Expanded Access Program for Maraviroc At Multiple Centers

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Open Label, Expanded Access Trial Of Maraviroc

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: maraviroc


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: maraviroc<br>* The nominal dose for maraviroc is 300 mg twice a day (BID). However, the dosage of maraviroc should be adjusted based on optimal background therapy (OBT) patient is taking. If OBT includes CYP3A4 inhibitor (with or without inducers) maraviroc dose should be 150 mg BID and if OBT includes CYP3A4 inducer (without inhibitors) maraviroc dose should be 600mg BID. If OBT does not include any CYP3A4 inducers or inhibitors maraviroc dose should be 300 mg BID.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | 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. | Baseline up to Week 144 | 
| Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | 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. | Baseline up to Week 144 | 
| Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | 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. | Baseline up to Week 144 | 
| Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | 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. | Baseline up to Week 144 | 
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline Viral Load |  | Baseline up to Week 144 | 
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline/Nadir CD4 Cell Counts |  | Baseline up to Week 144 | 
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Time on Therapy |  | Baseline up to Week 144 | 
| Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender | Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication. | Baseline up to Week 144 | 
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication. | Baseline up to Week 144 | 
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication. | Baseline up to Week 144 | 
| Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose. | Baseline up to Week 144 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | 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. | Baseline up to Week 144 | 
| Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | 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. | Baseline up to Week 144 | 
| Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | 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. | Baseline up to Week 144 | 
| Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | 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. | Baseline up to Week 144 | 
| Change From Baseline in CD4 Cell Count | 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. | Baseline up to Week 144 | 
| Change From Baseline in CD4 Cell Count Percent | Change from baseline in CD4 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value. | Baseline up to Week 144 | 
| Change From Baseline in CD8 Cell Count | 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. | Baseline up to Week 144 | 
| Change From Baseline in CD8 Cell Count Percent | Change from baseline in CD8 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value. | Baseline up to Week 144 | 
| Median Time to Virologic Failure | 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. | Day 1 up to Week 144 | 
| Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | 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. | Baseline up to Week 144 | 
| Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | 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. | Screening up to Week 144 | 
| 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 Plateau | 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. | Baseline up to Week 144 | 
| Number of Participants With Emergence of Resistance to Maraviroc as Defined by Genotypic Changes in the V3 Loop of Glycoprotein 120 (gp 120) | 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. | Baseline up to Week 144 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections