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

NCT00098306 | Completed Phase 2 Results DMC

• 1 other identifier: A4001027
• Study Type: interventional
• Target: 601
• Locations: 2 countries
• Sites: 22

Brief Summary

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor 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, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The purpose of this study is to evaluate the antiretroviral activity of maraviroc (UK-427,857) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and are infected with R5-tropic virus exclusively. This study will involve more than 100 centers from the US and Canada to achieve a total randomized subject population of 500 subjects. Patients will be randomly (2:2:1) 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. The study will enroll over approximately a 9 month period with 48 weeks of treatment. This may be extended for an additional year depending on the results at 48 weeks. 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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

• Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline

  Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

  Baseline

• Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24

  Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

  Baseline and Week 24

• Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48

  Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization and immediately pre-dose.

  Baseline and Week 48

Secondary Outcomes (15)

• Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL

  Week 24 and 48

• Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 0.5 log10 Decrease From Baseline

  Week 24 and 48

• Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 1.0 log10 Decrease From Baseline

  Week 24 and 48

• Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL

  Week 24 and 48

• Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline

  Baseline

Study Arms (3)

1

EXPERIMENTAL

Drug: Maraviroc (UK-427,857); Drug: Optimized Background Therapy

2

EXPERIMENTAL

Drug: Optimized Background Therapy; Drug: Placebo

3

EXPERIMENTAL

Drug: Optimized Background Therapy

Interventions

Maraviroc (UK-427,857) DRUG

Maraviroc was given either once or twice per day with the dose adjusted according to the optimized background therapy

Also known as: Selzentry

1

Optimized Background Therapy DRUG

Maraviroc was given either once or twice per day with the dose adjusted according to the optimized background therapy

1

Placebo DRUG

Patients will be randomly (2:2:1) 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.

2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 three of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 6 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, two protease inhibitors (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

You may not qualify if:

• 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 judgement, 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, hepatoxic 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• Pfizer: collaborator

Study Sites (22)

Pfizer Investigational Site

Sacramento, California, 95825, United States

Location

Pfizer Investigational Site

San Francisco, California, 94115, United States

Location

Pfizer Investigational Site

San Francisco, California, 94118, United States

Location

Pfizer Investigational Site

San Francisco, California, 94121, United States

Location

Pfizer Investigational Site

Auroa, Colorado, 80045, United States

Location

Pfizer Investigational Site

Aurora, Colorado, 80045, United States

Location

Pfizer Investigational Site

Washington D.C., District of Columbia, 20036, United States

Location

Pfizer Investigational Site

Tampa, Florida, 33602, United States

Location

Pfizer Investigational Site

Tampa, Florida, 33614, United States

Location

Pfizer Investigational Site

Vero Beach, Florida, 32960, United States

Location

Pfizer Investigational Site

Atlanta, Georgia, 30308, United States

Location

Pfizer Investigational Site

New Orleans, Louisiana, 70112, United States

Location

Pfizer Investigational Site

Santa Fe, New Mexico, 87505, United States

Location

Pfizer Investigational Site

New York, New York, 10003, United States

Location

Pfizer Investigational Site

Rochester, New York, 14642, United States

Location

Pfizer Investigational Site

The Bronx, New York, 10467, United States

Location

Pfizer Investigational Site

Cincinnati, Ohio, 45267-0405, United States

Location

Pfizer Investigational Site

Portland, Oregon, 97219, United States

Location

Pfizer Investigational Site

Austin, Texas, 78705, United States

Location

Pfizer Investigational Site

Annandale, Virginia, 22003, United States

Location

Pfizer Investigational Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Pfizer Investigational Site

Montreal, Quebec, H2L 4P9, Canada

Location

Related Publications (5)

• Lewis ME, Simpson P, Mori J, Jubb B, Sullivan J, McFadyen L, van der Ryst E, Craig C, Robertson DL, Westby M. V3-Loop genotypes do not predict maraviroc susceptibility of CCR5-tropic virus or clinical response through week 48 in HIV-1-infected, treatment-experienced persons receiving optimized background regimens. Antivir Chem Chemother. 2021 Jan-Dec;29:20402066211030380. doi: 10.1177/20402066211030380.

  PMID: 34343443 DERIVED

• Gulick RM, Fatkenheuer G, Burnside R, Hardy WD, Nelson MR, Goodrich J, Mukwaya G, Portsmouth S, Heera JR. Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):78-81. doi: 10.1097/QAI.0b013e3182a7a97a.

  PMID: 24419064 DERIVED

• Hardy WD, Gulick RM, Mayer H, Fatkenheuer G, Nelson M, Heera J, Rajicic N, Goodrich J. Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2. J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):558-64. doi: 10.1097/QAI.0b013e3181ee3d82.

  PMID: 20703158 DERIVED

• Fatkenheuer G, Nelson M, Lazzarin A, Konourina I, Hoepelman AI, Lampiris H, Hirschel B, Tebas P, Raffi F, Trottier B, Bellos N, Saag M, Cooper DA, Westby M, Tawadrous M, Sullivan JF, Ridgway C, Dunne MW, Felstead S, Mayer H, van der Ryst E; MOTIVATE 1 and MOTIVATE 2 Study Teams. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med. 2008 Oct 2;359(14):1442-55. doi: 10.1056/NEJMoa0803154.

  PMID: 18832245 DERIVED

• Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, Dunne MW, van der Ryst E, Mayer H; MOTIVATE Study Teams. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008 Oct 2;359(14):1429-41. doi: 10.1056/NEJMoa0803152.

  PMID: 18832244 DERIVED

Related Links

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

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: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2004
• First Posted: December 7, 2004
• Study Start: November 1, 2004
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2011
• Last Updated: April 27, 2012
• Results First Posted: April 27, 2012

Record last verified: 2012-04

Locations

CA (2); US (20)