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.: PACTR202007806554538 Date of Registration: 10/07/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PharmacokinEtic and safeTy of the 4-In-1 granules in neonaTEs: PETITE Study
Official scientific title Open label, single arm, two-stage trial to evaluate the single and multi-dose pharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10mg) (4-in-1) fixed-dose granule formulation in HIV-exposed neonates
Brief summary describing the background and objectives of the trial In December 2018, the WHO-led expert group responsible for prioritizing paediatric antiretroviral drugs and formulations (PADO) indicated as a high priority the need to assess the use of the new 4-in-1 formulation (ABC/3TC/LPV/r or Quadrimune) in HIV-exposed and infected neonates. The PETITE study has thus been developed to directly address this research gap to assess the safety and pharmacokinetics of ABC/3TC/LPV/r when administering Quadrimune to HIV-exposed neonates with a birth weight of ≥ 2000 to 4000 g. Study Objectives: Primary Objectives • To evaluate the safety of ABC, 3TC and LPV/r during the first 28 days of life in HIV-exposed neonates following administration of Quadrimune • To determine the pharmacokinetics of ABC, 3TC and LPV/r during the first 28 days of life in HIV-exposed neonates following administration of Quadrimune Secondary Objective • To assess the acceptability of Quadrimune for the neonate and the caregiver
Type of trial CCT
Acronym (If the trial has an acronym then please provide) PETITE
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Pharmacokinetics and Safety
Anticipated trial start date 01/07/2020
Actual trial start date
Anticipated date of last follow up 31/07/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
DOH 2705208466 South African National Clinical Trial Registry
14420 Stellenbosch University Health Research Ethics Commitee
20200301 South African Health Products Regulatory Authority
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Quadrimune. Quadrimune formulation containins 30 mg of abacavir (ABC), 15 mg of 3TC, 40 mg of LPV and 10 mg of ritonavir. The total study duration (1st enrolment to last follow-up) will be 24 months. Cohort 1A will be accrued and followed over a period of 6 months, and Cohort 2 over a period of 18 months, respectively. Each individual participant in Cohort 1A, 1B and Cohort 2 will be followed for a minimum of 4, 5 and 6 weeks, respectively. Stage 1: Single Dose(s) of Quadrimune Any HIV-exposed neonates (pending HIV status) on standard of care ARV prophylaxis, will be stratified by birth weight, with Cohort 1A opening to accrual first • Stage 1 will assess single dose(s) of Quadrimune in two sequential cohorts: Cohort 1A (n=8) and Cohort 1B (n=8). 16
Experimental Group Quadrimune Quadrimune formulation containins 30 mg of abacavir (ABC), 15 mg of 3TC, 40 mg of LPV and 10 mg. The total study duration (1st enrolment to last follow-up) will be 24 months. Cohort 1A will be accrued and followed over a period of 6 months, and Cohort 2 over a period of 18 months, respectively. Each individual participant in Cohort 1A, 1B and Cohort 2 will be followed for a minimum of 4, 5 and 6 weeks, respectively. Stage 2: Multi-Dose of Quadrimune HIV-exposed neonates (pending HIV status) who are at high risk of perinatal HIV transmission (i.e., mothers on ARV drugs whose last available HIV RNA viral load (VL) during pregnancy was detectable (VL > 50 copies/mL) OR if no viral load result was available in the last 12 weeks of antenatal care) will be stratified by birth weight. Standard of care ARV prophylaxis will be interrupted during the administration of Quadrimune (for 4 weeks) and resumed following the completion of Quadrimune - if needed, as per local guidelines. Cohorts 2A and 2B will open at the same time: • Stage 2 will assess multi-doses of Quadrimune in a single cohort, stratified by birth weight: Cohort 2A, ≥ 3000 to 4000 g (n=17) and Cohort 2B, ≥ 2000 to < 3000 g (n=17). 34
Control Group NA N/A N/A N/A 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Written informed consent to participate in the study must be obtained for all participants from the parent(s) or legal guardian. In addition, for each cohort, the following Cohort Specific Inclusion Criteria must be met at Study Entry: Cohort 1A • HIV-exposed neonates (pending HIV status) on standard of care ARV prophylaxis, as per local guidelines • < 14 days of age • Birth weight of ≥2500 g to 4000 g Cohort 1B • HIV-exposed neonates (pending HIV status) on standard of care ARV prophylaxis, as per local guidelines • ≤ 3 days of age • Birth weight of ≥2000 to 4000 g Cohort 2 • HIV-exposed neonates (pending HIV status) who are at high risk of perinatal HIV transmission on standard of care ARV prophylaxis, as per local guidelines • ≤ 3 days of age • Birth weight of ≥2000 to 4000 g The presence of any of the following at entry, will exclude a subject from study enrolment: • Less than 37 weeks gestational age at birth • Baseline ECG has a QTc of > 0.45 sec • Haemoglobin value of < 13.0 g/dL • Hypokalemia (<3.6 mmol/L) • Hyperkalemia (>6.7 mmol/L) • Hyponatremia (<135 mmol/L) • Hypernatremia (>145 mmol/L) • A Creatinine value above the upper limit of normal for gestational age and postnatal age. • AST or ALT of more than 1.25 the upper limit of normal (ULN) • Total Bilirubin close to exchange value (based on local guidelines) or a high Bilirubin with red cell haemolysis • Any other Grade ≥3 event on the DAIDS toxicity table • Severe congenital abnormalities at investigator’s discretion • Receiving treatment for tuberculosis (TB) • Mothers on LPV-containing ARV treatment • Any medications known to induce QT interval prolongation • Critically ill infants at the discretion of the examining clinician • Participation in another clinical trial • HIV-infected neonates • Neonatal abstinence syndrome New born: 0 Day-1 Month 0 Day(s) 14 Day(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
Yes 07/05/2020 Stellenbosch University Health Research Ethics Comittee
Ethics Committee Address
Street address City Postal code Country
Francie van Zijl Drive Cape Town 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • Occurrence of the following events: adverse events of Grade 3 or higher; treatment-related adverse events of Grade 3 or higher; any adverse events • ABC, 3TC, LPV plasma pharmacokinetics parameters: area under the concentration time curve (AUC); maximum plasma concentration (Cmax), apparent clearance (CL/F), and trough concentration (Ctrough) Interim Analysis will be conducted after the last participant in Cohort 1A and 1B and after 50 percent have completed enrollment in Cohort 2 or early termination of the study.
Secondary Outcome • Acceptability to caregivers and neonates of using Quadrimune will be measured by means of a questionnaire At each pK visit.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Family Centre for Research with Ubuntu Francie van Zijl Drive Cape Town 7505 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Unitaid 40 Chemin du Pommier, 5th Floor, Grand-Saconnex Geneva 1218 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Stellenbosch University Tygerberg Hospital Francie van Zijl Avenue, Parow Valley Cape Town 7505 South Africa University
COLLABORATORS
Name Street address City Postal code Country
Dr Tim Cressey PHPT/IRD 174, Research Unit at Chiang Mai University Faculty of Associated Medical Sciences, Chiang Mai University, 110, Intrawarorot Road, Sripoom, Muang Chiang Mai Thailand
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Adrie Bekker adrie@sun.ac.za +270219389198 Faculty of Medicine and Health Sciences, Francie van Zijl Drive, Clinical Building, 2nd Floor, Tygerberg
City Postal code Country Position/Affiliation
Cape Town 7505 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Adrie Bekker adrie@sun.ac.za +270219389198 Faculty of Medicine and Health Sciences, Francie van Zijl Drive, Clinical Building, 2nd Floor, Tygerberg
City Postal code Country Position/Affiliation
Cape Town 7507 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Adrie Bekker adrie@sun.ac.za +27219389198 Faculty of Medicine and Health Sciences, Francie van Zijl Drive, Clinical Building, 2nd Floor, Tygerberg
City Postal code Country Position/Affiliation
Cape Town 7505 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Tim Cressey tim.cressey@phpt.org +66053894994 PHPT/IRD 174, Research Unit at Chiang Mai University Faculty of Associated Medical Sciences, Chiang Mai University, 110, Intrawarorot Road, Sripoom, Muang
City Postal code Country Position/Affiliation
Chang Mai Thailand CoPrincipal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified individual data reported in the primary manuscript can be shard upon request and agreement by the study team. Study Protocol No sharing time frame is available. Sharing of data can be requested and upon sponsor agreement it can be shared. There are no start and end dates to the availability thereof. Controlled access to data will be allowed upon approval of the request by the study team and agreement from the study sponsor.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://blogs.sun.ac.za/dttc/benefit-kids/ 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