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A Study Of Maraviroc In HIV Co-Infected Subjects With Hepatitis C And/Or Hepatitis B

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01327547
First received: March 22, 2011
Last updated: December 9, 2014
Last verified: December 2014
  Purpose

To describe liver enzyme elevations in patients who are coinfected with HIV and either Hepatitis C (HCV) and/or Hepatitis B (HBV) receiving maraviroc or placebo in combination with their current suppressive anti-HIV drug therapy.


Condition Intervention Phase
HIV Coinfection
Drug: Maraviroc
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Blinded, Placebo-controlled Study To Evaluate The Safety Of Maraviroc In Combination With Other Antiretroviral Agents In Hiv-1-infected Subjects Co-infected With Hepatitis C And/or Hepatitis B Virus

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Percentage of Participants With Grade 3 and Grade 4 Alanine Aminotransferase (ALT) Abnormalities at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Percentage of participants with Grade 3 or Grade 4 ALT abnormalities defined as >5x upper limit of normal (ULN) for participants whose baseline ALT ≤ULN, or >3.5x baseline for participants whose baseline ALT >ULN, at Week 48 in the maraviroc arm versus the placebo arm. The baseline was defined as the last measurement prior to Day 1 dosing.


Secondary Outcome Measures:
  • Time to Development of Grade 3 and Grade 4 ALT Abnormalities at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Time taken in days to development of Grade 3 and Grade 4 ALT abnormalities defined as >5x ULN for subjects whose baseline ALT ≤ULN, or >3.5x baseline for subjects whose baseline ALT >ULN, at Week 48.

  • Percentage of Participants With Grade 3 and Grade 4 ALT Abnormalities Associated With a Change From Baseline ALT >100 IU/L at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Percentage of participants who had Grade 3 and Grade 4 ALT abnormalities associated with a change from baseline ALT >100 IU/L during the 48-week period. Baseline will be defined as the last measurement prior to Day 1 dosing.

  • Time to Development of Grade 3 and Grade 4 ALT Abnormalities at Week 48 Associated With a Change From Baseline ALT >100 IU/L [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Time to development of Grade 3 and Grade 4 ALT abnormalities associated with a change from baseline ALT >100 IU/L during the 48-week period. Baseline will be defined as the last measurement prior to Day 1 dosing.

  • Percentage of Participants With Hy's Law Abnormalities at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Hy's law was defined as a total bilirubin >2x ULN with a simultaneous ALT or aspartate transaminase (AST)>3x ULN, excluding participants with an alkaline phosphatase>3x ULN

  • Percentage of Participants With Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Concentration <40 Copies/mL at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    The Food and Drug Administration (FDA's) snapshot algorithm was used to derive the efficacy endpoint of the proportion of participants with HIV-1 RNA <40 copies/mL at Week 48. This algorithm included the missing data imputation method and used the plasma HIV-1 RNA concentration in the visit window only, followed the "virology-first principle" and considered a participant who had a missing plasma HIV-1 RNA concentration, or switched to a prohibited background anti-retroviral regimen or discontinues from the study or study drug as a failure (MSDF).

  • Change From Baseline in CD4+ and CD8+ Cell Counts at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Immunologic response (magnitude of change in CD4+ and CD8+ cell counts from baseline) was measured. Baseline value for CD4 and CD8 is defined as the pre-dose measurement taken at Day 1 visit.

  • Change From Baseline in Markers of Immune Activation: CD38 Expression on CD4 and CD8 Cells - Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine markers of immune activation namely CD38 expression on CD4 and CD8 cells.

  • Change From Baseline in Markers of Immune Activation: C-reactive Protein (CRP) - Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine markers of immune activation namely CRP.

  • Change From Baseline in Markers of Immune Activation: D Dimer - Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine markers of immune activation namely D-Dimer.

  • Change From Baseline in Markers of Immune Activation: Transforming Growth Factor-beta (TGF Beta) - Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine markers of immune activation namely TGF beta.

  • Change From Baseline in Plasma Hepatitis C Virus (HCV) RNA at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine HCV RNA using the Roche COBAS Ampliprep/COBAS HCV Taqman assay, RUO version (LOD=15 IU/mL).Baseline value for HCV RNA/HBV DNA is defined as the pre-dose measurement taken at Day 1 visit.

  • Change From Baseline in Plasma Hepatitis B Virus (HBV) DNA at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Plasma samples were used to determine HBV DNA using the Roche COBAS Taqman HBV assay. Baseline value for HCV RNA/HBV DNA is defined as the pre-dose measurement taken at Day 1 visit.

  • Change From Baseline in Enhanced Liver Fibrosis (ELF) Test at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on an ADVIA Centaur XP and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1).

    ELF score < 7.7: no to mild fibrosis; ≥ 7.7 — < 9.8: Moderate fibrosis; ≥ 9.8 — < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.


  • Change From Baseline in the Hepatic Elastography (FibroscanTM) at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Participants had transient hepatic elastography using FibroScan technology. It rapidly and non invasively measures hepatic tissue stiffness. Through a probe, a low frequency vibration of low amplitude is transmitted to the liver. The velocity of the wave that is generated during the procedure correlates directly with tissue stiffness as it passes through the liver; the harder or stiffer the liver, the faster the shear wave propagates. Results are reported in kilopascals (kPa). A negative change in the fibroscan values (i.e. decrease in liver stiffness) correlates with a decrease in fibrosis and thus improved outcome.


Enrollment: 120
Study Start Date: May 2011
Estimated Study Completion Date: March 2015
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.0 Drug: Maraviroc
150mg, 300mg or 600mg twice daily x 144 weeks; dosing dependent on components of the current suppressive anti-HIV therapy
Other Name: Selzentry, Celsentri
Placebo Comparator: 2 Drug: Placebo
150mg, 300mg or 600mg twice daily x 144 weeks; dosing dependent on components of the current suppressive anti-HIV therapy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV coinfected with HCV and/or HBV.
  • Undetectable HIV-1 RNA for at least 3 months prior to the screening visit
  • Treatment with current antiretroviral therapy (3-6 drugs excluding low-dose ritonavir) for at least 5 months.

Exclusion Criteria:

  • Currently receiving maraviroc.
  • Active opportunistic infections.
  • ALT and/or AST >5x upper limit of normal.
  • Direct bilirubin >1.5x upper limit of normal.
  • Severe or decompensated liver disease.
  • Liver disease unrelated to viral hepatitis infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327547

  Hide Study Locations
Locations
United States, California
The Office of Dr. Franco Antonio Felizarta, M.D.
Bakersfield, California, United States, 93301
AIDS Research Alliance
Los Angeles, California, United States, 90015
Alameda County Medical Center
Oakland, California, United States, 94602
University of California
Sacramento, California, United States, 95817
University of California Davis Research
Sacramento, California, United States, 95811
UCSF - San Fancisco General Hospital
San Francisco, California, United States, 94110
United States, Florida
Community AIDS Resource Inc dba Care Resource
Miami, Florida, United States, 33137
University of South Florida Health - HIV Clinical Research Unit
Tampa, Florida, United States, 33602
Rowan Tree Medical, P.A.
Wilton Manors, Florida, United States, 33305
United States, Georgia
Georgia Regents Medical Center
Augusta, Georgia, United States, 30912
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New Jersey
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
I.D. Consultants, P.A.
Charlotte, North Carolina, United States, 28209
United States, Oregon
Kaiser Permanente Sunnybrook Medical Office
Clackamas, Oregon, United States, 97015
Kaiser Permanente Northwest
Portland, Oregon, United States, 97227
United States, Texas
Southwest Infectious Disease Clinical Resesarch
Dallas, Texas, United States, 75001
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University Health Care Center Downtown
San Antonio, Texas, United States, 78207
Czech Republic
Fakultni nemocnice Brno
Brno, Czech Republic, 625 00
France
Hopital de la Croix Rousse
Lyon cedex 4, France, 69317
Hopital Tenon, Service des Maladies Infectieuses
Paris, France, 75020
Centre Hospitalier Cochin Saint Vincent de Paul
Paris CEDEX 14, France, 75679
Germany
EPIMED - Gesellschaft fuer epidemiologische und klinische Forschung in der Medizin mbH
Berlin, Germany, 12157
Universitaetsklinikum Bonn, Immunologische Ambulanz HIV
Bonn, Germany, 53127
ifi - Studien und Projekte GmbH
Hamburg, Germany, 20099
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin
Koeln, Germany, 50937
Ludwig-Maximilians-Universitaet, Medizinische Poliklinik - Klinikum Innenstadt
Muenchen, Germany, 80336
Hungary
Egyesített Szent István és Szent László Kórház - Rendelőintézet
Budapest, Hungary, 1097
Poland
Wojewodzki Szpital Obserwacyjno - Zakazny im. Tadeusza Browicza w Bydgoszczy
Bydgoszcz, Poland, 85-030
SPZOZ Wojewodzki Szpital Zakazny
Warszawa, Poland, 01-201
EMC Instytut Medyczny S.A. Przychodnia przy ul. Lowieckiej
Wroclaw, Poland, 50-220
Puerto Rico
Ararat Research Center
Ponce, Puerto Rico, 00717
Farmacia UPR-CTU
San Juan, Puerto Rico, 00935
University of Puerto Rico - School of Medicine
San Juan, Puerto Rico, 00935
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Reina Sofia - Hospital Provincial
Cordoba, Spain, 14004
Hospital Carlos Iii
Madrid, Spain, 28029
Hospital Nuestra Señora de Valme
Sevilla, Spain, 41014
Consorcio Hospital General Universitario de Valencia
Valencia, Spain, 46014
United Kingdom
Harrison Wing Research Office, Guys and St. Thomas' NHS Foundation Trust
London, United Kingdom, SE1 7EH
St Stephen's AIDS Trust
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
ViiV Healthcare
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01327547     History of Changes
Other Study ID Numbers: A4001098, 2010-021994-35
Study First Received: March 22, 2011
Results First Received: April 9, 2014
Last Updated: December 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
HIV coinfection
maraviroc
CCR5 blocker
entry inhibitor
liver disease
viral hepatitis

Additional relevant MeSH terms:
Hepatitis
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on February 27, 2015