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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: November 13, 2014
Last verified: November 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: 138
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

  Show 44 Study Locations
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: November 13, 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:
Coinfection
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Infection
Liver Diseases
Parasitic Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014