Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066)

Official title

A Phase 2 Clinical Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Participants With HIV-1, Who Are 4 Weeks to Less Than 12 Years of Age and Weigh Less Than 45 kg

Overview

This is a single-group, open-label, multi-site study in pediatric participants with human immunodeficiency virus type 1 (HIV-1) infection, aged 4 weeks to \<12 years and weighing \<45 kg, who are treatment-naive (TN) or have been virologically suppressed (VS) on stable combination antiretroviral therapy (cART) for ≥3 months with no history of treatment failure. The primary objectives are: * To evaluate the steady state pharmacokinetics (PK) of doravirine (DOR) \[MK-1439\] when given in combination with 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) or as part of the fixed-dose combination (FDC) of DOR/lamivudine (3TC)/tenofovir disproxil fumarate (TDF) in participants ≥6 to \<12 years and weighing ≥14 to \<45 kg. * To evaluate the safety and tolerability of DOR when given with 2 NRTIs or as part of the FDC of DOR/3TC/TDF, in participants ≥6 to 12 years and weighing ≥14 to \<45 kg, through Week 24.

Detailed description

Participants who complete the Week 96 visit will be eligible to enroll in an Extension Study and receive DOR until it is commercially available, or for up to an additional 224 weeks (whichever comes first).

Interventions

• Drug Doravirine
  Administered orally
• Drug 2 NRTIs
  Administered orally
• Drug DOR/3TC/TDF
  Administered orally

Primary outcome measures

• Area Under the Concentration-Time Curve (AUC) From 0 to 24 Hours Postdose (AUC0-24hr) of Doravirine (DOR) Following Once-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Maximum Concentration (Cmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Concentration at 24 Hours (C24) of DOR Following Once-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Time to Maximum Concentration (Tmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• AUC From 0 to 12 Hours Postdose (AUC0-12hr) of DOR Following Twice-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose]
• Cmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose]
• Concentration at 12 Hours (C12) of DOR Following Twice-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose]
• Tmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose]
• Percentage of Participants With ≥1 Adverse Event (AE) [Time frame: Up to 24 weeks]
• Percentage of Participants With a Grade 3 or 4 AE [Time frame: Up to 24 weeks]

Secondary outcome measures (12)

• Plasma Concentration of DOR [Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks]
• Plasma Concentration of Lamivudine (3TC) Following Once-Daily Dosing of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) as an Age-Appropriate Fixed-Dose Combination (FDC) [Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks]
• Plasma Concentration of Tenofovir (TFV) Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC [Time frame: Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks]
• AUC0-24hr of 3TC Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• AUC0-24hr of TFV Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Cmax of 3TC Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Cmax of TFV Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC [Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose]
• Percentage of Participants With ≥1 AE at Week 48 [Time frame: Up to 48 weeks]
• Percentage of Participants With ≥1 AE at Week 96 [Time frame: Up to 96 weeks]
• Percentage of Participants With Grade 3 or 4 AE at Week 48 [Time frame: Up to 48 weeks]
• Percentage of Participants With Grade 3 or 4 AE at Week 96 [Time frame: Up to 96 weeks]
• Percentage of Participants With Events of Death at Week 48 [Time frame: Up to 48 weeks]

Eligibility criteria

Inclusion criteria

• Has human immunodeficiency virus type 1 (HIV-1) infection confirmed at screening
• Has appropriate treatment history defined as treatment-naïve (TN) or with documented virologic suppression (HIV-1 ribonucleic acid \[RNA\] <50 copies/mL) on stable combination antiretroviral therapy (cART) for ≥3 months
• Body weight is >3 kg to <45 kg
• If female, is not pregnant or breastfeeding, and one of the following applies:
• Is not a woman of childbearing potential (WOCBP)
• Is a WOCBP using an acceptable form of contraception, or is abstinent
• If a WOCBP must have a negative pregnancy test (urine or serum) within 24 hours of the first dose of study intervention

Study Extension Inclusion Criteria:

• Has completed the Week 96 visit
• Is considered, in the opinion of the investigator, to have derived benefit from treatment with doravirine (DOR) plus the 2 nucleoside/nucleotide analog reverse transcriptase inhibitor (NRTIs) selected by the investigator, or doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), by Week 96 of the study
• Is considered, in the opinion of the investigator, to be a clinically appropriate candidate for additional treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF)
• Understands the procedures in the study extension and has provided (or have the participant's legally acceptable representative, if applicable, provide) documented informed consent/assent to enter the study extension and continue treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF) until it is available locally in countries participating in the study or for up to an additional 224 weeks (whichever comes first)

Exclusion criteria

• Has evidence of renal disease
• Demonstrates evidence of liver disease
• Has clinical or laboratory evidence of pancreatitis
• Has any history of malignancy
• Has presence of any active acquired immunodeficiency syndrome (AIDS)-defining opportunistic Infection
• Has an active diagnosis of hepatitis, including hepatitis B co-infection
• Has current active tuberculosis and/or is being treated with a rifampicin-containing regimen
• Has a medical condition that precludes absorption or intake of oral pellets/granules
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study or interfere with participating for the entire duration of the study
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or other prohibited therapy
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from 45 days prior to Day 1 through the treatment period
• Has a documented or known virologic resistance to DOR
• Has any history of viremia (HIV RNA >1000 copies/mL) after at least 3 months on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Africa · 8 centers

• FARMOVS PTY LTD ( Site 0601) — Bloemfontein
• Perinatal HIV Research Unit ( Site 0602) — Johannesburg
• Wits Reproductive Health and HIV Institute (WRHI) ( Site 0603) — Johannesburg
• Empilweni Services and Research Unit ( Site 0604) — Johannesburg
• King Edward Hospital ( Site 0600) — Durban
• Family Clinic Research With UBUNTU ( Site 0605) — Cape Town
• Be Part Yoluntu Centre ( Site 0606) — Paarl
• Tsitsikamma Clinical Research Initiative (TCRI) ( Site 0607) — Plettenberg Bay

Russia · 5 centers

• Kuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506) — Kemerovo
• Clinical Centre for Prevention and Control of AIDS ( Site 0504) — Krasnodar
• Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 0507) — Krasnoyarsk
• Infectious Clinical Hospital #2 ( Site 0501) — Moscow
• FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 0500) — Saint Petersburg

Colombia · 3 centers

• Clinica Somer ( Site 1003) — Rionegro
• Ciensalud Ips S A S ( Site 1001) — Barranquilla
• CEIP - Centro de Estudios en Infectología Pediátrica ( Site 1002) — Cali

Mexico · 3 centers

• Instituto Nacional de Pediatria ( Site 0701) — Coyoacán
• Hospital Infantil de Mexico Federico Gomez ( Site 0702) — Mexico City
• Unidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700) — Mérida

Thailand · 3 centers

• Siriraj Hospital ( Site 0901) — Bangkok
• Research Institute for Health Sciences ( Site 0902) — Chiang Mai
• Faculty of Medicine - Khon Kaen University ( Site 0903) — Khon Kaen

United States · 2 centers

• University of Colorado at Denver ( Site 0108) — Aurora
• Emory Children's Center ( Site 0103) — Atlanta

Identifiers

NCT: NCT04375800 · 1439-066 · MK-1439-066 · 2019-003955-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗