Ignite Creation Date:
2024-05-06 @ 4:53 PM
Last Modification Date:
2024-10-26 @ 2:18 PM
Study NCT ID:
NCT05122767
Status:
RECRUITING
Last Update Posted:
2024-03-18
First Post:
2021-08-09
Brief Title:
Rifapentine and Isoniazid TB Preventive Therapy 3HP for Children Taking Dolutegravir-based Antiretroviral Treatment DOLPHIN KIDS
Sponsor:
The Aurum Institute NPC
Organization:
The Aurum Institute NPC
Study Overview
Official Title:
Safety Tolerability and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Once-weekly Rifapentine and Isoniazid 3HP Among Infants Children and Adolescents Living With HIV Taking Dolutegravir-based Antiretroviral Treatment
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DOLPHIN KIDS
Brief Summary:
Single-arm multi-center Phase III clinical trial in two groups Individuals with HIV infection taking Efavirenz EFV nevirapine NVP or lopinavirritonavir LPVr and two nucleoside reverse transcriptase inhibitors NRTI who have undetectable HIV viral load VL 50 copiesmL and an indication for tuberculosis TB preventive treatment TPT will be switched to dolutegravir DTG with tenofoviremtricitabine TDFFTC tenofovirlamivudine TDF3TC abacavirlamivudine ABC3TC or zidovudinelamivudine AZT3TC in accordance with South African National HIV Guidelines Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG Individuals who are on an existing DTG-based plus two NRTI antiretroviral therapy ART regimen for at least four weeks and have not received efavirenz or nevirapine or lopinavirritonavir for at least four weeks who have an undetectable HIV viral load may also participate
Detailed Description:
Group 1a n15 15 participants aged 2-17 years of age will have suppressed viral load and take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors NRTIs from Days 1-28 Semi-intensive pharmacokinetic PK sampling for dolutegravir will be performed on Day 28 Participants start twice-daily dolutegravir and will receive once-weekly rifapentine RPT and isoniazid INH 3HP for 12 total doses beginning on Day 29 Semi-intensive PK sampling for dolutegravir will be performed on Day 46 3 days after the 3rd dose of HP Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 PK assessments will not be performed for isoniazid given that its a well-studied drug in children VL will be measured at baseline week 0 and week 7 after 3 doses of 3HP and week 24 8 weeks after the last dose of 3HP Safety labs complete blood count CBC urea and electrolytes UE creatinine and liver function tests LFT will be obtained at baseline week 0 and weeks 4 7 12 16 20 and 24
Interim analysis will occur when all Group 1a participants have completed the 7-week semi-intensive PK visit HP week 3 Enrolment into Group 2a but not group 1b will commence once this interim analysis is complete Enrolment into group 1b will not be paused during this interim analysis The interim analysis will assess PK safety and VL data PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP The subsequent 30-45 participants age 2-17 years of age in Group 2a will receive twice or once-daily dosing of DTG respectively depending on PK modeling results
Group 1b n8 All participants less than 2 years of age with a suppressed viral load will take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors NRTIs from Days 1-28 Semi-intensive PK sampling for dolutegravir will be performed on Day 28 Participants start twice-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 29 Semi-intensive PK sampling for dolutegravir will be performed on Day 46 3 days after the 3rd dose of HP Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 PK assessments will not be performed for isoniazid given that its a well-studied drug in children VL will be measured at baseline week 0 and weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE creatinine and liver function tests LFT will be obtained at baseline week 0 and weeks 4 7 12 16 20 and 24
Interim analysis will occur when all Group 1b participants have completed the 7-week semi-intensive PK visit HP week 3 Enrolment into group 2b but not group 2a will commence once this interim analysis is complete Enrolment into group 2a will not be paused during this interim analysis Interim analysis will assess PK safety and VL data PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP The subsequent 16-24 participants in group 2b will receive twice or once-daily dosing of DTG respectively depending on population PK modeling results in this interim group
Group 1b may or may not occur in parallel with Group 1a This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger
Group 2a n45 or 30 In the case where we proceed with evaluating once-daily DTG with 3HP in children 2-17 years of age an additional 45 participants with suppressed viral load will be enrolled In the case where we proceed with evaluating twice-daily DTG dosing with 3HP an additional 30 participants with suppressed viral load will be enrolled Both groups will take dolutegravir once daily from days 1-28 weeks 1-4 On day 28 semi-intensive PK sampling for dolutegravir will be performed prior to any HP dose On day 29 week 5 participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily based on group 1a data and the first of the 12 HP weekly weight-based HP doses will be provided Semi-intensive PK sampling for DTG will be performed on day 46 2-4 days post third HP dose Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 Viral load will be measured at baseline screening week 0 and at weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline screening week 0 and weeks 4 7 12 16 20 and 24 Analysis will occur when 30 participants in the case of twice daily DTG dosing or 45 participants in the case of once daily DTG dosing have all completed the Week 24 visit
Group 2a will occur following interim results from Group 1a but may proceed without results from Group 1b
Group 2b n24 or 16 In the case where we proceed with evaluating once daily DTG with 3HP in children less than 2 years of age an additional 24 participants with suppressed viral load will be enrolled In the case where we proceed with evaluating twice daily DTG dosing with 3HP an additional 16 participants less than 2 years of age with suppressed viral load will be enrolled Both groups would take dolutegravir once daily from days 1-28 weeks 1-4 On day 28 semi-intensive PK sampling for dolutegravir will be performed prior to any HP dose On day 29 week 5 participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily based on group 1a and group 1b data and the first of the 12 HP weekly weight-based HP doses will be provided Semi-intensive PK sampling for DTG will be performed on day 46 3 days post third HP dose Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 Viral load will be measured at baseline screening week 0 and at weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline screening week 0 and weeks 4 7 12 16 20 and 24 Analysis will occur when 16 participants in the case of twice-daily DTG dosing or 24 participants in the case of once-daily DTG dosing have all completed the Week 24 visit
Group 2b will follow Group 1b and may or may not occur in parallel with Group 2a This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger
Interim analysis will occur when all Group 1a participants have completed the 7-week semi-intensive PK visit HP week 3 Enrolment into Group 2a but not group 1b will commence once this interim analysis is complete Enrolment into group 1b will not be paused during this interim analysis The interim analysis will assess PK safety and VL data PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP The subsequent 30-45 participants age 2-17 years of age in Group 2a will receive twice or once-daily dosing of DTG respectively depending on PK modeling results
Group 1b n8 All participants less than 2 years of age with a suppressed viral load will take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors NRTIs from Days 1-28 Semi-intensive PK sampling for dolutegravir will be performed on Day 28 Participants start twice-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 29 Semi-intensive PK sampling for dolutegravir will be performed on Day 46 3 days after the 3rd dose of HP Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 PK assessments will not be performed for isoniazid given that its a well-studied drug in children VL will be measured at baseline week 0 and weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE creatinine and liver function tests LFT will be obtained at baseline week 0 and weeks 4 7 12 16 20 and 24
Interim analysis will occur when all Group 1b participants have completed the 7-week semi-intensive PK visit HP week 3 Enrolment into group 2b but not group 2a will commence once this interim analysis is complete Enrolment into group 2a will not be paused during this interim analysis Interim analysis will assess PK safety and VL data PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP The subsequent 16-24 participants in group 2b will receive twice or once-daily dosing of DTG respectively depending on population PK modeling results in this interim group
Group 1b may or may not occur in parallel with Group 1a This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger
Group 2a n45 or 30 In the case where we proceed with evaluating once-daily DTG with 3HP in children 2-17 years of age an additional 45 participants with suppressed viral load will be enrolled In the case where we proceed with evaluating twice-daily DTG dosing with 3HP an additional 30 participants with suppressed viral load will be enrolled Both groups will take dolutegravir once daily from days 1-28 weeks 1-4 On day 28 semi-intensive PK sampling for dolutegravir will be performed prior to any HP dose On day 29 week 5 participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily based on group 1a data and the first of the 12 HP weekly weight-based HP doses will be provided Semi-intensive PK sampling for DTG will be performed on day 46 2-4 days post third HP dose Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 Viral load will be measured at baseline screening week 0 and at weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline screening week 0 and weeks 4 7 12 16 20 and 24 Analysis will occur when 30 participants in the case of twice daily DTG dosing or 45 participants in the case of once daily DTG dosing have all completed the Week 24 visit
Group 2a will occur following interim results from Group 1a but may proceed without results from Group 1b
Group 2b n24 or 16 In the case where we proceed with evaluating once daily DTG with 3HP in children less than 2 years of age an additional 24 participants with suppressed viral load will be enrolled In the case where we proceed with evaluating twice daily DTG dosing with 3HP an additional 16 participants less than 2 years of age with suppressed viral load will be enrolled Both groups would take dolutegravir once daily from days 1-28 weeks 1-4 On day 28 semi-intensive PK sampling for dolutegravir will be performed prior to any HP dose On day 29 week 5 participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily based on group 1a and group 1b data and the first of the 12 HP weekly weight-based HP doses will be provided Semi-intensive PK sampling for DTG will be performed on day 46 3 days post third HP dose Additional sparse PK sampling for dolutegravir trough concentrations CT will be performed on Days 44 and 48 Semi-intensive PK sampling for RPT will be performed on day 78 Viral load will be measured at baseline screening week 0 and at weeks 7 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline screening week 0 and weeks 4 7 12 16 20 and 24 Analysis will occur when 16 participants in the case of twice-daily DTG dosing or 24 participants in the case of once-daily DTG dosing have all completed the Week 24 visit
Group 2b will follow Group 1b and may or may not occur in parallel with Group 2a This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None