Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202112842892883 Date of Registration: 02/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title 205858
Official scientific title Open-label access to dolutegravir for HIV-1 infected children and adolescents completing IMPAACT Studies P1093 and P2019.
Brief summary describing the background and objectives of the trial DTG as an oral tablet formulation has been approved for the treatment of HIV infection in most countries around the world and is now recommended as a component of first line therapy in global treatment guidelines [DHHSa, 2019; EACS, 2018; WHO, 2018]. In addition to being marketed as the Tivicay™ single-entity film coated tablet and as Tivicay or Tivicay PD™ single entity dispersible tablet, DTG is also a component of the fixed-dose combination product Triumeq [DTG/abacavir (ABC)/lamivudine(3TC)]. ABC and 3TC form the backbone of several recommended ART regimens. These medications are available separately in tablet and liquid formulations and have also been co-formulated in fixed dose combination tablets (ABC/3TC). Previous experience in adults has demonstrated that the exposure to DTG, ABC and 3TC in a fixed dose combination formulation is consistent with each drug administered individually. This information was provided as part of the application for Triumeq™. Therefore, the DTG dosing recommendations are not expected to differ when DTG is administered in fixed dose combination. Parent Study P1093 (ING112578)- Single entity DTG (Tivicay™ and Tivicay PD™) Pediatric study P1093 (ING112578) is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) under sponsorship by the Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Study P1093 evaluates the safety, tolerability, PK and antiviral activity of DTG in ART- naïve and ART-experienced children and adolescents in various pediatric subsets defined by age and type of formulation. Types of formulations included in this study are film coated tablets, pediatric granules and dispersible tablets (DT). The DTG granule formulation is no longer being developed for licensure.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 10/03/2022
Actual trial start date
Anticipated date of last follow up 10/03/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 300
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Dolutegravir Age Weight Band (kg) Dose (mg) Dose (mg/kg) low weigh high weight ≥ 4 weeks to < 6 months of age 3 - <6 5 1.67 0.83 6 - <10 10 1.67 1.00 ≥ 6 months of age 3- < 6 10 3.33 1.67 6- <10 15 2.50 1.50 10 - <14 20 2.00 1.43 14 - <20 25 1.79 1.25 ≥20 30 1.50 4 years The purpose of this study is to provide continued access to IP for eligible subjects who have completed the parent studies and continue to benefit from IP administration as evidenced by virologic control at the time of completion of the parent studies. Subjects will receive their age/weight appropriate dose of IP as defined in the parent study; hence, no PK sampling will be performed. 300
Control Group Triumeq 6 to less than 10 kg 3 dispersible tablets (180/15/90 mg) 10 to less than 14 kg 4 dispersible tablets (240/20/120 mg) 14 to less than 20 kg 5 dispersible tablets (300/25/150 mg) 20 to less than 25 kg 6 dispersible tablets (360/30/180 mg) 25 kg or greater 1 immediate release tablet (600/50/300 mg) 4 years Two formulations of ABC/DTG/3TC will be utilized for subjects transitioning from the P2019 study. Immediate release tablets and dispersible tablets will be provided to subjects by weight bands. ABC/DTG/3TC tablets (60 mg/5 mg/30 mg dispersible tablets or 600 mg/50 mg/300 mg immediate release [Triumeq™] tablets) will be provided to subjects by age and weight bands. 300 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Subjects must have completed participation in one of the following parent studies, for the duration noted: P1093 parent study through at least Week 180 P2019 parent study through at least Week 48 Virological control at screening: a) Subjects in parent study P1093 must have virological control defined as HIV- 1 RNA <400 c/mL at their penultimate visit (on or after the Week 180 visit). b) Subjects in parent study P2019 must have virological control defined as HIV- 1 RNA <200 c/mL at their penultimate visit (on or after Week 36). Note: If the penultimate P1093 or P2019 visit (on or after Week 180 for P1093; on or after Week 36 for P2019) indicates the possibility of virologic failure, a single retest can be completed in the parent study. – Results of the retest must be obtained and confirmed prior to the Day 1 visit (the Day 1 visit overlaps with the final visit in each parent study). – If the retest indicates virologic control is present as noted above, eligibility is confirmed as long as the participant meets all other entry criteria. – Adherence issues should be addressed, and viral suppression must be confirmed prior to Day 1. Evidence of continued benefit from IP during the subject’s participation in the parent study (P1093 or P2019). – At screening, Investigators will submit a clinical summary verifying evidence of continued benefit from IP during the subject’s participation in the parent study (P1093 or P2019). – The summary will be submitted via the PPD ePIP system to the Study Medical Monitor who will review and confirm if the inclusion criterion has been met. – Confirmation from the Study Medical Monitor is required to meet this eligibility criterion 4. Males and Females All subjects who are engaging in sexual activity should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g. male Confirmed virologic failure with evidence of resistance to: a) DTG in the P1093 parent study, or b) ABC, DTG or 3TC (with the exception of M184V) in the P2019 parent study 2. Presence of any active Acquired Immunodeficiency Syndrome (AIDS) defining opportunistic infection. 3. Known ≥Grade 3 laboratory toxicities within 30 days prior to study entry (e.g. neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), ALT, lipase, serum creatinine and total bilirubin). Repeat testing is allowed for eligibility determination. NOTE: ≥Grade 3 total bilirubin is allowable, if the subject is on ATV. NOTE: Subjects with laboratory abnormalities considered unrelated to IP may be allowed to enter the study. Thus, if the laboratory abnormality persists upon repeat testing, the subject may be considered for study entry after consultation and approval of the study team. 4. Previous permanent discontinuation from IP in the parent study due to toxicity, intolerance, or pregnancy. Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 2 Year(s) 7 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 22/10/2021 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Mbagathi Way, 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Study drug will be provided until age-appropriate formulations receive local regulatory approval and are commercially available or are available from some other source (e.g. government programs, aid programs etc) or until the subject no longer derives benefit from treatment or until a subject meets a protocol defined reason for discontinuation or until development of DTG or ABC/DTG/3TC is terminated. 5 years
Secondary Outcome To assess any serious adverse events (SAEs) and any clinical or laboratory adverse events that lead to the discontinuation of IP (DTG or ABC/DTG/3TC FDC). 5 years.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute Kericho 1357 Kericho 20200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
ViiV Healthcare 980 Great West Road Middlesex. TW8 9GS, United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor ViiV Healthcare UK Limited 980 Great West Road Middlesex TW8 9GS, United Kingdom Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Dr Ounchanum 187 Road Changklan Muang 50100 Thailand
Dr Pinto 190 Av. Prof. Alfredo Balena Belo Horizonte 30130,100 Brazil
Dr Patricia 262 Danny Thomas Place Memphis 38105 United States of America
Dr Cotton Site 8950Ward Cape Town 7505 South Africa
Dr Lee Shandukani Research 2nd Floor Hillbrow 2001 South Africa
Dr Moherndran 1358 Mangosuthu Highway Umlazi 4066 South Africa
Dr Liberty Chris Hani Road Johannesburg 1862 South Africa
Dr Aurpibul RIHES Building Muang 50200 Thailand
Dr Chokephaibulkit 2 Wanglang Road Bangkok 10700 Thailand
Dr Koech Hospital Road Kericho 20200 Kenya
Dr Pilotto venida Henrique Duque Estrada Mayer, 953 Nova Iguacu 26030-381 Brazil
Dr Mussi Avenida Bandeirantes 3900 Preto 14048-900 Brazil
Dr Oliveira Ricardo Hugo Rua Bruno Lobo, 50 Rio de Janeiro 21941-91 Brazil
Dr Deville Jaime Le Conte Avenue MDCC 22-442 Los Angeles 90095 United States of America
Dr Mutsawashe Filda Mazowe Street Harare 263 Zimbabwe
Dr Blandina Mmbaga Sokoine Road Moshi 412105 United Republic of Tanzania
Dr Masheto Plot 2731 Hospital Way Gaborone Botswana
Dr Philippa Upper Mulago Hill Road Kampala Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Clinical Disclosure Advisor Clinical Disclosure Adviso GSKClinicalSupportHD@gsk.com 001877393718 Rue de Institut,89
City Postal code Country Position/Affiliation
Rixensart 1330 Ghana Clinical Disclosure Advisor
Role Name Email Phone Street address
Scientific Enquiries Clinical Disclosure Advisor Clinical Disclosure Advisor GSKClinicalSupportHD@gsk.com 0018773793718 Rue de Institut
City Postal code Country Position/Affiliation
Rixensart 1330 Belgium Clinical Disclosure Advisor
Role Name Email Phone Street address
Public Enquiries Clinical Disclosure Advisor Clinical Disclosure Advisor GSKClinicalHD@gsk.com 0018773793718 Rue de Institut,89
City Postal code Country Position/Affiliation
Rixensart 1330 Belgium Clinical Disclosure Advisor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The trial result summary will be shared when the final clinical study report is available. The method of sharing information will be determined for the study and information updated. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol When the clinical study report is final To be confirmed
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information