Safety, Efficacy and Dose-response Study of BMS-986001 in Subjects With HIV-1 Infection Who Are Treatment-naive

Study Overview
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Brief Summary
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The purpose of this study is to identify at least one dose of BMS-986001 which is safe, well tolerated, and efficacious when combined with Efavirenz (EFV) + Lamivudine (3TC) for treatment-naive Human Immunodeficiency Virus 1 (HIV-1) infected subjects

Detailed Description
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Double Blind through Week 24. Partially Blind (to subjects, caregivers, Investigators) through Week 48.

Official Title
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A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: BMS-986001
* Drug: BMS-986001
* Drug: BMS-986001
* Drug: Placebo matching with BMS-986001
* Drug: Efavirenz
* Drug: Lamivudine
* Drug: Tenofovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age, (or minimum age as determined by local regulatory or as legal requirements dictate, whichever is higher) Plasma HIV-1 RNA > 5000 copies/mL Antiretroviral treatment-naive; defined as no current or previous exposure to > 1 week of an antiretroviral drug CD4+ T-cell count > 200 cells/mm3 Exclusion Criteria: Resistance to any of the study medications [Tenofovir Disoproxil Fumarate(TDF), Efavirenz (EFV), Lamivudine (3TC)] or to HIV Protease Inhibitors (PIs) Contraindications to any of the study drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: BMS-986001 (100 mg) + Placebo + Efavirenz + Lamivudine<br> | Drug: BMS-986001<br>* Capsules, Oral, 100 mg, Once daily, At least 48 weeks<br>Drug: Placebo matching with BMS-986001<br>* Capsules, Oral, 0 mg, Once daily, At least 48 weeks<br>Drug: Efavirenz<br>* Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase<br>* Other names: Sustiva®;Drug: Lamivudine<br>* Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase<br>* Other names: Epivir®;|
| Experimental: Arm 2: BMS-986001 (200 mg) + Placebo + Efavirenz + Lamivudine<br> | Drug: BMS-986001<br>* Capsules, Oral, 200 mg, Once daily, At least 48 weeks<br>Drug: Placebo matching with BMS-986001<br>* Capsules, Oral, 0 mg, Once daily, At least 48 weeks<br>Drug: Efavirenz<br>* Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase<br>* Other names: Sustiva®;Drug: Lamivudine<br>* Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase<br>* Other names: Epivir®;|
| Experimental: Arm 3: BMS-986001 (400 mg) + Efavirenz + Lamivudine<br> | Drug: BMS-986001<br>* Capsules, Oral, 400 mg, Once daily, At least 48 weeks<br>Drug: Efavirenz<br>* Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase<br>* Other names: Sustiva®;Drug: Lamivudine<br>* Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase<br>* Other names: Epivir®;|
| Experimental: Arm 4: Tenofovir (300 mg) + Efavirenz + Lamivudine<br> | Drug: Efavirenz<br>* Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase<br>* Other names: Sustiva®;Drug: Lamivudine<br>* Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase<br>* Other names: Epivir®;Drug: Tenofovir<br>* Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase<br>* Other names: Viread®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by polymerase chain reaction (PCR) analyses |  | Week 24 | 
| Safety as measured by numbers of subjects with Serious Adverse Events (SAEs) and numbers of subjects with Adverse Events (AEs) leading to discontinuations |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by PCR analyses |  | Weeks 48 and 96 | 
| Safety as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuation |  | Weeks 48 and 96 | 
| Changes from baseline in CD4+ T-cell counts |  | Weeks 24, 48, and 96 | 
| Numbers of subjects with virologic failure who exhibit genotypic substitutions in viral Ribonucleic acid (RNA) |  | Weeks 24, 48, and 96 | 
| Maximum observed concentration (Cmax) of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 | 
| Time of maximum observed concentration (Tmax) of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 | 
| Trough plasma concentration at 24 h post observed dose (Cmin) of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 | 
| Trough plasma concentration pre-dose (C0) of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 | 
| Area under the concentration-time curve in one dosing interval [AUC(0-24)] of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 | 
| Average steady-state plasma concentration (Css,avg) of BMS-986001 when co-administered with EFV and 3TC |  | Week 24 |