MedPath

Expanded Access Program for Maraviroc At Multiple Centers

Phase 3
Completed
Conditions
HIV Infections
Interventions
Registration Number
NCT00426660
Lead Sponsor
ViiV Healthcare
Brief Summary

To provide access to maraviroc to patients who have limited or no therapeutic treatment options and to collect more safety data in a broader patient population.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1047
Inclusion Criteria
  • Subjects must be failing to achieve adequate virologic suppression on their current regimen and have HIV-1 RNA greater than or equal to 1000 copies/ml, at screening
  • Have only R5 HIV-1 at Screening as verified by the Monogram Biosciences Trofile assay
  • Minimum age must be 16 years or minimum adult age as determined by local regulatory authorities or directed by local law.
Exclusion Criteria
  • Failed prior treatment with any CCR5 antagonist, in any ongoing CCR5 trial or having previously prematurely discontinued Maraviroc in trials

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
1maraviroc-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE)Baseline up to Week 144

AEs as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3 = severe: interrupted usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 = very severe: events that were unacceptable and intolerable or were irreversable or caused imminent danger of death. If same participant had more than 1 occurrence in the same preferred term event category, only the most severe (grade 4) occurrence was taken. Treatment-related = investigator assessment of a reasonable possibility that the investigational product caused or contributed to the AE.

Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline AbnormalitiesBaseline up to Week 144

Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3, Severe =events that interrupted participants usual daily activity and traditionally required systemic drug therapy or other treatment.

Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline AbnormalitiesBaseline up to Week 144

Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 4, Very Severe = events which were unacceptable and intolerable or were irreversible or caused the participant to be in imminent danger of death.

Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining IllnessesBaseline up to Week 144

Treatment-emergent AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C adverse events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 30 days after last dose of study drug.

Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline Viral LoadBaseline up to Week 144
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline/Nadir CD4 Cell CountsBaseline up to Week 144
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Time on TherapyBaseline up to Week 144
Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by GenderBaseline up to Week 144

Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Adverse Events (AEs) by RaceBaseline up to Week 144

Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Adverse Events (AEs) by AgeBaseline up to Week 144

Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology StatusBaseline up to Week 144

Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA)Baseline up to Week 144

Defined as HIV-1 RNA levels \< 400 Copies/mL or at least 0.5 Log 10-decrease from baseline in HIV-1 RNA levels.

Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.

Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNABaseline up to Week 144

Defined as HIV-1 RNA levels \< 400 copies/mL or at least 1.0 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.

Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mLBaseline up to Week 144

Limit of quantification defined as \<400 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.

Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mLBaseline up to Week 144

Limit of quantification defined as \<50 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.

Change From Baseline in CD4 Cell CountBaseline up to Week 144

Change from baseline in cluster of differentiation 4 helper T cells (CD4) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.

Change From Baseline in CD4 Cell Count PercentBaseline up to Week 144

Change from baseline in CD4 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.

Change From Baseline in CD8 Cell CountBaseline up to Week 144

Change from baseline in cluster of differentiation 8 suppressor T cells (CD8) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.

Change From Baseline in CD8 Cell Count PercentBaseline up to Week 144

Change from baseline in CD8 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.

Median Time to Virologic FailureDay 1 up to Week 144

Computed as time from the first dose of study medication to the loss of virologic response. Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥ 0.5 log10 copies /mL by the second viral load determination (unless viral load was below the lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving a HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.

Number of Participants With Reduced Maraviroc Susceptibility as Defined by Change From Baseline to Time of Virologic Failure in Inhibitory Concentration of 50% (IC 50) and Presence of PlateauBaseline up to Week 144

Resistance to maravroc in viruses from participants failing therapy with R5 virus was investigated using the in vitro phenotypic (drug susceptibility) assay. The number of participants who failed with R5 virus were assessed successfully for maraviroc susceptibility at Baseline and Last on--treatment (Week 144). Samples were analyzed for change from Baseline to time of virologic failure in IC 50 and presence of plateau. A maximal percent inhibition (MPI) \<95% established as a plateau in inhibition at high concentrations of maraviroc was used to identify viruses which had reduced phenotypic susceptibility to maraviroc.

Number of Participants With Emergence of Resistance to Maraviroc as Defined by Genotypic Changes in the V3 Loop of Glycoprotein 120 (gp 120)Baseline up to Week 144

Virus from participants who experienced virologic failure was analyzed for resistance to maraviroc. Resistance testing was performed on archived samples of participants which were available pre--treatment at time of virologic failure. For participants who met definition of virologic failure during the trial, the sequencing of the V3 loop of HIV--1 viral envelope gp 120 was evaluated to identify any amino acid changes concomitant with decreased susceptibility to maraviroc.

Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic FailureBaseline up to Week 144

Reasons for virologic failure: A) failure to achieve a reduction in HIV-1 RNA\>=0.5 log10 copies/ml from baseline (BL) by second viral load determination (unless below level of quantification \[LOQ\]); B) \>=0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from BL \>0.5 log10 copies/ml ; C) HIV-1 RNA \>1000 copies/ml after having achieved an HIV-1 RNA below LOQ.

Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic FailureScreening up to Week 144

Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable \[NR\]) at Screening (Scr) and time of virologic failure (V fail). Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥0.5 log10 copies/mL by second viral load determination (unless viral load was below lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.

Trial Locations

Locations (350)

The University of Alabama

🇺🇸

Birmingham, Alabama, United States

Health Services Center

🇺🇸

Hobson City, Alabama, United States

El Rio, Special Immunology Associates

🇺🇸

Tucson, Arizona, United States

Health for Life Clinic PLLC

🇺🇸

Little Rock, Arkansas, United States

Thomas T Jefferson, MD

🇺🇸

Little Rock, Arkansas, United States

Vista Medical

🇺🇸

Beverly Hills, California, United States

AHF Research Center

🇺🇸

Beverly Hills, California, United States

Orange County Center for Special Immunology

🇺🇸

Fountain Valley, California, United States

Kaiser Permanente

🇺🇸

Jonesboro, Georgia, United States

Living Hope Clinical Trials

🇺🇸

Long Beach, California, United States

Scroll for more (340 remaining)
The University of Alabama
🇺🇸Birmingham, Alabama, United States

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