Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects

NCT00098748

Last updated date
Study Location
Pfizer Investigational Site
Birmingham, Alabama, 35294, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
HIV Infections
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
16 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)

- HIV-1 RNA viral load of greater than or equal to 5,000 copies/mL

- Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks

- Documented genotypic or phenotypic resistance to two of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 3 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor (excluding low-dose ritonavir) and/or enfuvirtide

- Be willing to remain on randomized treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure

- A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)

- Effective barrier contraception for WOCBP and males

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Patients requiring treatment with more than 6 antiretroviral agents (excluding
low-dose ritonavir)


- Prior treatment with maraviroc (UK-427,857) or another experimental HIV entry
inhibitor for more than 14 days


- Suspected or documented active, untreated HIV-1 related opportunistic infection (OI)
or other condition requiring acute therapy


- Treatment for an active opportunistic infection, or unexplained temperature >38.5
degrees Celsius for 7 consecutive days


- Active alcohol or substance abuse sufficient, in the Investigator's judgment, to
prevent adherence to study medication and/or follow up


- Lactating women, or planned pregnancy during the trial period


- Significant renal insufficiency


- Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or
cytotoxic agent within 30 days prior to randomization or the expected need for such
therapy during the study period


- Documented or suspected acute hepatitis or pancreatitis within 30 days prior to
randomization


- Significantly elevated liver enzymes or cirrhosis


- Significant neutropenia, anemia or thrombocytopenia


- Malabsorption or an inability to tolerate oral medications


- Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease


- Certain medications


- Malignancy requiring parenteral chemotherapy that must be continued for the duration
of the trial


- R5 virus phenotype only


- No option to use at least one non-nucleoside reverse transcriptase inhibitor or
protease inhibitor, or enfuvirtide, based on resistance testing


- Any other clinical condition that, in the Investigator's judgment, would potentially
compromise study compliance or the ability to evaluate safety/efficacy

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Advanced Information
Descriptive Information
Brief Title  ICMJE Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects
Official Title  ICMJE A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial of a Novel CCR5 Antagonist, UK-427,857, in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced, Non CCR5-Tropic HIV-1 Infected Subjects
Brief Summary Maraviroc (UK-427,857), a selective and reversible CCR5 co-receptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients in the United States, maraviroc (UK-427,857) is approved for use as part of combination antiretroviral treatment in treatment-experienced and treatment-naive adult subjects. At least 50% of treatment-experienced patients are infected with R5-tropic HIV-1 exclusively. However, even in patients infected with a dual tropic (R5 + X4) phenotype, a large proportion of the virus population still uses CCR5 exclusively. Thus, the purpose of this study is to evaluate the antiretroviral activity, and safety, of maraviroc (UK-427,857) (in combination with other agents) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and not infected with R5-tropic virus exclusively. This study will involve more than 200 centers globally to achieve a total randomized subject population of 192 subjects. Patients will be randomly (1:1:1) assigned to one of three groups: Optimized Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. Randomization was stratified by Enfuvirtide use in OBT (yes/no) and Screening HIV-1 RNA level (viral load) (<100,000/? 100, 000 copies per milliliter [copies per mL]). The study will enroll over approximately a 9 month period with 48 weeks of treatment. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 24 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will also be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24 and 48.
Detailed Description

(i) Subjects remained on their assigned therapy for 48 weeks, unless the subject was discontinued early for protocol-defined treatment failure or other reasons such as adverse event, loss to follow-up, withdrawal of consent, or death.

(ii) If a subject met the criteria for treatment failure or discontinued for another reason (eg, pregnancy, adverse event) and required an alternative regimen, the subject was followed until the Week 48 visit according to protocol guidelines. The new regimen, selected by the Investigator based on the results of resistance testing at the time of failure, had to be recorded in the CRF.

(iii) Open-label maraviroc (UK-427,857) was provided by the sponsor, until it was commercially available, to subjects who completed 48 weeks of therapy and for whom it was medically appropriate to continue therapy with maraviroc (UK-427,857).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Optimized Background Therapy (OBT)
    OBT (3-6 drugs based on treatment history and resistance testing)
  • Drug: maraviroc (UK-427,857)
    maraviroc (UK-427,857) 150 mg taken once daily
    Other Name: Selzentry, Celsentri
  • Drug: maraviroc (UK-427,857)
    maraviroc (UK-427,857) 150 mg taken twice daily
    Other Name: Selzentry, Celsentri
Study Arms  ICMJE
  • Experimental: 1
    Interventions:
    • Drug: Optimized Background Therapy (OBT)
    • Drug: maraviroc (UK-427,857)
  • Experimental: 2
    Interventions:
    • Drug: Optimized Background Therapy (OBT)
    • Drug: maraviroc (UK-427,857)
  • Experimental: 3
    Intervention: Drug: Optimized Background Therapy (OBT)
Publications * Saag M, Goodrich J, Fätkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, Mayer H; A4001029 Study Group. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009 Jun 1;199(11):1638-47. doi: 10.1086/598965.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 14, 2010)
190
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date December 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)
  • HIV-1 RNA viral load of greater than or equal to 5,000 copies/mL
  • Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks
  • Documented genotypic or phenotypic resistance to two of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 3 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor (excluding low-dose ritonavir) and/or enfuvirtide
  • Be willing to remain on randomized treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure
  • A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)
  • Effective barrier contraception for WOCBP and males

Exclusion Criteria:

  • Patients requiring treatment with more than 6 antiretroviral agents (excluding low-dose ritonavir)
  • Prior treatment with maraviroc (UK-427,857) or another experimental HIV entry inhibitor for more than 14 days
  • Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy
  • Treatment for an active opportunistic infection, or unexplained temperature >38.5 degrees Celsius for 7 consecutive days
  • Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up
  • Lactating women, or planned pregnancy during the trial period
  • Significant renal insufficiency
  • Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period
  • Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization
  • Significantly elevated liver enzymes or cirrhosis
  • Significant neutropenia, anemia or thrombocytopenia
  • Malabsorption or an inability to tolerate oral medications
  • Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease
  • Certain medications
  • Malignancy requiring parenteral chemotherapy that must be continued for the duration of the trial
  • R5 virus phenotype only
  • No option to use at least one non-nucleoside reverse transcriptase inhibitor or protease inhibitor, or enfuvirtide, based on resistance testing
  • Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Germany,   Netherlands,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00098748
Other Study ID Numbers  ICMJE A4001029
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Director, Clinical Trial Disclosure Group, Pfizer, Inc.
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account ViiV Healthcare
Verification Date November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP