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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00098748




Registration number
NCT00098748
Ethics application status
Date submitted
7/12/2004
Date registered
8/12/2004
Date last updated
7/12/2010

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
A4001029
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Optimized Background Therapy (OBT)
Treatment: Drugs - maraviroc (UK-427,857)
Treatment: Drugs - Optimized Background Therapy (OBT)
Treatment: Drugs - maraviroc (UK-427,857)
Treatment: Drugs - Optimized Background Therapy (OBT)

Experimental: 1 -

Experimental: 2 -

Experimental: 3 -


Treatment: Drugs: Optimized Background Therapy (OBT)
OBT (3-6 drugs based on treatment history and resistance testing)

Treatment: Drugs: maraviroc (UK-427,857)
maraviroc (UK-427,857) 150 mg taken once daily

Treatment: Drugs: Optimized Background Therapy (OBT)
OBT (3-6 drugs based on treatment history and resistance testing)

Treatment: Drugs: maraviroc (UK-427,857)
maraviroc (UK-427,857) 150 mg taken twice daily

Treatment: Drugs: Optimized Background Therapy (OBT)
OBT (3-6 drugs based on treatment history and resistance testing)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) - Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter [log10 copies/mL]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [1] 0 0
Baseline to Week 24 and Week 48
Secondary outcome [1] 0 0
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL
Timepoint [1] 0 0
Week 24, Week 48
Secondary outcome [2] 0 0
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels - Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [2] 0 0
Baseline, Week 24, Week 48
Secondary outcome [3] 0 0
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels - Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [3] 0 0
Baseline, Week 24, Week 48
Secondary outcome [4] 0 0
Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL
Timepoint [4] 0 0
Baseline, Week 24, Week 48
Secondary outcome [5] 0 0
Change From Baseline in CD4 Cell Count - Change from baseline in CD4 cell count (measured as cells per microliter [cells/µL]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [5] 0 0
Baseline to Week 24 and Week 48
Secondary outcome [6] 0 0
Change From Baseline in CD8 Cell Count - Change from baseline in CD8 cell count (measured as cells/µL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [6] 0 0
Baseline to Week 24 and Week 48
Secondary outcome [7] 0 0
Time (50% Quartile Point Estimate) to Virologic Failure - Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug [perm DC]; lost to follow-up [LTFU]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not <400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level <400 copies/mL (on 2 consecutive visits); failure if level =400 copies/mL (2 consecutive visits) or 1 visit =400 copies/mL followed by perm DC or LTFU.
Timepoint [7] 0 0
Day 1 through Week 24 and through Week 48
Secondary outcome [8] 0 0
Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA - Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as [AUC of HIV-1 RNA viral load (log10 copies/mL) / time period] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Timepoint [8] 0 0
Baseline to Week 24 and Week 48
Secondary outcome [9] 0 0
Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure - Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, >4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility.
Timepoint [9] 0 0
Baseline through Week 48
Secondary outcome [10] 0 0
Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) - Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Timepoint [10] 0 0
Screening through Week 24
Secondary outcome [11] 0 0
Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) - Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Timepoint [11] 0 0
Screening through Week 48
Secondary outcome [12] 0 0
Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening - Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, >4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Timepoint [12] 0 0
Screening, Week 24
Secondary outcome [13] 0 0
Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening - Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or =3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Timepoint [13] 0 0
Screening, Week48
Secondary outcome [14] 0 0
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) - Number of subjects with 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 7 days after last dose of study drug.
Timepoint [14] 0 0
Baseline through Week 24
Secondary outcome [15] 0 0
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) - Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Timepoint [15] 0 0
Baseline through Week 48

Eligibility
Key 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
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Surry Hills
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Herston
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Carlton
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Surry Hills
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3053 - Carlton
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New Mexico
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Belgium
State/province [17] 0 0
Liege
Country [18] 0 0
Canada
State/province [18] 0 0
Manitoba
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Koeln
Country [24] 0 0
Netherlands
State/province [24] 0 0
Utrecht
Country [25] 0 0
Spain
State/province [25] 0 0
Alicante
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Cordoba
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Switzerland
State/province [29] 0 0
Zürich
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Brighton
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Edinburgh
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Pfizer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00098748
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications