Back to resultsDTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old (D3 (Penta21))
Primary Purpose
HIV Infections
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dolutegravir (DTG) and lamivudine (3TC)
SOC
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
- HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
- Aged 2 to <15 years old
- Weight 6 kg or higher
- Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
- Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
- Girls who are sexually active must be willing to adhere to highly effective methods of contraception
- A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol
- Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study
Exclusion Criteria:
- Any previous switch in ART regimen for virological, immunological or clinical treatment failure
- Any changes in ART in the last 6 months for reasons other than due to child's growth, drug stock-outs, changes in country guidelines and treatment simplification
- Evidence of previous resistance to 3TC or INSTI
- Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
- Known allergy or contraindications to dolutegravir or lamivudine
- Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
- Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)
- Randomisation visit more than 12 weeks after the most recent screening visit
- Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
- Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
- Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)
- Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
- Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Screening creatinine clearance <50 mL/min/1.73m2
- Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
- Girls who are pregnant or breastfeeding
- Children who are in the legal custody of the State and do not have a parent or guardian able to provide informed consent on their behalf.
Sites / Locations
- King Edward VIII HospitalRecruiting
- PHRU KlerksdorpRecruiting
- PHRURecruiting
- Hospital Universitario 12 de Octubre
- Prapokklao HospitalRecruiting
- Nakornping HospitalRecruiting
- Chiangrai Prachanukroh HospitalRecruiting
- Khon Kaen HospitalRecruiting
- BaylorRecruiting
- Joint Clinical Research CentreRecruiting
- MUJHURecruiting
- Birmingham Heartlands Hospital
- Great Ormand Street Hospital
- St. Mary's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
SOC
DTG/3TC
Arm Description
Standard-of-care (SOC)
Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC)
Outcomes
Primary Outcome Measures
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
Secondary Outcome Measures
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Time to any new or recurrent WHO 3 or WHO 4 event or death
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events
Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Proportion of children with a change in ART for toxicity or switch to second-line
Change in blood lipids from baseline to weeks 48 and 96
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Full Information
NCT ID
NCT04337450
First Posted
March 27, 2020
Last Updated
September 15, 2023
Sponsor
PENTA Foundation
Collaborators
MRC CTU at UCL, AMS-CMU/IRD (PHPT), Chris Hani Baragwanath Academic Hospital, Durban International Clinical Research Site, Hospital Universitario 12 de Octubre, Prapokklao Hospital, Chantaburi, Chiangrai Prachanukroh Hospital, Nakornping Hospital, Khon Kaen Hospital, Kalasin Hospital, Kalasin, Chiang Mai University, Joint Clinical Research Center, MU-JHU CARE, Baylor College of Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Imperial College Healthcare Trust, St Mary's Hospital, Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands., Advanced Pathogens Diagnostics Unit, University College London Hospitals, Centre for Health Economics, University of York, Department of Molecular and Clinical Pharmacology, University of Liverpool
1. Study Identification
Unique Protocol Identification Number
NCT04337450
Brief Title
DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
Acronym
D3 (Penta21)
Official Title
A Randomised Non-inferiority Trial With Nested PK to Assess DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 22, 2022 (Actual)
Primary Completion Date
September 15, 2024 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PENTA Foundation
Collaborators
MRC CTU at UCL, AMS-CMU/IRD (PHPT), Chris Hani Baragwanath Academic Hospital, Durban International Clinical Research Site, Hospital Universitario 12 de Octubre, Prapokklao Hospital, Chantaburi, Chiangrai Prachanukroh Hospital, Nakornping Hospital, Khon Kaen Hospital, Kalasin Hospital, Kalasin, Chiang Mai University, Joint Clinical Research Center, MU-JHU CARE, Baylor College of Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Imperial College Healthcare Trust, St Mary's Hospital, Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands., Advanced Pathogens Diagnostics Unit, University College London Hospitals, Centre for Health Economics, University of York, Department of Molecular and Clinical Pharmacology, University of Liverpool
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study aims to find out whether treating children and young people living with HIV with two anti HIV medicines, dolutegravir and lamivudine, is safe and as effective as the three-medicine anti-HIV treatments currently used in routine practice.
Detailed Description
This study will include 370 children and young people aged 2 to less than 15 years old who are living with HIV and are being treated with anti-HIV medicines for the first time. Participants will be split into two groups, by chance, by a process called "randomisation". One group will continue to receive the anti-HIV medicines already taken according to country-specific routine practice. The second group will change to the new combination of medicine, dolutegravir and lamivudine (with the combination written usually as "DTG/3TC"). Depending on the weight, participants in the second group will be able take the new medicine either as one tablet a day or as a small number of dispersible tablets that are also taken once a day. All children and young people in the study will have regular clinic assessments that are at a similar frequency to the clinic visits that participants would have outside of the study. Blood tests will be performed to check that the medicine is safe and, at some visits, participants and their carers will also be asked to answer some questions on how they feel about taking their medicine. All children and young people will be followed until the last participant who joins the study has been in the study for 96 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
370 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SOC
Arm Type
Active Comparator
Arm Description
Standard-of-care (SOC)
Arm Title
DTG/3TC
Arm Type
Experimental
Arm Description
Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC)
Intervention Type
Drug
Intervention Name(s)
Dolutegravir (DTG) and lamivudine (3TC)
Intervention Description
Children randomised to the DTG/3TC arm will receive once daily DTG/3TC fixed dose combination dispersible or film-coated tablets dosed using WHO weight bands criteria
Intervention Type
Drug
Intervention Name(s)
SOC
Intervention Description
2 nucleos(t)ide reverse transcriptase inhibitor (NRTI) and a third (anchor) drug (either an integrase strand transfer inhibitor (INSTI), a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI)
Primary Outcome Measure Information:
Title
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
Time Frame
by Week 96
Secondary Outcome Measure Information:
Title
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48
Time Frame
by Week 48
Title
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Time Frame
at Week 48 and 96
Title
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
Time Frame
at Week 24, 48 and 96
Title
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Time Frame
by Week 96
Title
Time to any new or recurrent WHO 3 or WHO 4 event or death
Time Frame
through study completion, up to 5 years
Title
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Time Frame
Week 24, 48 and 96
Title
Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events
Time Frame
through study completion, up to 5 years
Title
Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Time Frame
through study completion, up to 5 years
Title
Proportion of children with a change in ART for toxicity or switch to second-line
Time Frame
through study completion, up to 5 years
Title
Change in blood lipids from baseline to weeks 48 and 96
Time Frame
Week 48 and 96
Title
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Time Frame
Week 48 and 96
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
Aged 2 to <15 years old
Weight 6 kg or higher
Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
Girls who are sexually active must be willing to adhere to highly effective methods of contraception
A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol
Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study
Exclusion Criteria:
Any previous switch in ART regimen for virological, immunological or clinical treatment failure
Any changes in ART in the last 6 months for reasons other than due to child's growth, drug stock-outs, changes in country guidelines and treatment simplification
Evidence of previous resistance to 3TC or INSTI
Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
Known allergy or contraindications to dolutegravir or lamivudine
Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)
Randomisation visit more than 12 weeks after the most recent screening visit
Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)
Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
Screening creatinine clearance <50 mL/min/1.73m2
Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
Girls who are pregnant or breastfeeding
Children who are in the legal custody of the State and do not have a parent or guardian able to provide informed consent on their behalf.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Turkova, MSc
Phone
+4402076704658
Email
a.turkova@ucl.ac.uk
Facility Information:
Facility Name
King Edward VIII Hospital
City
Durban
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moherndran Archary
Email
archary@ukzn.ac.za
Facility Name
PHRU Klerksdorp
City
Klerksdorp
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ebrahim Variava
Email
Variavae@phru.co.za
Facility Name
PHRU
City
Soweto
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Avy Violari
Email
violari@mweb.co.za
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pablo Rojo
Email
pablorojoconejo@netscape.net
Facility Name
Prapokklao Hospital
City
Chanthaburi
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chaiwat Ngampiyaskul
Email
chaiwat008@gmail.com
Facility Name
Nakornping Hospital
City
Chiang Mai
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suparat Kanjanavanit
Email
skanjanavanit@gmail.com
Facility Name
Chiangrai Prachanukroh Hospital
City
Chiang Rai
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pradthana Ounchanum
Email
doctorbaiplu@gmail.com
Facility Name
Khon Kaen Hospital
City
Khon Kaen
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ussanee Srirompotong
Email
u.srirompotong@gmail.com
Facility Name
Baylor
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adeodata Kekitiinwa
Email
akekitiinwa@baylor-uganda.org
Facility Name
Joint Clinical Research Centre
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cissy Kityo Mutuluuza
Email
ckityo@jcrc.org.ug
Facility Name
MUJHU
City
Kampala
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippa Musoke
Email
pmusoke@mujhu.org
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Welch
Email
steven.welch@heartofengland.nhs.uk
Facility Name
Great Ormand Street Hospital
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alasdair Bamford
Email
Alasdair.Bamford@gosh.nhs.uk
Facility Name
St. Mary's Hospital
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Foster
Email
caroline.foster5@nhs.net
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
https://penta-id.org/
Description
Related Info
URL
https://www.ctu.mrc.ac.uk/
Description
Related Info
Learn more about this trial
DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old
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