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| ID | Type | Description | Link |
|---|---|---|---|
| MK-1439-066 | Other Identifier | MSD | |
| 2019-003955-13 | EudraCT Number |
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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:
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDF | Experimental | Participants receive doravirine (DOR) at 7.2 mg to 100 mg, based on weight, PLUS 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs), based on local label, for 96 weeks, OR a fixed-dose combination (FDC) of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), based on weight, for 96 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doravirine | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Per protocol, intensive pharmacokinetic (PK) sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine C24. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Tmax. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine AUC0-12hr. | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentration of DOR | Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks. | 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) |
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Inclusion Criteria:
Study Extension Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Toll Free Number | Contact | 1-888-577-8839 | Trialsites@msd.com |
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado at Denver ( Site 0108) | Completed | Aurora | Colorado | 80045 | United States | |
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| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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| 2 NRTIs | Drug | Administered orally |
|
| DOR/3TC/TDF | Drug | Administered orally |
|
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| Cmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Cmax. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine C12. | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose |
| Tmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Tmax. | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose |
| 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 interventions. | Up to 24 weeks |
| 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-threatening events" (Grade 4). | Up to 24 weeks |
| Percentage of Participants With Events of Death | The percentage of participants with events of death at Week 24 will be reported. | Up to 24 weeks |
| Percentage of Participants Discontinuing From Study Intervention 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 interventions. | Up to 24 weeks |
| Percentage of Participants Discontinuing From Study Intervention 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 the study interventions. | Up to 24 weeks |
Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks. |
| 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 | Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr of 3TC. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr of TFV. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of 3TC. | 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of TFV. | Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose |
| Percentage of Participants With ≥1 AE at Week 48 | 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 interventions. | Up to 48 weeks |
| Percentage of Participants With ≥1 AE at Week 96 | 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 interventions. | Up to 96 weeks |
| Percentage of Participants With Grade 3 or 4 AE at Week 48 | 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-threatening events" (Grade 4). | Up to 48 weeks |
| Percentage of Participants With Grade 3 or 4 AE at Week 96 | 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-threatening events" (Grade 4). | Up to 96 weeks |
| Percentage of Participants With Events of Death at Week 48 | The percentage of participants with events of death at Week 48 will be reported. | Up to 48 weeks |
| Percentage of Participants With Events of Death at Week 96 | The percentage of participants with events of death at Week 96 will be reported. | Up to 96 weeks |
| Percentage of Participants Discontinuing From Study Intervention Due to AE at Week 48 | 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 interventions. | Up to 48 weeks |
| Percentage of Participants Discontinuing from Study Intervention Due to AE at Week 96 | 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 interventions. | Up to 96 weeks |
| Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 48 | 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 the study interventions. | Up to 48 weeks |
| Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 96 | 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 the study interventions. | Up to 96 weeks |
| Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24 | 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 |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 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 |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | 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 |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 24 | 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 |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | 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 |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | 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 |
| Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24 | 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 |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 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 |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96 | 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 |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 24 | 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. | Baseline (Day 1) and Week 24 |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 48 | 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. | Baseline (Day 1) and Week 48 |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 96 | 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. | Baseline (Day 1) and Week 96 |
| Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 24 | CD4+ T-cell counts will be performed at the central laboratory. | Baseline (Day 1) and Week 24 |
| Change From Baseline in CD4+ T-Cell Counts at Week 48 | CD4+ T-cell counts will be performed at the central laboratory. | Baseline (Day 1) and Week 48 |
| Change From Baseline in CD4+ T-Cell Counts at Week 96 | CD4+ T-cell counts will be performed at the central laboratory. | Baseline (Day 1) and Week 96 |
| 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 |
| Percentage of Participants Adhering to DOR or to the FDC of DOR/3TC/TDF | Adherence to DOR or to the FDC of DOR/3TC/TDF will be monitored for up to 96 weeks. | Up to 96 weeks |
| Assessment of Palatability/Acceptability of Oral Pellets/Granules of DOR or the FDC of DOR/3TC/TDF | 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 standard deviation (SD), on Day 28. The highest possible FHS score is 5, with higher scores indicative of greater palatability. | Day 28 |
| Emory Children's Center ( Site 0103) |
| Recruiting |
| Atlanta |
| Georgia |
| 30322 |
| United States |
|
| Clinica Somer ( Site 1003) | Recruiting | Rionegro | Antioquia | 054040 | Colombia |
|
| Ciensalud Ips S A S ( Site 1001) | Recruiting | Barranquilla | Atlántico | 080020 | Colombia |
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| CEIP - Centro de Estudios en InfectologÃa Pediátrica ( Site 1002) | Completed | Cali | Valle del Cauca Department | 760042 | Colombia |
| Instituto Nacional de Pediatria ( Site 0701) | Completed | Coyoacán | Mexico City | 04530 | Mexico |
| Hospital Infantil de Mexico Federico Gomez ( Site 0702) | Active, not recruiting | Mexico City | Mexico City | 06720 | Mexico |
| Unidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700) | Completed | Mérida | Yucatán | 97000 | Mexico |
| Kuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506) | Active, not recruiting | Kemerovo | Kemerovo Oblast | 650056 | Russia |
| Clinical Centre for Prevention and Control of AIDS ( Site 0504) | Completed | Krasnodar | Krasnodarskiy Kray | 350015 | Russia |
| Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 0507) | Completed | Krasnoyarsk | Krasnoyarsk Krai | 660049 | Russia |
| Infectious Clinical Hospital #2 ( Site 0501) | Completed | Moscow | Moscow | 105275 | Russia |
| FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 0500) | Active, not recruiting | Saint Petersburg | Sankt-Peterburg | 196645 | Russia |
| FARMOVS PTY LTD ( Site 0601) | Completed | Bloemfontein | Free State | 9301 | South Africa |
| Perinatal HIV Research Unit ( Site 0602) | Recruiting | Johannesburg | Gauteng | 1864 | South Africa |
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| Wits Reproductive Health and HIV Institute (WRHI) ( Site 0603) | Recruiting | Johannesburg | Gauteng | 2001 | South Africa |
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| Empilweni Services and Research Unit ( Site 0604) | Completed | Johannesburg | Gauteng | 2093 | South Africa |
| King Edward Hospital ( Site 0600) | Recruiting | Durban | KwaZulu-Natal | 4001 | South Africa |
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| Family Clinic Research With UBUNTU ( Site 0605) | Recruiting | Cape Town | Western Cape | 7505 | South Africa |
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| Be Part Yoluntu Centre ( Site 0606) | Recruiting | Paarl | Western Cape | 7626 | South Africa |
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| Tsitsikamma Clinical Research Initiative (TCRI) ( Site 0607) | Completed | Plettenberg Bay | Western Cape | 6600 | South Africa |
| Siriraj Hospital ( Site 0901) | Recruiting | Bangkok | Bangkok | 10700 | Thailand |
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| Research Institute for Health Sciences ( Site 0902) | Recruiting | Chiang Mai | 50200 | Thailand |
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| Faculty of Medicine - Khon Kaen University ( Site 0903) | Recruiting | Khon Kaen | 40002 | Thailand |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000592662 | doravirine |
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