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Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure

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ClinicalTrials.gov Identifier: NCT00735072
Recruitment Status : Completed
First Posted : August 14, 2008
Results First Posted : July 18, 2012
Last Update Posted : July 18, 2012
Sponsor:
Collaborators:
Pfizer
amfAR, The Foundation for AIDS Research
Stanford University
Case Western Reserve University
Rush University
Information provided by (Responsible Party):
University of California, San Francisco

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition HIV Infection
Interventions Drug: Placebo
Drug: Maraviroc
Enrollment 45
Recruitment Details Subjects were recruited from the HIV clinics at San Francisco General Hospital, Stanford University, Case Western Reserve University, and Rush University/CORE Center between September, 2008, and December, 2009.
Pre-assignment Details All 45 enrolled patients were assigned to study intervention. We over-enrolled by 3 subjects given 2 premature treatment discontinuations and one subject with unavailable baseline peripheral blood mononuclear cell (PBMC) samples available for analysis.
Arm/Group Title Maraviroc Placebo
Hide Arm/Group Description Maraviroc (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens). Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
Period Title: Overall Study
Started 23 22
Completed 22 21
Not Completed 1 1
Reason Not Completed
interrupted study med during ARV change             1             0
Subject interrupted ARVs (non-adherence)             0             1
Arm/Group Title Maraviroc Placebo Total
Hide Arm/Group Description Maraviroc (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens). Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens). Total of all reporting groups
Overall Number of Baseline Participants 23 22 45
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 45 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
 100.0%
21
  95.5%
44
  97.8%
>=65 years
0
   0.0%
1
   4.5%
1
   2.2%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 22 participants 45 participants
50  (8) 50  (10) 50  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 45 participants
Female
0
   0.0%
2
   9.1%
2
   4.4%
Male
23
 100.0%
20
  90.9%
43
  95.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 23 participants 22 participants 45 participants
23 22 45
1.Primary Outcome
Title Week 24 Change in Percentage of CD8+ T Cells That Co-express CD38 and HLA DR (Week 24 %CD38+HLA-DR+ CD8+ T Cells Minus Baseline %CD38+HLA-DR+ CD8+ T Cells)
Hide Description [Not Specified]
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Maraviroc Placebo
Hide Arm/Group Description:
Maraviroc (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
Overall Number of Participants Analyzed 23 22
Median (Inter-Quartile Range)
Unit of Measure: %CD38+ HLA-DR+ CD8+ T cells
2.2
(-0.6 to 4.1)
-0.7
(-3.5 to 0.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc, Placebo
Comments Null hypothesis: there will be no difference in the week 24 change in %activated CD8+ T cells between arms. Assuming a standard deviation as high as 3.5% and a Type I error of 5%, with 21 subjects in each treatment arm we would have 80% statistical power to detect a mean 3 percentage-point difference in the percent of activated CD8+ T cells between the active drug and placebo groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Change in CD4+ T Cell Count
Hide Description [Not Specified]
Time Frame Week 24
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay)
Hide Description [Not Specified]
Time Frame Week 24
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only)
Hide Description [Not Specified]
Time Frame Week 24
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only)
Hide Description [Not Specified]
Time Frame Week 24
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Maraviroc Placebo
Hide Arm/Group Description Maraviroc (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens). Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
All-Cause Mortality
Maraviroc Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Maraviroc Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/23 (0.00%)   0/22 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Maraviroc Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   4/23 (17.39%)   2/22 (9.09%) 
Hepatobiliary disorders     
Indirect Hyperbilirubinemia (on atazanavir-based ART)  [1]  2/23 (8.70%)  1/22 (4.55%) 
HBV flare, transaminitis  [2]  0/23 (0.00%)  1/22 (4.55%) 
Infections and infestations     
Prolonged Fever * [3]  1/23 (4.35%)  0/22 (0.00%) 
Metabolism and nutrition disorders     
Triglyceride Elevation  [4]  1/23 (4.35%)  0/22 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
All cases were comparable to baseline values and all were on atazanavir-based regimens. None required treatment change during the trial.
[2]
Subject stopped all ARVs and study medications due to a lapse in insurance coverage (and didnt notify physician or study team). Had a recurrence of HBV viremia with transaminitis (after discontinuing study medication), resolved after restarting ART.
[3]
Unexplained fever for 2 weeks without identifiable cause, resolved in absence of any specific therapy and subject had continued study medication without recurrence.
[4]
Grade 3 trygliceride elevation noted, comparable to recent values prior to enrollment and resolved to baseline values without change in therapy.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Peter W. Hunt, MD
Organization: UCaliforniaSF
Phone: (415) 476-4082 ext 345
EMail: phunt@php.ucsf.edu
Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00735072     History of Changes
Other Study ID Numbers: GA9001DE
First Submitted: August 12, 2008
First Posted: August 14, 2008
Results First Submitted: June 5, 2011
Results First Posted: July 18, 2012
Last Update Posted: July 18, 2012