Studie av Bictegravir/Lenacapavir hos barn og ungdom med HIV-1
En fase 2/3, åpen studie for å evaluere farmakokinetikken, sikkerheten og den antivirale aktiviteten til Bictegravir/Lenacapavir hos barn og ungdom 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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 3
Kontakter og plasseringer
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, Forente stater, 20010
- Children's National Hospital
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Florida
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Tampa, Florida, Forente stater, 33612
- University of South Florida
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Georgia
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Atlanta, Georgia, Forente stater, 30308
- Grady Ponce de Leon Center
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Illinois
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Chicago, Illinois, Forente stater, 60614
- Ann and Robert H. Lurie Children's Hospital of Chicago
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Milan, Italia, 20157
- ASST FBF Sacco Ospedale Sacco
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Roma, Italia, 00165
- IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
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Madrid, Spania, 28046
- Hospital Universitario La Paz
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Madrid, Spania, 28007
- Hospital General Universitario Gregorio Marano
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Madrid, Spania, 28041
- Hospital Universitario 12 De Octubre
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Cape Town, Sør-Afrika, 7505
- FAMCRU Ukwanda School for Rural Health
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Cape Town, Sør-Afrika, 7646
- Be Part Yoluntu
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Durban, Sør-Afrika, 3629
- Durban International Clinical Research Site, Enhancing Care Foundation
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East London, Sør-Afrika, 5219
- Monti Clinical Research Centre
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Johannesburg, Sør-Afrika, 1862
- Perinatal HIV Research Unit
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Johannesburg, Sør-Afrika, 2038
- Wits RHI Shandukani Research Centre CRS
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Johannesburg, Sør-Afrika, 2112
- Nkanyezi VIDA Research Unit
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Ka-Majosi, Sør-Afrika, 944
- Khomanani Health Research and Wellness Centre
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KwaDukuza, Sør-Afrika, 4449
- Clinical Research Institute of South Africa (CRISA)
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Pretoria, Sør-Afrika, 0087
- The Aurum Institute: Pretoria Clinical Research Centre
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Soshanguve, Sør-Afrika, 0152
- Setshaba Research Centre
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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 navn:
Tablets administered orally without regard to food
Andre navn:
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Eksperimentell: 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 navn:
Tablets administered orally without regard to food |
|
Eksperimentell: 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 navn:
Tablets administered orally without regard to food |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Prosentandel av deltakere som opplever behandlingsoppståtte bivirkninger (TEAE) gjennom uke 24
Tidsramme: Første dosedato frem til uke 24
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Første dosedato frem til uke 24
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Prosentandel av deltakere som opplever behandlingsoppståtte laboratorieavvik gjennom uke 24
Tidsramme: Første dosedato frem til uke 24
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Første dosedato frem til uke 24
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|
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PK Parameter: Cmax of BIC and LEN at Steady State
Tidsramme: Day 1 up to Week 24, as appropriate
|
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
|
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
|
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 |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Prosentandel av deltakere som opplever TEAEs gjennom uke 48
Tidsramme: Første dosedato frem til uke 48
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Første dosedato frem til uke 48
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Prosentandel av deltakere som opplever behandlingsoppståtte laboratorieavvik gjennom uke 48
Tidsramme: Den første dateres til uke 48
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Den første dateres til uke 48
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Andel deltakere med plasma HIV-1 RNA < 50 kopier/ml og ≥ 50 kopier/ml ved uke 24 Basert på USAs (USA) Food and Drug Administration (FDA)-definert øyeblikksbildealgoritme
Tidsramme: Uke 24
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Uke 24
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Andel deltakere med plasma HIV-1 RNA < 50 kopier/ml og ≥ 50 kopier/ml ved uke 48 Basert på USAs FDA-definerte øyeblikksbildealgoritme
Tidsramme: Uke 48
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Uke 48
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Endring fra baseline i grupper av differensiering 4 (CD4) celletall i uke 24
Tidsramme: Baseline, uke 24
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Baseline, uke 24
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Endring fra baseline i CD4-prosent ved uke 24
Tidsramme: Baseline, uke 24
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Baseline, uke 24
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Endring fra baseline i CD4-celletall i uke 48
Tidsramme: Grunnlinje, uke 48
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Grunnlinje, uke 48
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Endring fra baseline i CD4-prosent ved uke 48
Tidsramme: Grunnlinje, uke 48
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Grunnlinje, uke 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
|
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
|
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
|
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
|
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
|
Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 48
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Gilead Study Director, Gilead Sciences
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Mer informasjon
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Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- GS-US-621-6463
- 2023-509428-16 (Annen identifikator: European Medicines Agency)
- 2023 (U.S. NIH-stipend/kontrakt)
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