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New Study of SCH '690' CCR5 Inhibitor for Treatment-experienced Patients
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"Safety and Effectiveness of the Oral HIV Entry Inhibitor SCH 417690 in HIV Infected Patients"
ACTG Study A5211: Phase 2 Trial of new CCR5 Entry Inhibitor
This study is currently recruiting patients.
Link to report at Retrovirus Conference 2004 on SCH 417690:
http://www.natap.org/2004/CROI/croi_10.htm
New treatment options are critical for treatment-experienced HIV infected patients with drug resistance. HIV entry inhibitors have been shown effective in patients with resistance to other anti-HIV drugs. This study will test the safety and effectiveness of three different doses of SCH 417690 (formerly known as Schering D or SCH-D) in HIV infected patients.
The AIDS Clinical Trials Group is conducting a Phase 2 trial of a new CCR5 entry inhibitor (SCH-417690 from Schering-Plough). This new drug has shown good antiviral activity in its small Phase 1 trial as monotherapy (presented at CROI in February, 2004) and is now being studied as part of a HAART regimen in 120 patients with CCR5-only virus who have >= 5000 copies/mL HIV RNA while receiving a ritonavir-containing 3-drug regimen (you must have been on that regimen for at least 8 weeks). At least one previous 3-drug regimen must have resulted in virologic failure. Exclusion of patients who are HCV + or have CD4 counts below 50 is being eliminated by amendment.
Screening for eligibility to enter the trial may take as long as six weeks, after which eligible patients are randomized to receive one of three doses of SCH-417690 or placebo (three chances out of four to receive active SCH-417690) while continuing the current HAART regimen for two weeks. After the initial two weeks of study, all patients continue their randomized SCH-417690 and also have their HAART regimen changed to new drugs which have been determined through viral sensitivity testing to be the best new regimen for them. This "optimized" regimen is continued for the remainder of one year or until (or if) virologic failure occurs. Patients may receive Fuzeon as part of the optimized regimen, if appropriate. The ACTG supplies the SCH-417690 (or placebo), but not the underlying HAART regimen. During the first four weeks of the study, participants are monitored for safety and HIV RNA weekly; thereafter, clinic visits are scheduled every 1-2 months for the remainder of the study.
There are a number of other criteria for eligibility for the trial that mostly are intended to assure the safety of participants and to contribute to the homogeneity of the study population. These are carefully explained to any potential study volunteer before informed consent is requested. These issues of eligibility and informed consent are particularly important in the context of a Phase 2 trial which, by definition, involves a new, unproven and unapproved drug being studied in a relatively small number of patients for the purpose of determining its safety and the activity of several dose levels. It should be clear from this description that participation in a Phase 2 trial carries a somewhat higher risk to the patient than is true of later stage Phase 3 trials or trials conducted after FDA approval of a drug. However, for patients who choose to participate, a Phase 2 trial may provide access to potentially important new drugs considerably earlier than they will be available more widely.
Study A5211 is being conducted at all NIH-funded ACTG sites in the US. These are 42 sites around the US; contact information is available at www.clinicaltrials.gov (enter trial # A5211). Individuals who may be eligible and interested in participating in AACTG study 5211 are encouraged to be referred, or to self-refer to their nearest ACTG site. Enrollment to the trial will remain open until the full 120 volunteers are enrolled.
Official Title: Phase II, Randomized, Double-Blind Study of the Safety and Efficacy of SCH 417690 (An Orally Administered HIV-1 Entry Inhibitor) in HIV-Infected, Treatment-Experienced Subjects Further Study Details:
Expected Total Enrollment: 120
SCH 417690 is an oral HIV-1 entry inhibitor that targets the CCR5 receptor of T cells. SCH 417690 has been shown safe, well-tolerated, and active in Phase I clinical trials in treatment-naive HIV infected patients. The goal of this study is to evaluate the antiretroviral activity of three dose levels of SCH 417690 in HIV infected, treatment experienced patients who are failing their current ritonavir-containing antiretroviral therapy (ART).
The study will last a maximum of 48 weeks. Patients will be randomly assigned to one of 4 groups. Group 1 will receive placebo; Group 2 will receive 5 mg SCH 417690 daily; Group 3 will receive 10 mg SCH 417690 daily; and Group 4 will receive 15 mg SCH 417690 daily. All patients will continue their current ART (not provided by the study). After two weeks, patients will receive ART optimized by the results of genotypic/phenotypic testing performed at study screening.
Physical exams and blood work will occur at study entry, Day 4, and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood will be drawn twice, at least 2 hours apart, at both Weeks 2 and 8 for SCH 417690 pharmacokinetic analysis. Patients will undergo an electrocardiogram (EKG) at Weeks 2, 8, 24, and 48. Patients will be assessed for peripheral neuropathy at study entry and Weeks 24 and 48, and will be asked to complete an adherence questionnaire at entry and Weeks 2, 8, 16, 24, 32, 40, and 48.
Eligibility
Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both
Criteria
Inclusion Criteria for Step 1:
• HIV infected
• Experiencing virologic failure on current ART regimen
• Current ART regimen contains ritonavir (100 to 800 mg/day) and has been stable for at least 8 weeks prior to study entry. If amprenavir or fosamprenavir is part of the regimen, 200 to 800 mg/day ritonavir must be used for at least 2 weeks prior to study entry.
• Experienced virologic failure on at least one ART regimen containing 3 or more drugs prior to current failing regimen
• CD4 count of 50 cells/mm3 or more within 6 weeks prior to study entry
• HIV viral load of 5000 copies/ml or more within 6 weeks prior to study entry
• HIV strain of R5-only phenotype within 6 weeks prior to study entry
• Willing to use acceptable forms of contraception
• Able and willing to adhere to study dose and visit schedule
Exclusion Criteria for Step 1:
• Hepatitis C antibody and RNA positive
• Hepatitis B surface antigen positive
• Efavirenz or nevirapine use within 8 weeks of study entry
• Vaccination within 2 weeks prior to study screening
• Investigational agents within 30 days prior to study entry
• Systemic cancer chemotherapy or other systemic cytotoxic agents within 30 days prior to study entry
• Immunosuppressants within 30 days prior to study entry. Systemic corticosteroids at replacement doses (10 mg/day prednisone or less) are not excluded.
• Immunomodulators within 30 days prior to study entry
• Considered at risk for seizure: history of seizure, recent history of head trauma with loss of consciousness, central nervous system (CNS) tumors, or other CNS problems that, in the opinion of the investigator, pose increased risk for seizure
• Medications to prevent seizures or with the potential to cause seizures within 30 days prior to study entry
• Allergy to SCH 417690 or its components
• Alcohol or drug abuse that, in the opinion of the investigator, would interfere with the study
• Serious illness requiring systemic treatment or hospitalization. A patient who is clinically stable on therapy is not excluded.
• Any clinically significant disease or condition that, in the opinion of the investigator, may interfere with the study
• Certain medications
• Pregnancy or breastfeeding
California
Stanford University, Stanford, California, 94305-5107, United States; Recruiting
Debbie Slamowitz, RN, BSN, ACRN (650) 723-2804 dslam@stanford.edu
San Mateo County AIDS Program, Stanford, California, 94305-5107, United States; Recruiting
Debbie Slamowitz, RN, BSN, ACRN (650) 723-2804 dslam@stanford.edu
Santa Clara Valley Medical Center, Stanford, California, 94305-5107, United States; Recruiting
Debbie Slamowitz, RN, BSN, ACRN (650) 723-2804 dslam@stanford.edu
Willow Clinic, Stanford, California, 94305-5107, United States; Recruiting
Debbie Slamowitz, RN, BSN, ACRN (650) 723-2804 dslam@stanford.edu
San Francisco General Hospital, San Francisco, California, 94110, United States; Recruiting
Michele Downing, RN, BSN 415-514-0550 Ext. 354 mdowning@php.ucsf.edu
District of Columbia
Georgetown University Medical Center, Washington, District of Columbia, 20007, United States; Recruiting
Scott P Watson, RN, BS 202-687-7387 spw3@georgetown.edu
Florida
University of Miami, Miami, Florida, 33136-1013, United States; Recruiting
Leslie Thompson, RN, BSN 305-243-3838 lthomps@gate.net
Georgia
Emory University, Atlanta, Georgia, 30308, United States; Recruiting
Ericka R Patrick, RN 404-616-6313 erpatri@emory.edu
Hawaii
University of Hawaii, Honolulu, Hawaii, 96816-2396, United States; Recruiting
Debra M Ogata-Arakaki, RN 808-737-2751 ogataara@hawaii.edu
Illinois
Cook County Hospital Core Center, Chicago, Illinois, 60612, United States; Recruiting
Joanne Despotes, RN, MPH, ACRN (312) 572-4545 jdespotes@corecenter.org
Rush-Presbyterian/St. Lukes (Chicago), Chicago, Illinois, 60612-3806, United States; Recruiting
Jan Fritsche, MS, RN, CS 312-942-4810 jfrits@rush.edu
Northwestern University, Chicago, Illinois, 60611-3015, United States; Recruiting
Baiba Berzins, MPH 312-695-5012 baiba@northwestern.edu
Indiana
Indiana University Hospital, Indianapolis, Indiana, 46202-5250, United States; Recruiting
Beth Zwickl, RN,CS, MSN 317-274-8456 bwzwickl@iupui.edu
Methodist Hospital of Indiana, Indianapolis, Indiana, 46202-5250, United States; Recruiting
Beth Zwickl, RN,CS, MSN 317-274-8456 bwzwickl@iupui.edu
Wishard Hospital, Indianapolis, Indiana, 46202, United States; Recruiting
Scott Hamilton, RN 317-630-6023 shamilt2@iupui.edu
Maryland
Johns Hopkins University, Baltimore, Maryland, 21287-8106, United States; Recruiting
Ilene P Wiggins, RN 410-614-2766 imp@jhmi.edu
University of Maryland, Institute of Human Virology, Baltimore, Maryland, 21201, United States; Recruiting
Sandy Zaremba, RN, CCRC 410-706-1476 zaremba@umbi.umd.edu
Massachusetts
Boston Medical Center (Harvard), Boston, Massachusetts, 02118, United States; Recruiting
Betsy Adams, RN, BSN 617-414-7082 betsy.adams@bmc.org
Harvard (Massachusetts General Hospital), Boston, Massachusetts, 02114, United States; Recruiting
Teri Flynn, RN, ANP 617-724-0072 tflynn@partners.org
Beth Israel Deaconess - West Campus, Boston, Massachusetts, 02215, United States; Recruiting
Helen Fitch, RN, BSN 617-632-0785 hfitch@caregroup.harvard.edu
Missouri
Washington University (St. Louis), St. Louis, Missouri, 63108-2138, United States; Recruiting
Michael Klebert, RN-C, MSN 314-454-0058 mklebert@im.wustl.edu
New York
Beth Israel Medical Center, New York, New York, 10003, United States; Recruiting
Ann Marshak 212-420-4432 amarshak@bethisraelny.org The Cornell Clinical Trials Unit, New York, New York, 10021, United States; Recruiting
Valery Hughes, NP 212-746-4393 vah9001@nyp.org Chelsea Clinic, New York, New York, 10011, United States; Recruiting
Todd Stroberg, RN 212-746-7198 tstrober@nyp.org
NYU/Bellevue, New York, New York, 10016-6481, United States; Recruiting
Maura Laverty, RN 212-263-6565 maura.laverty@med.nyu.edu
University of Rochester Medical Center, Rochester, New York, 14642-0001, United States; Recruiting
Carol Greisberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.edu
Community Health Network, Inc., Rochester, New York, 14642-0001, United States; Recruiting
Carol Greisberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.
Columbia University, New York, New York, 10032-3784, United States; Recruiting
Mykyelle Crawford, RN, BSN 212-305-2665 mc675@columbia.edu
Ohio
Case Western Reserve University, Cleveland, Ohio, 44106-5083, United States; Recruiting
Jane Baum, BSN, RN 216-844-2546 baum.jane@clevelandactu.org
Ohio State University, Columbus, Ohio, 43210, United States; Recruiting
Todd L Lusch, BA 614-293-8112 lusch-1@medctr.osu.edu
University of Cincinnati, Cincinnati, Ohio, 45267-0405, United States; Recruiting
Tammy Powell, RN 513-584-8373 powelltm@email.uc.edu
Pennsylvania
University of Pennsylvania, Philadelphia, Philadelphia, Pennsylvania, 19104, United States; Recruiting
Joseph Quinn, RN 215-349-8092 joseph.quinn@uphs.upenn.edu
Presbyterian Medical Center - Univ. of PA, Norristown, Pennsylvania, 19401, United States; Recruiting
Maureen T O'Connell, RN, BSN 215-349-8092 maureen.oconnell@uphs.upenn.edu
University of Pittsburgh, Pittsburgh, Pennsylvania, 15213-2582, United States; Recruiting
Christine Tripoli, BSN, RN 412-647-0771 tripolica@msx.upmc.edu
Rhode Island
The Miriam Hospital, Providence, Rhode Island, 02906, United States; Recruiting
Joan Gormley, BSN 401-793-4396 jgormley@lifespan.org
Rhode Island Hospital, Providence, Rhode Island, 02906, United States; Recruiting
Joan Gormley, BSN 401-793-4396 jgormley@lifespan.org
Stanley Street Treatment and Resource, Providence, Rhode Island, 02906, United States; Recruiting
Joan Gormley, BSN 401-793-4396 jgormley@lifespan.org
Tennessee
Comprehensive Care Clinic, Nashville, Tennessee, 37203, United States; Recruiting
Janet Nicotera, RN, BSN 615-467-0154 Ext. 108 janet.nicotera@vanderbilt.edu
Texas
University of Texas, Galveston, Galveston, Texas, 77555-0435, United States; Recruiting
Carrie Derkowski, BS 409-747-0241 caderkow@utmb.edu
Puerto Rico
University of Puerto Rico, San Juan, 00936-5067, Puerto Rico; Recruiting
Sylvia I Davila, BS, MS (787) 759-9595 sdavila@rcm.upr.edu
Study chairs or principal investigators
Roy M. Gulick, MD, MPH, Study Chair, Cornell HIV Clinical Trials Unit
Charles Flexner, MD, Study Chair, Johns Hopkins University Hospital
Daniel Kuritzkes, MD, Study Chair, Harvard Medical School, Partners AIDS Research Center
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