Phase 3
N=55
Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
HIV · HIV Infections · Acquired Immunodeficiency Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT01967940 ↗Enrolled (actual)
55
Serious AEs
7.6%
Results posted
Jun 2017
Primary outcome: Primary: Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 — 58.3; 60.7; 0 percentage of participants — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- TAF (Drug); Placebo (Drug); E/C/F/TAF (Drug); Current failing ARV regimen (Drug); ATV (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- May 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 |
58.3; 60.7; 0 | <0.001 sig |
| SECONDARY Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10 |
-0.72; -0.70; -0.04 | — |
| SECONDARY Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24 |
37.8 | — |
| SECONDARY Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48 |
48.6 | — |
| SECONDARY Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24 |
75.7 | — |
| SECONDARY Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48 |
81.1 | — |
| SECONDARY Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 |
86.5 | — |
| SECONDARY Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 |
97.3 | — |
| SECONDARY Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 |
94.6 | — |
| SECONDARY Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48 |
97.3 | — |
| SECONDARY Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24 |
-2.96 | — |
| SECONDARY Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48 |
-3.04 | — |
| SECONDARY Part 2: Change From Baseline in CD4+ Cell Count at Week 24 |
76 | — |
| SECONDARY Part 2: Change From Baseline in CD4+ Cell Count at Week 48 |
125 | — |
| SECONDARY Part 2: Change From Baseline in CD4+ Percentage at Week 24 |
4.4 | — |
| SECONDARY Part 2: Change From Baseline in CD4+ Percentage at Week 48 |
5.7 | — |
Summary
The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2.
Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen.
In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a > 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.
Eligibility Criteria
Key Inclusion Criteria
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- Currently taking a failing ARV regimen
- Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
- Normal ECG
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
- Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Adequate hematologic function
- Serum amylase ≤ 5 × ULN
- Females may enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation [for ≥ 12 months] of previously occurring menses), or
- Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following study drug dosing
- Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
- Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
- Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
Key Exclusion Criteria
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Hepatitis B surface antigen (HBsAg) positive
- Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll)
- History of integrase inhibitor use
- Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.
- Screening or historical genotype report shows resistance to integrase inhibitors
- Individuals experiencing decompensated cirrhosis
- Current alcohol or substance use
- History of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Part 1, Day 1 and must not be anticipated to require systemic therapy during the study.
- Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Part 1, Day 1
- Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements
- Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
- Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT01967940). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.