HIV-1-infection
Conditions
Brief summary
The goal of this clinical study is to learn about the safety and tolerability of bictegravir (BIC)/lenacapavir (LEN) and to learn how the study drug interacts with the body in virologically suppressed (VS) children and adolescents with human immunodeficiency virus type 1 (HIV-1) on a stable and complex antiretroviral (ARV) regimen. The study will also assess the safe loading dose of LEN and pharmacokinetics (PK) of BIC/LEN. The primary objectives of this study are: * To evaluate the steady-state PK of BIC and LEN and confirm the dose of the LEN loading dose and BIC/LEN FDC in VS children and adolescents with HIV-1. * To evaluate the safety and tolerability of BIC/LEN through Week 24 in VS children and adolescents with HIV-1.
Interventions
DRUGLenacapavir
Tablets administered orally without regard to food
DRUGBictegravir/Lenacapavir (BIC/LEN) FDC
Tablets administered orally without regard to food
DRUGBictegravir/Lenacapavir
Tablets administered orally without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age and body weight at screening: * Cohort 1: ≥ 12 years to \< 18 years weighing ≥ 35 kg. * Cohort 2: ≥ 6 years to \< 12 years weighing ≥ 25 kg to \< 35 kg. * Cohort 3: ≥ 2 years to \< 6 years weighing ≥ 10 kg to \< 25 kg. * On a complex ARV regimen. Complex regimens are any ARV therapy that is not a single-tablet regimen taken once daily (eg, \> 1 tablet or any other formulation a day). * Documented plasma HIV-1 ribonucleic acid (RNA) levels must be \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \< 50 copies/mL) in the last 6 months prior to screening (at least 1 measure prior to screening). * Plasma HIV-1 RNA levels \< 50 copies/mL at screening. * No documented or suspected resistance to integrase strand transfer inhibitors (mutations T66A/I/K, E92G/Q/V, G118R, F121C/Y, G140R, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene). * The following laboratory parameters at screening: * Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula. * Absolute neutrophil count \> 0.50 cells/L (\> 500 cells/mm3). * Hemoglobin ≥ 85 g/L (\> 8.5 g/dL). * Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3). * Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 5 x upper limit of normal. * Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL). Key
Exclusion criteria
* CD4 cell count \< 200 cells/mm\^3. * CD4 percentage \< 20%. * Life expectancy ≤ 1 year. * An opportunistic illness indicative of Stage 3 HIV diagnosed within the 30 days prior to screening. * Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening. * Acute hepatitis within 30 days prior to screening. * Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed). * Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B virus (HBV) core antibody (antibody against hepatitis B core antigen \[anti-HBc\]) at screening. If a participant is negative for HBsAg and positive for anti-HBc but HBV DNA is undetectable, the participant may be enrolled. * A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).Current alcohol or substance use judged by the investigator to potentially interfere with the participant's study compliance. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Cmax of BIC and LEN at Steady State | Day 1 up to Week 24, as appropriate | Cmax is defined as the maximum observed concentration of drug at steady state. |
| PK Parameter: AUCtau of BIC and LEN at Steady State | Day 1 up to Week 24, as appropriate | AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state. |
| PK Parameter: Ctrough of BIC and LEN at Steady State | Day 1 up to Week 24, as appropriate | Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state. |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24 | First dose date up to Week 24 | — |
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24 | First dose date up to Week 24 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: AUClast for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration at steady state. |
| PK Parameter: Tmax for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | Tmax is defined as the time (observed time point) of Cmax at steady state. |
| PK Parameter: Tlast for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | Tlast is defined as the time (observed time point) of Clast at steady state. Clast is defined as the last measurable concentration (above the quantification limit). |
| PK Parameter: T1/2 for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | T1/2 is defined as the terminal elimination half-life at steady state. |
| PK Parameter: CL for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | Clearance (CL) is the volume of plasma cleared of drug over a specified time period, at a steady state. |
| PK Parameter: Vz for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | Volume of distribution (Vz) is defined as the extent to in which the drug is distributed in the body tissue, rather than the plasma, to produce the desired effects at a steady state. |
| PK Parameter: λz for BIC and LEN at Steady State | Day 1 up to Week 48, as appropriate | λz is defined as the terminal elimination rate constant, which determines the rate at which the drug will be eliminated from the body after it is absorbed and distributed at a steady state. |
| Percentage of Participants Experiencing TEAEs Through Week 48 | First dose date up to Week 48 | — |
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48 | First does date up to Week 48 | — |
| Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 24 Based on the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm | Week 24 | — |
| Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 48 Based on the United States FDA-Defined Snapshot Algorithm | Week 48 | — |
| Change from Baseline in Clusters of Differentiation 4 (CD4) Cell Counts at Week 24 | Baseline, Week 24 | — |
| Change from Baseline in CD4 Percentage at Week 24 | Baseline, Week 24 | — |
| Change from Baseline in CD4 Cell Counts at Week 48 | Baseline, Week 48 | — |
| Change from Baseline in CD4 Percentage at Week 48 | Baseline, Week 48 | — |
| Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire | Day 1 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
| Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire | Day 2 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
| Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire | Day 1 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
| Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire | Week 4 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
| Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire | Week 24 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
| Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire | Week 48 | Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Countries
Argentina, Italy, South Africa, Spain, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed