A4001095: A Multicenter, Randomized, Double-Blind, Comparative Trial of Maraviroc + Darunavir/Ritonavir Versus Emtricitabine/Tenofovir + Darunavir/Ritonavir for the Treatment of Antiretroviral-naive HIV-Infected Patients with CCR5-Tropic HIV-1

Study ID
STU 072011-090

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Minerva Santos
214-590-2794
minerva.santos@utsouthwestern.edu

Principal Investigator
Mamta Jain

Summary

This is a 96-week, multicenter, international, double-blind, randomized, comparative, phase 3 study to assess the safety and efficacy of maraviroc (150 mg QD) in combination with darunavir/ritonavir (800/100 mg QD) versus emtricitabine/tenofovir (Truvada) 200/300 mg QD in combination with darunavir/ritonavir (800/100 mg QD) in
antiretroviral-naive subjects infected with CCR5 co-receptor-tropic (R5) HiV-1. This study will enroll a total of 804 subjects (402 subjects/treatment arm) and will be conducted at approximately 250 sites in approximately 20 countries.

Participants that decide to participate in this study will be assigned to 1 of the 2 groups:

* Maraviroc + Darunavir/Ritonavir + Placebo once a day
* emtricitabine/Tenofovir + Darunavir/Ritonavir + Placebo once a day

Primary endpoint:
The proportion of subjects with plasma HiV-1 Rna [Less Than]50 copies/mL at Week 48.

Secondary endpoints:
The following secondary endpoints will be evaluated:
1. Safety: Frequency, severity and relationship of adverse events to test drug; serious adverse events; discontinuations due to adverse events frequency and severity of abnormal laboratory values.
2. The relationship between the proportion of subjects with plasma HiV-1 Rna [Less Than]50 copies/mL at the Week 48 and Week 96 visits and the screening tropism test (Genotype test or eSTa) in the maraviroc-containing regimen.
3. Virologic Response: Proportion of subjects with plasma HiV-Rna [Less Than]50 copies/mL at Week 96.
4. immunological Response at Week 48 and Week 96:
a. Changes in CD4+ T-lymphocyte (CD4) cell counts and percent change from Baseline;
b. Changes in CD8+ T-lymphocyte (CD8) cell counts and percent change from Baseline;
c. Changes in CD4+/CD8+ ratio and changes from Baseline.
5. evolution of viral resistance and tropism change between Screening or Baseline and the time of confirmation of virologic failure or the last on-treatment time point:
a. HiV-1 tropism (Genotype test)
b. For virologic failure with R5 virus, viral resistance to maraviroc (maraviroc-treated subjects only).
c. Viral resistance (Genotype and Phenotype) to nucleoside/nucleotide reverse transcriptase inhibitors (nRTi) and
non-nucleoside reverse transcriptase inhibitors (nnRTi) [reverse transcriptase inhibitors, RTi] and protease
inhibitors (Pi).
6. Changes in peripheral fat distribution and trunk to limb fat ratio (using DeXa scan) from Baseline and at Weeks 48 and 96 (approximately109 subjects per treatment arm).
7. Changes in bone mineral density (using DeXa scan and serum markers) from Baseline and at Weeks 48 and 96 (approximately 109 subjects per treatment arm).

Participant Eligibility

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study

2. At least 18 years of age at the Screening Visit.

3. Plasma HIV-1 RNA > or equal to 1,000 copies/mL measured at the Screening Visit.

4. CD4 count > or equal to 100 cells/mm3 at Screening.

5. Have only R5 HIV-1 at Screening as verified by a randomized tropism assay.

6. A negative urine pregnancy test at Screening and at the Baseline Visit, prior to receiving the first dose of study medication, for Women of Child Bearing Potential (WOCBP).

NOTE: WOCBP include any female who has experienced menarche and who has not undergone hysterectomy, bilateral oophorectomy or tubal ligation or any other successful surgical sterilization or is not post-menopausal (age >45 years, amenorrheic for >2 years, and serum FSH levels >30 IU/L). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products (intrauterine devices; barrier methods: eg. condom or diaphragm with spermicidal) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (eg, vasectomy), should be considered to be of child bearing potential.

7. WOCBP, male study subjects and their partners must use two forms of contraception one of which is effective barrier contraception throughout the study and for at least 28 days following the last dose of study medication. WOCBP must use another acceptable method of contraception from screening to at least 28 days after the trial.

Acceptable contraception includes the following:
- Oral, transdermal, implantable, or injectable hormone therapy;
- Effective intrauterine devices;
- Vasectomized partner;
- Double barrier contraceptive methods.

8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

9. Subjects who have consented to participate in the DEXA scan sub-study must be
< or equal to 136 kg (300 lb) in weight and < or equal to 1.95 m (6ft. 4.8 inches) in height and have a body mass index < or equal to 40 kg/m2.