Multicenter, Safety Study Of Maraviroc

A Multicenter, Open Label, Non-Comparative Safety Study Of Maraviroc

To collect safety and tolerability data in a more diverse patient population of patients with HIV/Aids, who have limited therapeutic options.

Study Overview

• Status: Completed
• Conditions: Acquired Immunodeficiency Syndrome; HIV Infection
• Intervention / Treatment: Drug: Maraviroc

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 40110-160
      • Pfizer Investigational Site
  • DF
    • Brasilia, DF, Brazil, 70351-580
      • Pfizer Investigational Site
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Pfizer Investigational Site
  • PR
    • Curitiba, PR, Brazil, 80240-280
      • Pfizer Investigational Site
  • RJ
    • Nova Iguaçu, RJ, Brazil, 26030-380
      • Pfizer Investigational Site
  • RS
    • Porto Alegre, RS, Brazil, 90110-270
      • Pfizer Investigational Site
  • SC
    • Florianopolis, SC, Brazil, 88025-301
      • Pfizer Investigational Site
  • SP
    • Campinas, SP, Brazil, 13059-900
      • Pfizer Investigational Site
    • Campinas, SP, Brazil, 13083-887
      • Pfizer Investigational Site
    • Ribeirao Preto, SP, Brazil, 14048900
      • Pfizer Investigational Site
    • Santo Andre, SP, Brazil, 09060-650
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 01246-900
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 01307-001
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 04040-002
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 04121-000
      • Pfizer Investigational Site
    • São Paulo, SP, Brazil, 04231-030
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with limited or no approved treatment options available to them due to resistance or intolerance;
• Subjects must be failing to achieve adequate virologic suppression on their current regimen and have HIV-1 RNA ≥ 1000 copies/ml, at screening.
• Have only R5 HIV-1 at Screening as verified by the Monogram Biosciences Trofile assay.

Exclusion Criteria:

• Failed prior treatment with any CCR5 antagonist, in any ongoing CCR5 trials or having previously discontinued Maraviroc in trials
• Potentially life threatening (Grade 4) laboratory abnormality or medical condition (according to the Division of AIDS table for grading severity of adult adverse experiences) still under investigation unless a diagnosis has been established and felt not to affect risk/benefit assessment or eventual interpretation of safety results, based on discussion between the investigator and Pfizer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Maraviroc; Maraviroc should be dosed BID with total dose adjusted according to the other drugs the patient is taking. Maraviroc may be taken with or without food. The subject should only take missed doses if it is not within 6 hours prior to the planned next dose. No dose adjustment of OBT is required due to the presence of maraviroc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs: any untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was congenital anomaly. Grade 3: Events that interrupted participant's usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4: Events which were unacceptable and intolerable or which were irreversible or caused participant to be in imminent danger of death.	Baseline to 30 days post-week 96 or early termination (ET)
Number of Participants With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 and Grade 4 Laboratory Abnormalities	Grade 3 or severe events included those that interrupted participant's usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 or very severe events included those that were unacceptable and intolerable or which were irreversible or caused the participant to be in imminent danger of death.	Baseline to 30 days post-week 96 or ET
Number of Participants With Treatment Emergent Malignancies		Baseline to 30 days post-week 96 or ET
Number of Participants With Category C Acquired Immunodeficiency Syndrome (AIDS) Related Infections	Number of participants with AIDS-related infections based on investigator classification guided by a predefined list of clinical Category C AEs per Center for Disease Control (CDC) HIV Classification System.	Baseline to 30 days post-week 96 or ET
Number of Participants With Laboratory Test Abnormalities	Pre-defined criteria based on upper limit normal (ULN) and lower limit normal (LLN) were established for each laboratory test to define the values that would be identified as laboratory test abnormality.	Baseline to 30 days post-week 96 or ET

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 0.5 Log 10 Reduction in Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA)		Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or end of treatment (EOT)
Percentage of Participants With at Least 1.0 Log 10 Reduction in HIV-1 RNA		Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Percentage of Participants Achieving HIV-1 RNA Below Limit of Quantification	Below limit of quantification was defined as less than 400 copies/milliliter (mL)	Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 4, 8, 12, 24, 36, 48, 60, 72, 84 and Week 96 or EOT		Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 4, 8, 12, 24, 36, 48, 60, 72, 84 and Week 96 or EOT		Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Change From Baseline in CD4 Percent at Week 4, 8, 12, 24, 36, 48, 60, 72, 84 and Week 96 or EOT		Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Change From Baseline in CD8 Percent at Week 4, 8, 12, 24, 36, 48, 60, 72, 84 and Week 96 or EOT		Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Number of Participants With C-X-C Chemokine Receptor Type 4 {CXCR4} [X4] Tropism Status	Virus tropism was done by the Monogram Biosciences Trofile assay.	Time of virologic failure (VF) and Week 96 or EOT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Human Immunodeficiency Virus (HIV) -1 Viral Load (Ribonucleic Acid [RNA]) at Week 4, 8, 12, 24, 36, 48, 60, 72, 84 and Week 96 or EOT	Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter [log10 copies/ml]).	Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Time to Virologic Failure (VF)	Virologic failure was defined as failing to achieve a reduction in HIV-1 RNA of at least 0.5 log10 copies/ml from baseline by the second viral load determination; or experiencing at least 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline more than 0.5 log10 copies/ml; or experiencing an HIV-1 RNA more than 1000 copies/ml after having achieved an HIV-1 RNA below level of quantification.	Baseline to Week 96 or EOT
Number of Participants With Genotype Resistance	Evolution in resistance to OBT was shown by emergence of new primary or secondary resistance mutations to nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI).	Baseline through Week 96

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Furtado J, Madruga JV, Bicudo EL, da Eira M, Lopes MI, Netto EM, Santini-Oliveira M, Leite OH, Machado AA, Tupinambas U, de Andrade Neto JL, Lima MP, Pedro Rde J, Miranda AF, Lewi DS, Santos BR, Portsmouth S, Wajsbrot DB, Cassoli LM. Safety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study. AIDS Res Hum Retroviruses. 2013 Sep;29(9):1203-10. doi: 10.1089/AID.2012.0330. Epub 2013 Jun 25.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: May 22, 2007
• First Submitted That Met QC Criteria: May 22, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Estimate): September 9, 2011
• Last Update Submitted That Met QC Criteria: September 1, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Treatment Experienced; Multicenter; Open Label; Non-Comparative Safety Study Of Maraviroc
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: A4001063