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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04375800
Other study ID # 1439-066
Secondary ID MK-1439-0662019-
Status Recruiting
Phase Phase 2
First received
Last updated
Start date February 3, 2021
Est. completion date April 11, 2034

Study information

Verified date May 2024
Source Merck Sharp & Dohme LLC
Contact Toll Free Number
Phone 1-888-577-8839
Email Trialsites@merck.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 84
Est. completion date April 11, 2034
Est. primary completion date March 4, 2028
Accepts healthy volunteers No
Gender All
Age group 4 Weeks to 11 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Doravirine
DOR capsules (3.2 to 100 mg); sachets (3.2 to 100 mg); or tablets (100 mg) taken once or twice daily by mouth.
2 NRTIs
Participants receive 2 NRTIs per local label by mouth for 96 weeks as background therapy.

Locations

Country Name City State
Mexico Unidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700) Merida Yucatan
Mexico Hospital Infantil de Mexico Federico Gomez ( Site 0702) Mexico City Distrito Federal
Mexico Instituto Nacional de Pediatria ( Site 0701) Mexico City
Russian Federation Kuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506) Kemerovo Kemerovskaya Oblast
Russian Federation Clinical Centre for Prevention and Control of AIDS ( Site 0504) Krasnodar Krasnodarskiy Kray
Russian Federation Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 0507) Krasnoyarsk Krasnoyarskiy Kray
Russian Federation Infectious Clinical Hospital #2 ( Site 0501) Moscow Moskva
Russian Federation FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 0500) Saint Petersburg Sankt-Peterburg
South Africa FARMOVS PTY LTD ( Site 0601) Bloemfontein Free State
South Africa Family Clinic Research With UBUNTU ( Site 0605) Cape Town Western Cape
South Africa King Edward Hospital ( Site 0600) Durban Kwazulu-Natal
South Africa Empilweni Services and Research Unit ( Site 0604) Johannesburg Gauteng
South Africa Perinatal HIV Research Unit ( Site 0602) Johannesburg Gauteng
South Africa Wits Reproductive Health and HIV Institute (WRHI) ( Site 0603) Johannesburg Gauteng
South Africa Be Part Yoluntu Centre ( Site 0606) Paarl Western Cape
Thailand Siriraj Hospital ( Site 0901) Bangkok Krung Thep Maha Nakhon
Thailand Research Institute for Health Sciences ( Site 0902) Chiang Mai
Thailand Faculty of Medicine - Khon Kaen University ( Site 0903) Khon Kaen
United States Emory Children's Center ( Site 0103) Atlanta Georgia
United States University of Colorado at Denver ( Site 0108) Aurora Colorado

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Mexico,  Russian Federation,  South Africa,  Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Area under the concentration-time curve from 0 to 24 hours postdose (AUC0-24hr) of DOR with 2 NRTIs in plasma at steady-state Plasma AUC0-24 hr of DOR with 2 NRTIs will be determined at steady-state. Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
Primary Maximum concentration (Cmax) of DOR with 2 NRTIs in plasma at steady-state Plasma Cmax of DOR with 2 NRTIs will be determined at steady-state. Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
Primary Concentration at 24 hours (C24) of DOR with 2 NRTIs in plasma at steady-state Plasma C24 of DOR with 2 NRTIs will be determined at steady-state. 24 hours postdose on Day 42
Primary Time to maximum concentration (Tmax) of DOR with 2 NRTIs in plasma at steady-state Plasma Tmax of DOR with 2 NRTIs will be determined at steady-state. Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
Primary Percentage of participants with =1 adverse event (AE) An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 24 weeks
Primary Percentage of participants with a Grade 3 or 4 AE Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated (Grade 3), or "potentially life-threatenting events" (Grade 4). Up to 24 weeks
Primary Percentage of participants with overall mortality The percentage of participants with mortality through 24 weeks will be determined. Up to 24 weeks
Primary Percentage of participants discontinuing from study treatment due to an AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 24 weeks
Primary Percentage of participants discontinuing from study treatment due to a drug-related AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to DOR. Up to 24 weeks
Secondary Plasma concentration of DOR The DOR plasma concentration will be determined with sparse PK sampling. Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
Secondary Plasma concentration of 3TC The 3TC plasma concentration will be determined with sparse PK sampling. Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
Secondary Plasma concentration of TFV The TFV plasma concentration will be determined with sparse PK sampling. Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
Secondary AUC0-24hr of 3TC Plasma AUC0-24 hr of 3TC will be determined at steady-state. Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
Secondary AUC0-24hr of TFV Plasma AUC0-24 hr of TFV will be determined at steady-state. Predose and 1, 2, 4, 12, and 24 hours postdose on Day 42
Secondary Cmax of 3TC Plasma Cmax of 3TC will be determined. Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
Secondary Cmax of TFV Plasma Cmax of TFV will be determined. Day 1 predose, Week 4 predose, Week 8 random, Week 12 random, and Week 24 predose and 0.5-2 hours postdose
Secondary Percentage of participants with =1 AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 48 weeks
Secondary Percentage of participants with =1 AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 96 weeks
Secondary Percentage of participants with Grade 3 or 4 AE Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated (Grade 3), or "potentially life-threatenting events" (Grade 4). Up to 48 weeks
Secondary Percentage of participants with Grade 3 or 4 AE Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated (Grade 3), or "potentially life-threatenting events" (Grade 4). Up to 96 weeks
Secondary Percentage of participants with overall mortality The percentage of participants with mortality through 48 weeks will be determined. Up to 48 weeks
Secondary Percentage of participants with overall mortality The percentage of participants with mortality through 96 weeks will be determined. Up to 96 weeks
Secondary Percentage of participants discontinuing from study treatment due to AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 48 weeks
Secondary Percentage of participants discontinuing from study treatment due to AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to 96 weeks
Secondary Percentage of participants discontinuing from study treatment due to drug-related AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to DOR. Up to 48 weeks
Secondary Percentage of participants discontinuing from study treatment due to drug-related AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to DOR. Up to 96 weeks
Secondary Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Up to 24 weeks
Secondary Percentage of participants with HIV-1 RNA <50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 48 weeks
Secondary Percentage of participants with HIV-1 RNA <50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 96 weeks
Secondary Percentage of participants with HIV-1 RNA <200 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 24 weeks
Secondary Percentage of participants with HIV-1 RNA <200 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 48 weeks
Secondary Percentage of participants with HIV-1 RNA <200 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 96 weeks
Secondary Percentage of virologically-suppressed (VS) participants with HIV-1 RNA =50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 24 weeks
Secondary Percentage of VS participants with HIV-1 RNA =50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 48 weeks
Secondary Percentage of VS participants with HIV-1 RNA =50 copies/mL Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Up to 96 weeks
Secondary Percentage of treatment-naive (TN) participants with log10 change from baseline in HIV-1 RNA Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 24
Secondary Percentage of TN participants with log10 change from baseline in HIV-1 RNA Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 48
Secondary Percentage of TN participants with log10 change from baseline in HIV-1 RNA Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 96
Secondary Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 24
Secondary Change from baseline in CD4+ T-cell counts Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 48
Secondary Change from baseline in CD4+ T-cell counts Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL. Day 1 and Week 96
Secondary Viral resistance-associated substitutions (RASs) to DOR or other treatment components The presence of viral RASs to DOR or other treatment components will be monitored for up to 96 weeks. Up to 96 weeks
Secondary Percentage of participants adhering to DOR treatment regimen Adherence to DOR will be monitored for up to 96 weeks. Up to 96 weeks
Secondary Assessment of palatability/acceptability of DOR pellets/granules Palatability/acceptability will be based on scores on the 5-point facial hedonic scale (FHS). FHS scores will be tabulated, and summarized by mean and SD, on Day 28. The highest possible FHS score is 5, with higher scores indicative of greater palatability. Day 28
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