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Consensus Interferon Study for Peginterferon Nonresponders: 41 study sites

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    NATAP - www.natap.org Consensus Interferon Study for Peginterferon Nonresponders: 41 study sites Enrollment Open for Phase III Trial of Daily Consensus
    Message 1 of 1 , Sep 14, 2004
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      NATAP - www.natap.org

      Consensus Interferon Study for Peginterferon Nonresponders: 41 study sites

      Enrollment Open for Phase III Trial of Daily Consensus Interferon (Infergen) Plus Ribavirin for HCV Treatment Nonresponders


      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.


      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 Chart

      1. Patients start with 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

      2. Then patients get Randomized to:
      --15 ug QD Interferon alfacon-1 + RBV(n=170)
      --9 ug QD Interferon alfacon-1 + RBV (N=170)
      --no treatment control arm (n=170); after week 24 may be eligible for roll-over study


      * Evaluate the SVR rate of a therapy of daily interferon alfacon-1 (CIFN) at either 15 ��g or 9 ��g plus RBV compared to no treatment in HCV-infected patients who are nonresponders to previous PegIFN-alfa plus RBV therapy


      * Evaluate the safety and tolerability of combination therapy of daily interferon alfacon-1 at either 15 ��g or 9 ��g 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



      * 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


      * 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


      "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.



      * 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


      * The DIRECT (IRHC-001) trial is designed to study the efficacy and safety of daily interferon alfacon-1 plus RBV in nonresponder patients


      * 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 ��g or 9 ��g 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


      * 510 patients
      * Approximately 41 sites in the United States
      * Patients randomized (1:1:1) to receive:
      --15 ��g interferon alfacon-I plus RBV daily for 48 weeks
      --9 ��g interferon alfacon-1 plus RBV daily for 48 weeks
      --No treatment for 24 weeks (may be eligible to be randomized to a roll-over study, 15 ��g daily interferon alfacon-1 or 9 ��g daily interferon alfacon-1 plus RBV for 48 weeks)


      1. NIH Consensus Conference, 2002.
      2. Kaiser S, et al. High dose induction therapy with consensus interferon and ribavirin for treatment na��ve patients with hepatitis C. Hepatology. 2002A;36(4 pt. 2):362.A.

      InterMune Hepatology


      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@... 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 | Colorado | Florida | Illinois | Indiana | Louisiana | Missouri | New Jersey | New Mexico |
      New York | North Carolina | Ohio | Oklahoma | Oregon | Puerto Rico | South Carolina | Tennessee | Texas | Virginia | Washington |


      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

      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

      San Francisco, CA
      Investigator: Norah Terrault, MD, MPH
      Site Contact: Wendy May Real
      Contact Number: (415) 514-2861


      Arapahoe Gastroenterology
      Littleton, CO
      Investigator: Andrzej Triebling, MD, PhD
      Site Contact: Guy Kennedy, PAC
      Contact Number: (303) 722-8987
      Website: www.arapahoegi.com


      University of Florida, Shands Hospital/MSB, Hepatology Office/MSB
      Gainesville, FL
      Investigator: Giuseppe Morelli, MD
      Site Contact: Angie Martin


      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 University School of Medicine
      Indianapolis, IN
      Investigator: Paul Kwo, MD
      Site Contact: Rhonda Hughes, RN
      Contact Number: (317) 278-3628


      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


      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


      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


      Baptist Medical Center, Zuhdi Transplantation Institute
      Oklahoma City, OK
      Investigator: Ted Bader, MD
      Site Contact: Jacqui Wood, RN
      Contact Number: (405) 949-6615


      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


      Regional Research Institute
      Jackson, TN
      Investigator: Mark Swaim, MD, PhD
      Site Contact: Vickie Grigsby, RN, CCRP
      Contact Number: (731) 661-9559


      The Liver Institute at Methodist Dallas
      Dallas, TX
      Investigator: Reem Ghalib, MD
      Site Contact: Artise Shannon
      Contact Number: (214) 947-4463


      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


      University of Washington
      Seattle, WA
      Investigator: Anne Larson, MD
      Site Contact: Judy Kaiser, RN
      Contact Number: (206) 598-3568
      InterMune Hepatology


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