CCR5 Inhibitor Treatment Intensification on CD4+ T-cell Recovery

NCT00925756 | Completed Phase 4 Results

• 1 other identifier: CCTG 590
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

CCTG 590 is a open-label study to evaluate the impact of therapy intensification with Maraviroc (MVC) (a CCR5 inhibitor) to a stable suppressive HIV antiretroviral regimen on the rate of CD4+ T-cell recovery and gene expression profiles. Patients on a stable first-line HIV regimen with continued viral suppression and sub-optimal CD4+ T-cell counts will be eligible for this study. Those who are found to be eligible will have MVC (dose-adjusted to background HIV regimen) added to their current HIV regimen for 24 weeks. After the 24 week intensification, the MVC will be discontinued, the original antiretroviral regimen will be continued and the subjects will be followed for an additional 12 weeks. The investigators hypothesize that MVC will improve the rate of CD4 recovery. This improved CD4 recovery will be associated with favorable changes in gene expression profiles of genes involved with CD4 maintenance and circulation.

Conditions

HIV Infections

Keywords

HIV; low CD4 recovery; Low CD4 recovery despite HIV control; Treatment experienced

Outcome Measures

Primary Outcomes (1)

• Differences in Gene Expression Profiles Obtained at Baseline and Week 4 and Week 24.

  To determine differential gene expression in T-Cells due to MVC exposure between week 0, 4 and 24 weeks. Repeated measures (RM) ANOVA was used to identify genes whose expression changed over the course of MVC administration. Multivariate permutation tests under default settings (80% confident no more than 10% false positives) were performed using BRB-Array Tools. Gene assignment to temporal profiles was performed using a non- parametric clustering algorithm in Short Time-series Expression Miner (STEM)

  Baseline to Week 24

Secondary Outcomes (2)

• CD4+ T-cell Absolute Count and Percentage at Baseline, Weeks 4 and 24.

  Baseline to Week 24

• Change in CD4+/CD8+ T-cell Immune Activation, Maturation, Regulatory and Apoptosis Markers at Baseline and Weeks 4 and 24.

  Baseline to Week 24

Study Arms (1)

Maraviroc 150 mg, 300 mg, or 600 mg twice daily

EXPERIMENTAL

This was a single arm study where Maraviroc was added for 24 weeks. Maraviroc was dose-adjusted for concomitantly administered HIV medications according to the manufacture's recommendations: 150 mg twice daily with strong CYP3A4 inhibitors, including: * Protease inhibitors (except tipranavir/ ritonavir) * Delavirdine * ketoconazole, itraconazole, clarithromycin, nefazadone, telithromycin * Darunavir/r + etravirine 300 mg twice daily with non-inducers/ non-inhibitors of CYP3A4, including: * Tipranavir/ ritonavir * Nevirapine * All NRTIs * Enfuvirtide 600 mg twice daily with strong CYP3A4 inducers, including: * Efavirenz, etravirine * rifampin

Drug: Maraviroc

Interventions

Maraviroc DRUG

Maraviroc will be given dose-adjusted to background HIV treatment (150 mg, 300 mg, or 600 mg twice daily)

Also known as: Selzentry

Maraviroc 150 mg, 300 mg, or 600 mg twice daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• All available CD4+ T cell counts within the last 12 months of screening below 350 cells/mm3 (minimum of 3 values obtained \> 30 days apart).
• HIV treatment with a stable (for at least 6 months) antiretroviral regimen consisting of at least 2 NRTIs and either a protease inhibitor boosted with low dose ritonavir or an NNRTI. A stable regimen is defined as no additions or deletions for more than 14 cumulative days.
• Patient considered to be receiving initial HIV regimen (history of medication substitution for toxicity is allowed).
• All available plasma HIV RNA levels within the last 12 months are below the level of detection. Isolated values that are detectable but \< 1000 copies will be allowed as long as the plasma HIV RNA levels before and after this detectable time point are undetectable - The subject should have a minimum of 3 values obtained \> 30 days apart.
• Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
• Men and women age ≥ 18 years.

You may not qualify if:

• Current antiretroviral regimen contains tenofovir disoproxil fumarate AND didanosine in combination.
• History of chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable).
• History of chronic active hepatitis B (defined as surface antibody negative, surface antigen positive and HBV DNA detectable).
• Concurrent use of G-CSF or GM-CSF.
• Prior or concurrent use of IL-2.
• Prior or concurrent use of a CCR5 inhibitor.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.
• Use of human growth hormone within 30 days prior to study entry.
• Initiation of testosterone or anabolic steroids within 30 days prior to study entry. (Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is allowed).
• Evidence of splenic sequestration or suppressed bone marrow function:
• Clinical or radiographic evidence of significant splenomegaly.
• History of leukemia or lymphoma.
• History of myelosuppressive chemotherapy or irradiation

Sponsors & Collaborators

• University of California, San Diego: lead
• University of California, Los Angeles: collaborator
• University of Southern California: collaborator
• Pfizer: collaborator
• California HIV/AIDS Research Program: collaborator

Study Sites (3)

University Southern California

Los Angeles, California, 90033, United States

Location

University California San Diego

San Diego, California, 92103, United States

Location

Harbor-UCLA

Torrance, California, 90502, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sheldon Morris
• Organization: UCSD

shmorris@ucsd.edu

6195438080

Study Officials

• Sheldon Morris, MD

  UC San Diego AntiViral Research Center (AVRC)

  STUDY CHAIR

• Richard Haubrich, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: June 22, 2009
• Study Start: October 20, 2008
• Primary Completion: May 2, 2012
• Study Completion: April 11, 2014
• Last Updated: August 19, 2020
• Results First Posted: August 19, 2020

Record last verified: 2020-08

Locations

US (3)