HIV-1-infection
Conditions
Brief summary
The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC) plus lenacapavir (LEN), versus current therapy (Phase 2) and BIC/LEN fixed-dose combination (FDC) versus current therapy (Phase 3) in people living with HIV (PWH).
Interventions
DRUGBictegravir
Tablets administered orally without regard to food
DRUGLenacapavir
Tablets administered orally without regard to food
DRUGBIC/LEN FDC
Tablets administered orally without regard to food
DRUGStable Baseline Regimen
SBR will include a combination of antiretroviral (ARV) regimen. ARV regimen may include the following, except for participants taking a single tablet regimen or taking a complete parenteral regimen (Cabenuva). * Nucleos(t)ide Reverse Transcriptase Inhibitors: * Abacavir * Emtricitabine * Lamivudine * Tenofovir alafenamide * Tenofovir disoproxil fumarate * Zidovudine * Non-Nucleosite Reverse Transcriptase Inhibitors: * Delavirdine * Efavirenz * Nevirapine * Rilpivirine * Doravirine * Integrase Inhibitors: * Bictegravir * Cabotegravir * Dolutegravir * Elvitegravir * Raltegravir * Protease Inhibitors: * Atazanavir * Darunavir * Fosamprenavir * Indinavir * Lopinavir * Nelfinavir * Saquinavir * Tipranavir * Chemokine Co-receptor 5 (CCR5) Antagonist: * Maraviroc * Fusion Inhibitors: * Enfuvirtide * gp120 Attachment Inhibitor: * Fostemsavir * Anti-CD4 Monoclonal Antibodies: * Ibalizumab-uiyk
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * If plasma HIV-1 RNA measurements in the 6 months prior to screening are available, all levels must be \< 50 copies/mL. * At least one documented plasma HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL * Plasma HIV-1 RNA levels \< 50 copies/mL at screening. * Currently receiving a complex antiretroviral (ARV) regimen due to previous viral resistance, or intolerance, or contraindication to existing single-tablet regimens (STR), and on this regimen for at least 6 months prior to the screening visit. The criteria to define a complex regimen in this study are as follows: * A regimen containing a boosted protease inhibitor or a nonnucleos(t)ide reverse transcriptase inhibitor (NRTI) plus at least 1 other third agent (ie, an agent from a class other than NRTIs) (eg, bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)(BVY) + darunavir/cobicistat, BVY + etravirine), or * A regimen of ≥ 2 pills/day, or a regimen requiring dosing more than once daily, or * A regimen containing parenteral agent(s) (excluding a complete long-acting injectable regimen, such as intramuscular cabotegravir plus rilpivirine) as well as oral agents. * No documented or suspected resistance to bictegravir (BIC). * Estimated glomerular filtration rate ≥ 15 mL/min according to the Cockcroft-Gault formula for creatinine clearance (CLcr) who are not on renal replacement therapy. Key
Exclusion criteria
* Prior use of, or exposure to, lenacapavir (LEN) * Active tuberculosis infection * Chronic hepatitis B virus (HBV) infection Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) ≥ 50 Copies/mL at Week 24 as Determined by the United States Food and Drug Administration (US FDA) Defined Snapshot Algorithm | Week 24 | Participants who had the last available on-treatment HIV-1 RNA≥ 50 copies/mL in the week 24 analysis window, or who did not have on-treatment HIV-1 RNA data in the week 24 analysis window and participants who discontinued study drug prior to or in the week 24 analysis window due to lack of efficacy, or who discontinued study drug prior to or in the week 24 analysis window due to adverse event (AE) or death and have the last available on-treatment HIV-1 RNA≥ 50 copies/mL, or who discontinued study drug prior to or in the week 24 analysis window due to reasons other than AE, death, or lack of efficacy and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL were included. The Week 24 window for snapshot algorithm was between Days 127 and 210 (inclusively). Percentages were rounded off. |
| Phase 3: Percentages of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | Participants who had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 analysis window, or who did not have on-treatment HIV-1 RNA data in the Week 48 analysis window and who discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or who discontinued study drug prior to or in the Week 48 analysis window due to AE or death and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or who discontinued study drug prior to or in the Week 48 analysis window due to reasons other than AE, death, or lack of efficacy and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL were included. The Week 48 window for snapshot algorithm was between Days 295 and 378 (inclusively). Percentages were rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | Week 24 | Participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 24 analysis window were included. The Week 24 window for snapshot algorithm was between Days 127 and 210 (inclusively). Percentages were rounded off. |
| Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 24 | Baseline, Week 24 | — |
| Phase 2: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24 | First dose date up to Week 24 | An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment. TEAEs were defined as any AE that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus 60 days (for BIC+LEN or BIC/LEN FDC) or 30 days (for SBR) or any AE leading to study drug discontinuation. Percentages were rounded off. |
| Phase 2: PK Parameter: Cmax for Bictegravir (BIC) at Steady State | At Week 16 or 24 | Cmax is defined as the maximum observed concentration of drug. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 2: PK Parameter: Cmax for Lenacapavir (LEN) at Steady State | At Week 16 or Week 24 | Cmax is defined as the maximum observed concentration of drug. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 2: PK Parameter: AUCtau of BIC at Steady State | At Week 16 or 24 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 2: PK Parameter: AUCtau for LEN at Steady State | At Week 16 or Week 24 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 2: PK Parameter: Ctrough of BIC at Steady State | At Week 16 or Week 24 | Ctrough is defined as the observed drug concentration at the end of the dosing interval. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 2: PK Parameter: Ctrough of LEN at Steady State | At Week 16 or Week 24 | Ctrough is defined as the observed drug concentration at the end of the dosing interval. Participants chose to participate at either Week 16 or Week 24 visit as the steady state visit. |
| Phase 3: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | Participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 48 analysis window were included. The Week 48 window for snapshot algorithm was between Days 295 and 378 (inclusively). |
| Phase 3: Change From Baseline in CD4 Cell Count at Week 48 | Baseline, Week 48 | An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment. TEAEs were defined as any AE that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus 60 days (for BIC+LEN or BIC/LEN FDC) or 30 days (for SBR) or any AE leading to study drug discontinuation. Percentages were rounded off. |
| Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48 | First dose date up to Week 48 | An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment. TEAEs were defined as 1 or both of the following: Any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off. |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm | Week 96 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 144 as Determined by the US FDA-defined Snapshot Algorithm | Week 144 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm | Week 96 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 as Determined by the US FDA-defined Snapshot Algorithm | Week 144 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 96 | Baseline, Week 96 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 144 | Baseline, Week 144 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants Experiencing TEAEs Through Week 96 | Week 96 | — |
| Phase 3 Treatment Group 1: (BIC/LEN 75 mg/50 mg FDC): Percentage of Participants Experiencing TEAEs Through Week 144 | Week 144 | — |
Countries
Argentina, Australia, Canada, Dominican Republic, France, Germany, Italy, Japan, Puerto Rico, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in South America, Oceania, North America, Europe, Asia and Africa.
Pre-assignment details
Overall, 891 participants were screened: 162 in Phase 2 and 729 in Phase 3. Data submitted represents primary analysis performed on data collected by the Primary Completion Date. Complete data will be submitted within 1 year from the Study Completion date.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 211 Participants |
| Age, Categorical Between 18 and 65 years | 474 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 9.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 18 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Collected | 39 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 21 Participants |
| Race/Ethnicity, Customized Other or More Than One Race | 0 Participants |
| Race/Ethnicity, Customized White | 124 Participants |
| Region of Enrollment Argentina | 0 Participants |
| Region of Enrollment Australia | 2 Participants |
| Region of Enrollment Canada | 81 Participants |
| Region of Enrollment Dominican Republic | 0 Participants |
| Region of Enrollment France | 34 Participants |
| Region of Enrollment Germany | 47 Participants |
| Region of Enrollment Italy | 0 Participants |
| Region of Enrollment Japan | 3 Participants |
| Region of Enrollment Puerto Rico | 1 Participants |
| Region of Enrollment South Africa | 6 Participants |
| Region of Enrollment South Korea | 0 Participants |
| Region of Enrollment Spain | 39 Participants |
| Region of Enrollment Taiwan | 0 Participants |
| Region of Enrollment United Kingdom | 0 Participants |
| Region of Enrollment United States | 134 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 1 / 52 | 0 / 25 | 5 / 373 | 0 / 188 |
| other Total, other adverse events | 20 / 51 | 13 / 52 | 5 / 25 | 141 / 371 | 70 / 186 |
| serious Total, serious adverse events | 3 / 51 | 2 / 52 | 2 / 25 | 52 / 371 | 22 / 186 |
Outcome results
None listed