A.
InterMune Hepatology
STUDY SITES
InterMune has selected trial sites in North America and the Caribbean for participation in the DIRECT Trial. Please call InterMune Medical Information at 1-888-ITMN-411 (1-888-486-6411) or email medinfo@intermune.com if you cannot find a trial site near you. Not all trial sites are listed below.
Trial sites have been activated in the following locations:
California
Cedars-Sinai Medical Center
Los Angeles, CA
Investigator: Tram Tran, MD
Contact Number: (310) 423-2641
Stanford University Medical Center
Palo Alto, CA
Investigator: Gabriel Garcia, MD
Site Contact: Dana Supan, RN
Contact Number: (650) 724-3051
UCLA
Los Angeles, CA
Investigator: Steven Han, MD
Site Contact: Val Peacock, RN
Contact Number: (310) 794-6067
UCSD Medical Center
San Diego, CA
Investigator: Tarek Hassanein, MD
Site Contact: Fatma Barakat
Contact Number: (619) 543-5459
UCSF
San Francisco, CA
Investigator: Norah Terrault, MD, MPH
Site Contact: Wendy May Real
Contact Number: (415) 514-2861
Colorado
Arapahoe Gastroenterology
Littleton, CO
Investigator: Andrzej Triebling, MD, PhD
Site Contact: Guy Kennedy, PAC
Contact Number: (303) 722-8987
Website: www.arapahoegi.com
Florida
University of Florida, Shands Hospital/MSB, Hepatology Office/MSB
Gainesville, FL
Investigator: Giuseppe Morelli, MD
Site Contact: Angie Martin
Illinois
University of Illinois at Chicago, Section of Hepatology
Chicago, IL
Investigator: Scott Cotler, MD
Site Contact: Lani Krauz, BSN, RN
Contact Number: (312) 355-3782
Indiana
Indiana University School of Medicine
Indianapolis, IN
Investigator: Paul Kwo, MD
Site Contact: Rhonda Hughes, RN
Contact Number: (317) 278-3628
Louisiana
Tulane University Health Sciences Center
New Orleans, LA
Investigator: Shobha Joshi, MD
Site Contact: Delainna Bartholomen
Contact Number: (504) 585-6902
Website: www2.tulane.edu/hsc
Missouri
Saint Louis University,
GI/Hepatology Clinical Research Unit
St. Louis, MO
Investigator: Bruce Bacon, MD
Site Contact: Cherryl Korte, RN, BSN
Website: internalmed.slu.edu/gi
New Jersey
Atlantic Gastroenterology
Egg Harbor Township, NJ
Investigator: John Santoro, DO, DACG, FACOI
Site Contact: Theresa Stevens, APN-C
Contact Number: (609) 407-1220 ext. 1108
Fax: (609) 407-1340
Website: www.atlanticgastro.com
Gastroenterology Group of South Jersey
Vineland, NJ
Investigator: Gary Matusow, DO
Site Contact: Kelly Chirico, MSN, NP-C, CCRP
Contact Number: (856) 691-1400
Fax: (856) 691-3294
The New Jersey Medical School Liver Center and
Sammy Davis, Jr. National Liver Institute
Newark, NJ
Investigator: Carroll Leevy, MD
Site Contact: Andrew Moroianu, MD
Contact Number: (973) 972-7292
New Mexico
University of New Mexico Health Sciences Center
Albuquerque, NM
Investigator: Sanjeev Arora, MD
Site Contact: Claudia Scherer
Contact Number: (505) 272-4550
New York
Beth Israel Medical Center
New York, NY
Investigator: Douglas Meyer, MD
Site Contact: Ivanka Zinc, RN, MSN, CCRC
Contact Number: (212) 420-4245
Fax: (212) 844-1967
New York Medical College,
Division of Gastroenterology and
Hepatocellular Diseases
Valhalla, NY
Investigator: Edward Lebovics, MD
Site Contact: Jody Hirsh, RPA
Contact Number: (914) 594-3448
NYU Medical Center, VA New York-
Harbor Healthcare System,
GI Section (111D)
New York, NY
Investigator: Edmund J. Bini, MD, MPH, FACP, FACG
Site Contact: Stanley John, CCRC
Contact Number: (212) 686-7500 x4477
North Shore University Hospital
Manhasset, NY
Investigator: David Bernstein, MD
Site Contact: Maly Tiev, RN
Contact Number: (516) 562-4281
Weill Cornell University Medical College
New York, NY
Investigator: Gerond Lake-Bakaar, MD
Site Contact: Jamie L. Zagorski, NP
Contact Number: (212) 746-2115
Fax: (212) 746-8152
North Carolina
Carolinas Center for Liver Disease
Charlotte, NC
Investigator: Robert Reindollar, MD
Site Contact: Martha Hudson
Contact Number: (704) 378-4371 ext. 109
Ohio
The Cleveland Clinic Foundation,
Department of Gastroenterology
Cleveland, OH
Investigator: Nizar Zein, MD
Site Contact: Marcia R. Grealis, RN, BSN
Contact Number: (216) 444-6464
Consultants for Clinical Research, Inc.
Cincinnati, OH
Investigator: Mark Jonas, MD
Site Contact: Eujenia Darakchieva
Contact Number: (513) 872-4549
Oklahoma
Baptist Medical Center, Zuhdi Transplantation Institute
Oklahoma City, OK
Investigator: Ted Bader, MD
Site Contact: Jacqui Wood, RN
Contact Number: (405) 949-6615
Oregon
The Oregon Clinic
Portland, OR
Investigator: Kenneth Flora, MD
Site Contact: Timothy W. Miller, CRC
Contact Number: (503) 963-2756
Fax: (503) 254-1723
Website: www.orclinic.com
Puerto Rico
Fundacion de Investigacion de Diego
Santurce, Puerto Rico
Investigator: Maribel Rodriguez-Torres, MD
Site Contact: Elsa Gonzalez
Contact Number: (787) 722-1248
South Carolina
Medical University of South Carolina
Charleston, SC
Investigator: Adrian Reuben, MBBS, FRCP
Site Contact: Nancy Huntley, RN
Contact Number: (843) 792-5120
Tennessee
Regional Research Institute
Jackson, TN
Investigator: Mark Swaim, MD, PhD
Site Contact: Vickie Grigsby, RN, CCRP
Contact Number: (731) 661-9559
Texas
The Liver Institute at Methodist Dallas
Dallas, TX
Investigator: Reem Ghalib, MD
Site Contact: Artise Shannon
Contact Number: (214) 947-4463
Virginia
Metropolitan Research
Fairfax, VA
Investigator: Vinod Rustgi, MD
Site Contact: Phuong Lee
Contact Number: (703) 698-9254 ext. 20
Website: www.metrohepgi.com
University of Virginia Dig. Health Center of Excellence
Charlottesville, VA
Investigator: Carl Berg, MD
Contact Number: (434) 924-2626
VCU Health System at MCV Hospital
Richmond, VA
Investigator: Mitchell Shiffman, MD
Washington
University of Washington
Seattle, WA
Investigator: Anne Larson, MD
Site Contact: Judy Kaiser, RN
Contact Number: (206) 598-3568
InterMune Hepatology
http://www.directtrial.com
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