Undersøgelse af Bictegravir/Lenacapavir hos børn og unge med HIV-1
En fase 2/3, åben-label undersøgelse til evaluering af farmakokinetik, sikkerhed og antiviral aktivitet af Bictegravir/Lenacapavir hos børn og unge med HIV-1
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 3
Kontakter og lokationer
Studiesteder
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Buenos Aires, Argentina, C1141ACG,
- Helios Salud S.A
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20010
- Children's National Hospital
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Florida
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Tampa, Florida, Forenede Stater, 33612
- University of South Florida
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Georgia
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Atlanta, Georgia, Forenede Stater, 30308
- Grady Ponce de Leon Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60614
- Ann and Robert H. Lurie Children's Hospital of Chicago
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Milan, Italien, 20157
- ASST FBF Sacco Ospedale Sacco
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Roma, Italien, 00165
- IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
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Madrid, Spanien, 28046
- Hospital Universitario La Paz
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Madrid, Spanien, 28007
- Hospital General Universitario Gregorio Marano
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Madrid, Spanien, 28041
- Hospital Universitario 12 De Octubre
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Cape Town, Sydafrika, 7505
- FAMCRU Ukwanda School for Rural Health
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Cape Town, Sydafrika, 7646
- Be Part Yoluntu
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Durban, Sydafrika, 3629
- Durban International Clinical Research Site, Enhancing Care Foundation
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East London, Sydafrika, 5219
- Monti Clinical Research Centre
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Johannesburg, Sydafrika, 1862
- Perinatal HIV Research Unit
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Johannesburg, Sydafrika, 2038
- Wits RHI Shandukani Research Centre CRS
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Johannesburg, Sydafrika, 2112
- Nkanyezi VIDA Research Unit
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Ka-Majosi, Sydafrika, 944
- Khomanani Health Research and Wellness Centre
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KwaDukuza, Sydafrika, 4449
- Clinical Research Institute of South Africa (CRISA)
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Pretoria, Sydafrika, 0087
- The Aurum Institute: Pretoria Clinical Research Centre
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Soshanguve, Sydafrika, 0152
- Setshaba Research Centre
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Key Inclusion Criteria:
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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.
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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).
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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).
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Plasma HIV-1 RNA levels < 50 copies/mL at screening.
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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).
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The following laboratory parameters at screening:
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Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula.
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Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3).
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Hemoglobin ≥ 85 g/L (> 8.5 g/dL).
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Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3).
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Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase)
≤ 5 x upper limit of normal.
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Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL).
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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/Exclusion criteria may apply.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN TOS 75/50 mg FDC
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN TOS 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Andre navne:
Tablets administered orally without regard to food
Andre navne:
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Eksperimentel: Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Andre navne:
Tablets administered orally without regard to food |
|
Eksperimentel: Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Andre navne:
Tablets administered orally without regard to food |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Procentdel af deltagere, der oplever behandlingsfremkaldte bivirkninger (TEAE) til og med uge 24
Tidsramme: Første dosisdato op til uge 24
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Første dosisdato op til uge 24
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Procentdel af deltagere, der oplever behandlings-opståede laboratorieabnormaliteter gennem uge 24
Tidsramme: Første dosisdato op til uge 24
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Første dosisdato op til uge 24
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PK Parameter: Cmax of BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 24, as appropriate
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Cmax is defined as the maximum observed concentration of drug at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: AUCtau of BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 24, as appropriate
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AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: Ctrough of BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 24, as appropriate
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Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Procentdel af deltagere, der oplever TEAEs gennem uge 48
Tidsramme: Første dosisdato op til uge 48
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Første dosisdato op til uge 48
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Procentdel af deltagere, der oplever behandlings-opståede laboratorieabnormaliteter gennem uge 48
Tidsramme: Den første daterer op til uge 48
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Den første daterer op til uge 48
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Andel af deltagere med plasma HIV-1 RNA < 50 kopier/ml og ≥ 50 kopier/ml i uge 24 Baseret på USA (USA) Food and Drug Administration (FDA)-defineret snapshot-algoritme
Tidsramme: Uge 24
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Uge 24
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Andel af deltagere med plasma HIV-1 RNA < 50 kopier/ml og ≥ 50 kopier/ml i uge 48 Baseret på den amerikanske FDA-definerede snapshotalgoritme
Tidsramme: Uge 48
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Uge 48
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Ændring fra baseline i Clusters of Differentiation 4 (CD4) celletællinger i uge 24
Tidsramme: Baseline, uge 24
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Baseline, uge 24
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Ændring fra baseline i CD4-procent i uge 24
Tidsramme: Baseline, uge 24
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Baseline, uge 24
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Ændring fra baseline i CD4-celleantal i uge 48
Tidsramme: Baseline, uge 48
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Baseline, uge 48
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Ændring fra baseline i CD4-procent i uge 48
Tidsramme: Baseline, uge 48
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Baseline, uge 48
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PK Parameter: AUClast for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tmax for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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Tmax is defined as the time (observed time point) of Cmax at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tlast for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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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). |
Day 1 up to Week 48, as appropriate
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PK Parameter: T1/2 for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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T1/2 is defined as the terminal elimination half-life at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: CL for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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Clearance (CL) is the volume of plasma cleared of drug over a specified time period, at a steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Vz for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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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. |
Day 1 up to Week 48, as appropriate
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PK Parameter: λz for BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 48, as appropriate
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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. |
Day 1 up to Week 48, as appropriate
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire
Tidsramme: Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire
Tidsramme: Day 2
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 2
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Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire
Tidsramme: Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire
Tidsramme: Week 4
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 4
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire
Tidsramme: Week 24
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 24
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire
Tidsramme: Week 48
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 48
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Gilead Study Director, Gilead Sciences
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- GS-US-621-6463
- 2023-509428-16 (Anden identifikator: European Medicines Agency)
- 2023 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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