Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

15 Oct 2024 → ongoing

Decision date (initial)

2024-09-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

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

Secondary objectives 4

1. To evaluate additional steady-state PK parameters of BIC and LEN in VS children and adolescents with HIV-1
2. To evaluate the safety and tolerability of BIC/LEN through Week 48 in VS children and adolescents with HIV-1
3. To evaluate the antiviral activity of BIC/LEN at Weeks 24 and 48 in VS children and adolescents with HIV-1
4. To evaluate the acceptability and palatability of the LEN and BIC/LEN FDC oral formulations in VS children and adolescents with HIV-1

Conditions and MedDRA coding

HIV-1 Infection

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-284569-PIP20-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participants must meet all of the following inclusion criteria to be eligible for participation in this study: Parent, guardian, or legally authorized representative willing and able to provide written informed consent prior to performing study procedures as required by local country regulations.
2. Participant willing and able to provide written assent if possible (in accordance with their local institutional guidelines and local country regulations).
3. 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
4. On a complex ARV regimen. Complex regimens are any ART that is not a STR taken once daily (eg, > 1 tablet or any other formulation a day).
5. Documented plasma HIV-1 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).
6. Plasma HIV-1 RNA levels < 50 copies/mL at screening.
7. No documented or suspected resistance to INSTIs (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).
8. The following laboratory parameters at screening: a) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 using Bedside Schwartz formula. b) Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3). c) Hemoglobin ≥ 85 g/L (> 8.5 g/dL). d) Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3). e) Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 5 x upper limit of normal. f) Total bilirubin ≤ 23 µmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 µmol/L (≤ 0.4 mg/dL).
9. Negative serum beta-human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test at Day 1 for participants assigned female at birth of childbearing potential only (as defined in Appendix 11.5).
10. Lactating people must agree to discontinue nursing before administration of the study drugs.

Exclusion criteria 14

1. Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study: CD4 cell count < 200 cells/mm3.
2. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.
3. Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor throughout the study.
4. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
5. Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.3.1.
6. CD4 percentage < 20%.
7. Life expectancy ≤ 1 year.
8. An opportunistic illness indicative of Stage 3 HIV diagnosed within 30 days prior to screening (as defined in Appendix 11.9).
9. Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening.
10. Acute hepatitis within 30 days prior to screening.
11. Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).
12. 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.
13. A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
14. Current alcohol or substance use judged by the investigator to potentially interfere with the participant’s study compliance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Steady-state PK parameters (Cmax, AUCtau, and Ctau) of BIC and LEN
2. Proportion of participants experiencing treatment-emergent AEs through Week 24
3. Proportion of participants experiencing treatment-emergent laboratory abnormalities through Week 24

Secondary endpoints 7

1. Steady-state PK parameters (AUClast, Ctrough, Tmax, Tlast, t1/2, CL, Vz, and λz) for BIC and LEN
2. Proportion of participants experiencing treatment-emergent AEs through Week 48
3. Proportion of participants experiencing treatment-emergent laboratory abnormalities through Week 48
4. Proportion of participants with plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Weeks 24 and 48 based on the US Food and Drug Administration (FDA)-defined snapshot algorithm
5. Change from baseline in CD4 cell counts and percentages at Weeks 24 and 48
6. Acceptability and palatability summary of LEN oral loading dose at Day 1 and Day 2 assessed by questionnaire
7. Acceptability and palatability summary of oral BIC/LEN oral FDC at Day 1, Week 4, Week 24, and Week 48 assessed by questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 7

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications