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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

March 22, 2011
November 13, 2014
May 2011
April 2013   (final data collection date for primary outcome measure)
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.
Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities defined as >5x upper limit of normal (ULN) for subjects whose baseline ALT ≤ULN, or or >3.5x baseline for subjects whose baseline ALT >ULN. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
At Week 48 in the maraviroc arm versus the placebo arm.
Complete list of historical versions of study NCT01327547 on ClinicalTrials.gov Archive Site
  • 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.
  • Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Time to development of Grade 3 and Grade 4 ALT abnormalities [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Time to development of Grade 3 and Grade 4 ALT abnormalities [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Time to development of Grade 3 and Grade 4 ALT abnormalities [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities associated with a change from baseline ALT >=100 IU/L [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities associated with a change from baseline ALT >=100 IU/L [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Grade 3 and Grade 4 ALT abnormalities associated with a change from baseline ALT >=100 IU/L [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Time to development of Grade 3 and Grade 4 ALT test abnormalities 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 test abnormalities associated with a change from baseline ALT >=100 IU/L [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Time to development of Grade 3 and Grade 4 ALT test abnormalities associated with a change from baseline ALT >=100 IU/L [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Hy's law abnormalities [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Hy's law abnormalities [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with Hy's law abnormalities [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with plasma HIV-1 RNA concentration <40 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with plasma HIV-1 RNA concentration <40 copies/mL [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with plasma HIV-1 RNA concentration <40 copies/mL [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in CD4+ and CD8+ cell counts [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in CD4+ and CD8+ cell counts [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in CD4+ and CD8+ cell counts [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Frequency and severity of adverse events and laboratory abnormalities [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in markers of immune activation (CD38 expression on CD4 and CD8 cells, C-reactive protein, D-dimer, transforming growth factor-beta [TGF-beta]) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in markers of immune activation (CD38 expression on CD4 and CD8 cells, C-reactive protein, D-dimer, transforming growth factor-beta [TGF-beta]) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in markers of immune activation (CD38 expression on CD4 and CD8 cells, C-reactive protein, D-dimer, transforming growth factor-beta [TGF-beta]) [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HCV RNA [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HCV RNA [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HCV RNA [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HBV DNA [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HBV DNA [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HBV DNA [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Enhanced Liver Fibrosis (ELF) test [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Enhanced Liver Fibrosis (ELF) test [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Enhanced Liver Fibrosis (ELF) test [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the hepatic elastography (FibroscanTM) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the hepatic elastography (FibroscanTM) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the hepatic elastography (FibroscanTM) [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in fibrosis score (Ishak) in liver biopsy samples at Week 144 (liver biopsy substudy) [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
  • Population pharmacokinetic analysis of time versus plasma concentration of maraviroc [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Exploratory exposure-response relationship, if any, between maraviroc PK and liver fibrosis biomarkers, any changes from baseline that may be observed in AST and ALT measurements or other laboratory measurements. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Health economic impact, as measured by the utilization of hepatic fibrosis and cirrhosis-related inpatient and outpatient services and associated costs of care. [ Time Frame: 144 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study Of Maraviroc In HIV Co-Infected Subjects With Hepatitis C And/Or Hepatitis B
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

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV Coinfection
  • 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
  • Drug: Placebo
    150mg, 300mg or 600mg twice daily x 144 weeks; dosing dependent on components of the current suppressive anti-HIV therapy
  • Experimental: 1.0
    Intervention: Drug: Maraviroc
  • Placebo Comparator: 2
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
138
March 2015
April 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Czech Republic,   France,   Germany,   Hungary,   Poland,   Puerto Rico,   Spain,   United Kingdom
 
NCT01327547
A4001098, 2010-021994-35
Yes
ViiV Healthcare
ViiV Healthcare
Pfizer
Study Director: Pfizer CT.gov Call Center Pfizer
ViiV Healthcare
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP