Clinical trial NCT04375800: Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Ages 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Human Immunodeficiency Virus (HIV) Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-05-05
Enrollment: 84
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 first primary objective is 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. The second primary objective is 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 in which they may continue to receive DOR until it is commercially available, or for up to an additional 224 weeks (whichever comes first).

Eligibility criteria: Inclusion Criteria:

* Has HIV-1 infection confirmed at screening
* Has treatment history defined as either TN or with documented viral suppression (HIV-1 RNA \<50 copies/mL) for ≥3 months on combination antiretroviral therapy (cART)
* 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 DOR plus the 2 NRTIs selected by the investigator, or 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 plus 2 NRTIs selected by the investigator.
* 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 plus 2 NRTIs selected by the investigator until DOR is available commercially 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

Primary outcomes:
measure: Area under the concentration-time curve from 0 to 24 hours postdose (AUC0-24hr) of DOR with 2 NRTIs in plasma at steady-state
timeFrame: Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
measure: Maximum concentration (Cmax) of DOR with 2 NRTIs in plasma at steady-state
timeFrame: Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
measure: Concentration at 24 hours (C24) of DOR with 2 NRTIs in plasma at steady-state
timeFrame: 24 hours postdose on Day 42
measure: Time to maximum concentration (Tmax) of DOR with 2 NRTIs in plasma at steady-state
timeFrame: Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
measure: Percentage of participants with ≥1 adverse event (AE)
timeFrame: Up to 24 weeks
measure: Percentage of participants with a Grade 3 or 4 AE
timeFrame: Up to 24 weeks
measure: Percentage of participants with overall mortality
timeFrame: Up to 24 weeks
measure: Percentage of participants discontinuing from study treatment due to an AE
timeFrame: Up to 24 weeks
measure: Percentage of participants discontinuing from study treatment due to a drug-related AE
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Plasma concentration of DOR
timeFrame: Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
measure: Plasma concentration of 3TC
timeFrame: Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
measure: Plasma concentration of TFV
timeFrame: Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
measure: AUC0-24hr of 3TC
timeFrame: Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
measure: AUC0-24hr of TFV
timeFrame: Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
measure: Cmax of 3TC
timeFrame: Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
measure: Cmax of TFV
timeFrame: Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
measure: Percentage of participants with ≥1 AE
timeFrame: Up to 48 weeks
measure: Percentage of participants with ≥1 AE
timeFrame: Up to 96 weeks
measure: Percentage of participants with Grade 3 or 4 AE
timeFrame: Up to 48 weeks
measure: Percentage of participants with Grade 3 or 4 AE
timeFrame: Up to 96 weeks
measure: Percentage of participants with overall mortality
timeFrame: Up to 48 weeks
measure: Percentage of participants with overall mortality
timeFrame: Up to 96 weeks
measure: Percentage of participants discontinuing from study treatment due to AE
timeFrame: Up to 48 weeks
measure: Percentage of participants discontinuing from study treatment due to AE
timeFrame: Up to 96 weeks
measure: Percentage of participants discontinuing from study treatment due to drug-related AE
timeFrame: Up to 48 weeks
measure: Percentage of participants discontinuing from study treatment due to drug-related AE
timeFrame: Up to 96 weeks
measure: Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL
timeFrame: Up to 24 weeks
measure: Percentage of participants with HIV-1 RNA <50 copies/mL
timeFrame: Up to 48 weeks
measure: Percentage of participants with HIV-1 RNA <50 copies/mL
timeFrame: Up to 96 weeks
measure: Percentage of participants with HIV-1 RNA <200 copies/mL
timeFrame: Up to 24 weeks
measure: Percentage of participants with HIV-1 RNA <200 copies/mL
timeFrame: Up to 48 weeks
measure: Percentage of participants with HIV-1 RNA <200 copies/mL
timeFrame: Up to 96 weeks
measure: Percentage of virologically-suppressed (VS) participants with HIV-1 RNA ≥50 copies/mL
timeFrame: Up to 24 weeks
measure: Percentage of VS participants with HIV-1 RNA ≥50 copies/mL
timeFrame: Up to 48 weeks
measure: Percentage of VS participants with HIV-1 RNA ≥50 copies/mL
timeFrame: Up to 96 weeks
measure: Percentage of treatment-naive (TN) participants with log10 change from baseline in HIV-1 RNA
timeFrame: Day 1 and Week 24
measure: Percentage of TN participants with log10 change from baseline in HIV-1 RNA
timeFrame: Day 1 and Week 48
measure: Percentage of TN participants with log10 change from baseline in HIV-1 RNA
timeFrame: Day 1 and Week 96
measure: Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts
timeFrame: Day 1 and Week 24
measure: Change from baseline in CD4+ T-cell counts
timeFrame: Day 1 and Week 48
measure: Change from baseline in CD4+ T-cell counts
timeFrame: Day 1 and Week 96
measure: Viral resistance-associated substitutions (RASs) to DOR or other treatment components
timeFrame: Up to 96 weeks
measure: Percentage of participants adhering to DOR treatment regimen
timeFrame: Up to 96 weeks
measure: Assessment of palatability/acceptability of DOR pellets/granules
timeFrame: Day 28
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado at Denver ( Site 0108)
state: Colorado
city: Atlanta
country: United States
facility: Emory Children's Center ( Site 0103)
state: Georgia
city: Rionegro.
country: Colombia
facility: Clinica Somer ( Site 1003)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Ciensalud Ips S A S ( Site 1001)
state: Atlantico
city: Cali
country: Colombia
facility: CEIP - Centro de Estudios en Infectología Pediátrica ( Site 1002)
state: Valle Del Cauca
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 0702)
state: Distrito Federal
city: Merida
country: Mexico
facility: Unidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700)
state: Yucatan
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 0701)
city: Kemerovo
country: Russian Federation
facility: Kuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506)
state: Kemerovskaya Oblast
city: Krasnodar
country: Russian Federation
facility: Clinical Centre for Prevention and Control of AIDS ( Site 0504)
state: Krasnodarskiy Kray
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 0507)
state: Krasnoyarskiy Kray
city: Moscow
country: Russian Federation
facility: Infectious Clinical Hospital #2 ( Site 0501)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 0500)
state: Sankt-Peterburg
city: Bloemfontein
country: South Africa
facility: FARMOVS PTY LTD ( Site 0601)
state: Free State
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit ( Site 0602)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute (WRHI) ( Site 0603)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Empilweni Services and Research Unit ( Site 0604)
state: Gauteng
city: Durban
country: South Africa
facility: King Edward Hospital ( Site 0600)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Family Clinic Research With UBUNTU ( Site 0605)
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre ( Site 0606)
state: Western Cape
city: Plettenberg Bay
country: South Africa
facility: Tsitsikamma Clinical Research Initiative (TCRI) ( Site 0607)
state: Western Cape
city: Bangkok
country: Thailand
facility: Siriraj Hospital ( Site 0901)
state: Krung Thep Maha Nakhon
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences ( Site 0902)
city: Khon Kaen
country: Thailand
facility: Faculty of Medicine - Khon Kaen University ( Site 0903)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: