A Phase 3b, Randomized, Open-label Clinical Study to Demonstrate Non-inferiority in Virologic Response Rates of HIV-1 RNA Suppression <400 Copies/mL of TDF/FTC/RPV Versus TDF/FTC/EFV in First-line Antiretroviral NNRTI-based Suppressed Patients. Switching At Low HIV-1 RNA Into Fixed Dose Combinations (SALIF)
Overview
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 426
- Primary Endpoint
- Percentage of Participants With Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 400 Copies Per Milliliter (Copies/mL) at Week 48
Overview
Brief Summary
The purpose of this study is to demonstrate noninferiority (a new treatment is equivalent to standard treatment) in terms of the percentage of patients who have plasma human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) levels less than 400 copies per mL after 48 weeks of randomized treatment with tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) versus TDF/FTC/efavirenz (TDF/FTC/EFV).
Detailed Description
This is a 48-week, multicenter (study conducted at multiple sites), multinational (conducted at different countries), open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance) study to assess whether tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) shows noninferior response rates of human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) suppression less than 400 copies per mL, compared with TDF/FTC/efavirenz (TDF/FTC/EFV). The study consists of 3 phases including, the screening phase (of 6 weeks), treatment phase (of 48 weeks), and follow up phase (of 30 to 35 days after the last dose of study medication). During the 48 weeks treatment phase, patients currently with HIV-1 RNA suppression less than 50 copies per mL on their first-line antiretroviral regimen, will be randomized in a 1:1 ratio, in 2 groups, ie, Group 1 (treatment group) and Group 2 (control group). Both these groups will receive a fixed dose combination (FDC) regimen (ie, FDC tablet: one tablet per day) of either TDF/FTC/RPV in Group 1 or TDF/FTC/EFV in Group 2. Patients will return for study visits at Week 4, 12, 24, 36, and 48 during the treatment period, and then every 24 weeks thereafter during the extended treatment period until the last patient has his or her Week 48 (or treatment discontinuation) visit. Safety evaluations for adverse events, clinical laboratory (central and local) tests, electrocardiogram, vital signs, and physical examination will be performed throughout the study. The treatment duration for each patient will be expected to be between 48 and 108 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Documented human immunodeficiency virus-type 1 (HIV-1) infection Patients who have been receiving first line highly active antiretroviral therapy (HAART) for at least 1 year before the screening visit Patients who have been taking the same ARV combination for at least 8 weeks before the screening visit and are expected to continue on this regimen throughout the screening period.
- •Patients who prefer to change the current HAART regimen for reasons of simplification and/or toxicity of nucleoside/nucleotide reverse transcriptase inhibitor (N\[t\]RTI) Plasma HIV-1 RNA less than 50 copies per mL and CD4+ cell count higher than 200 per mm3 at the screening visit Agrees to protocol-defined use of effective contraception
Exclusion Criteria
- •History of virologic failure (2 consecutive plasma HIV-1 ribonucleic acid (RNA) more than or equal to 400 copies per mL) while on previous or current ART History of immunologic failure (2 consecutive CD4+ cell counts during HAART treatment falling below the pre-HAART level) History of any primary N\[t\]RTI or NNRTI mutations Has a previously documented HIV-2 infection Significantly decreased hepatic function or hepatic insufficiency or diagnosed with acute clinical viral hepatitis Diagnosed with Mycobacterium tuberculosis infection Severe laboratory abnormalities Creatinine clearance less than 50 mL per minute Addicted to drug, including alcohol or recreational drugs
Arms & Interventions
Group 1
Patients will receive fixed dose combination (FDC) tablet of tenofovir disoproxil fumarate/emtricitabine/rilpivirine with a meal, until Week 48.
Intervention: Rilpivirine (Drug)
Group 1
Patients will receive fixed dose combination (FDC) tablet of tenofovir disoproxil fumarate/emtricitabine/rilpivirine with a meal, until Week 48.
Intervention: Tenofovir disoproxil fumarate (Drug)
Group 1
Patients will receive fixed dose combination (FDC) tablet of tenofovir disoproxil fumarate/emtricitabine/rilpivirine with a meal, until Week 48.
Intervention: Emtricitabine (Drug)
Group 2
Patients will receive FDC tablet of tenofovir disoproxil fumarate/emtricitabine /efavirenz on an empty stomach at bedtime, until Week 48.
Intervention: Efavirenz (Drug)
Group 2
Patients will receive FDC tablet of tenofovir disoproxil fumarate/emtricitabine /efavirenz on an empty stomach at bedtime, until Week 48.
Intervention: Tenofovir disoproxil fumarate (Drug)
Group 2
Patients will receive FDC tablet of tenofovir disoproxil fumarate/emtricitabine /efavirenz on an empty stomach at bedtime, until Week 48.
Intervention: Emtricitabine (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 400 Copies Per Milliliter (Copies/mL) at Week 48
Time Frame: Week 48
Percentage of Participants with viral load (plasma HIV-1 RNA levels) less than 400 copies per mL at Week 48, obtained by the modified Food and Drug Administration (FDA) Snapshot method.
Secondary Outcomes
- Percentage of Participants With Plasma HIV-1 RNA Levels More Than or Equal to (>=) 400 Copies/mL at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.(Week 48)
- Percentage of Participants With Plasma HIV-1 RNA Levels < 50 Copies/mL at Week 48(Week 48)
- Percentage of Participants With Plasma HIV-1 RNA Levels >= 50 Copies Per Milliliter (Copies/mL) at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.(Week 48)
- Percentage of Participant With Treatment Adherence Based on Tablet Count(Up to 48 Weeks)
- Number of Participants With Treatment-Emergent Nucleoside Reverse Transcriptase Inhibitor (N[t]RTI) or Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NNRTI) Mutations(Up to Week 48)