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.: PACTR201903696308665 Date of Approval: 22/03/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Lopinavir/r/ Lamivudine/ Abacavir as an Easy to Use Paediatric Formulation (LOLIPOP)
Official scientific title Phase I/II, open label, randomized crossover pharmacokinetic, safety and acceptability study of the Abacavir/Lamivudine/ Lopinavir/Ritonavir/ - 30/15/ 40/10mg (4-in-1) Fixed-Dose Combination vs. Lopinavir/Ritonavir- 40/10mg pellets plus dual Abacavir/Lamivudine- 60/30mg tablets in HIV infected Children
Brief summary describing the background and objectives of the trial A phase I/II, open label, randomized crossover pharmacokinetic, safety and acceptability study of the Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination vs. Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg tablets) in HIV infected Children. The study is intended to support the adoption of the 4-in-1 by healthcare providers and will provide data that may support its registration in certain countries. The study will be carried out in HIV-infected children in Uganda weighing 3 to 25 kg (inclusive) and unable to swallow tablets and will provide supportive clinical data on the pharmacokinetics, safety, tolerability and acceptability of the 4-in-1. The primary objective is to estimate the population average exposure to LPV, ABC and 3TC provided by the 4-in-1 formulation in HIV-infected children dosed per WHO weight bands.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LOLIPOP
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 15/04/2019
Actual trial start date
Anticipated date of last follow up 11/08/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 45
Actual target sample size (number of participants)
Recruitment status Not yet 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 Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification 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 4in1 Arm Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/40/10mg) Fixed-Dose Combination administered twice daily. Dosage according to patient's weight: Between 3 and 5.9kg: 2 capsules twice a day Between 6 and 9.9kg: 3 capsules twice a day Between 10 and 13.9kg: 4 capsules twice a day Between 14 and 19.9kg: 5 capsules twice a day Between 20 and 24.9kg: 6 capsules twice a day At least 3 weeks children between 3-5.9 Kgs will only receive the 4in1 formulation for at least three weeks. Children >5.9 Kgs will be randomized to receive the 4in1 for at least 3 weeks then cross over to receive LPV/r Pellets (40/10 mgs) Plus ABC/3TC (60/30mgs) for at least 3 weeks 45
Control Group LPV R Pellets Plus ABC 3TC Arm Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) Dosage according to patient's weight: LPV/r Pellets: Between 6 and 9.9kg: 3 capsules twice a day Between 10 and 13.9kg: 4 capsules twice a day Between 14 and 19.9kg: 5 capsules twice a day Between 20 and 24.9kg: 6 capsules twice a day ABC/3TC: Between 3 and 5.9kg: 1 tablet twice a day Between 6 and 9.9kg: 1.5 tablets twice a day Between 10 and 13.9kg: 2 tablets twice a day Between 14 and 19.9kg: 2.5 tablets twice a day Between 20 and 24.9kg: 3 tablets twice a day At least 3 weeks Children will be randomized to receive Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks, followed by Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks 45 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Children > 4 weeks old and weighing ≥3 and <25 kg at the time of enrolment • Past or current documentation of a confirmed diagnosis of HIV infection defined as two positive assays from two different samples. The two results may be in any combination of the following:  At any age: HIV-1 DNA PCR positive  Documented past HIV-1 RNA viral load > 1,000 copies/mL plasma  At any age >18 months of age: HIV-1 antibody reactive on two different rapid tests based on national testing algorithm • ARV treatment eligible children with LPV-based treatment indication as defined by country-specific guidelines or the WHO paediatric treatment guidelines and confirmed by the investigator • HIV RNA viral load <1000 copies/mL (suppressed) at the screening visit* • Inability to swallow LPV/r tablets • Parent or guardian able and willing to provide written informed consent. • For lowest weight band (≥3 and ≤ 5.9kgs) ONLY: under treatment for at least 3 weeks but not more than 12 weeks. *Does not apply to the youngest children (≥3 and ≤ 5.9kgs) • Planned or concurrent use of NNRTIs, integrase inhibitors, entry inhibitors, or Protease Inhibitors (PIs) other than LPV/r. • Treatment failure with proven resistances to PIs. • Contraindication to use of PIs • Clinical condition requiring the use of a prohibited medication (see section 7.6) in association with LPV/r, ABC/3TC (Refer to section 7.2- 7.3 of the IB) • Pulmonary Tuberculosis and any clinically significant disease or finding during screening that, in the investigator’s opinion, would compromise participation in this study. • Treatment with experimental drugs (except for LPV/r Pellets) for any indication within 30 days prior to study entry • Anticipated transfer of care to a non-participating health facility during the study period Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 4 Week(s) 12 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
Yes 26/10/2018 Joint Clinical Research Centre Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa, off Entebbe Road Kampala 00000 Uganda
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 19/12/2018 Institutional Review Board for Baylor College of Medicine and Associated Hospitals
Ethics Committee Address
Street address City Postal code Country
One Baylor Plaza, 600D Houston, Texas 77030 Houston 77030 United States of America
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 18/12/2018 Institutional Review Board Institute of Tropical Medicine Antwerp
Ethics Committee Address
Street address City Postal code Country
Nationalestraat 155, 2000 Antwerp 2000 Belgium
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • LPV, ABC and 3TC AUC0-12 in the 4-in-1 formulation. Day 22 and Day 43
Secondary Outcome Pharmacokinetics: • LPV C12 with the 4-in-1 formulation. • LPV, ABC and 3TC Cmax, Tmax, CL/F with the 4-in-1 formulation. • Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC AUC0-12 and Cmax in the 4-in-1 formulation versus the reference treatment regimen. Safety, Tolerability: • Occurrence of (treatment-emergent) adverse events (TEAEs) as defined by the protocol • Occurrence of severe treatment-emergent adverse events (TEAEs) as defined by the protocol • Occurrence of treatment-emergent AE (TEAEs) /serious TEAE leading to treatment discontinuation • Occurrence of targeted TEAEs for lopinavir/ritonavir as well as NRTIs (examples: gastrointestinal side effects, liver toxicity, ABC-associated hypersensitivity reaction) • Proportion of children with viral load <1000 copies/ml • Changes in CD4 counts and percent compared to baseline Acceptability: • Factors that affect acceptability of the 4 in1 formulation will be identified by means of a questionnaire and in-depth interviews Day 22 and Day 43
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Joint Clinical Research Centre Plot 101 Lubowa Estate off Entebbe Road Kampala Uganda
Baylor College of Medicine Childrens Foundation Uganda Bolck 5 Mulago Hospital Kampala Uganda
Epicentre Mbarara P.O.Box 1956, Mbarara Mbarara Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
UNITAID Chemin du Pommier 40, 5th floor, 1218 Grand-Saconnex Geneva, Switzerland Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Drugs for Neglected Diseases initiative Chemin Louis Dunant 15, 1202 Geneva Geneva Switzerland Not for Profit Research and Development
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Victor Musiime musiimev@yahoo.co.uk +256417723000 Plot 101 Lubowa Estate off Entebbe Road
City Postal code Country Position/Affiliation
Kampala Uganda Joint Clinical Research Centre
Role Name Email Phone Street address
Public Enquiries Moses Waweru mwaweru@dndi.org +254731006798 Tetezi Towers, George padmore road, Kilimani
City Postal code Country Position/Affiliation
Nairobi Kenya Clinical Trial Manager DNDI
Role Name Email Phone Street address
Scientific Enquiries Isabelle Andrieux Meyer iandrieux-meyer@dndi.org +41229069268 15 chemin Louis Dunant
City Postal code Country Position/Affiliation
Geneva Switzerland Head of Clinical Development Paediatric HIV HCV Programs DNDI
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes DNDi will publish its studies, whether results are positive or negative, in open-access peer-reviewed journals. Data will be shared upon publication of study results, in line with the procedures of major medical journals including Nature, PLOS, BMJ, etc Study Protocol Before data collection, clinical trials sponsored by DNDi are registered on public databases. Before data collection, DNDi will also publish on its global website (dndi.org) the synopsis of clinical trial protocols DNDi will post key results of the research 12 months after completion of the trial. Prior to publication and after study completion, data sharing will be available on a request basis for research projects, based on a final and cleaned database. Requests for access will be examined by DNDi’s Scientific Advisory Committee. The scientific justification of the request, compliance by the requesting party with ethical considerations, and a commitment from the requesting party to share with DNDi and publish the results of the follow-on research. In addition, the applicant will commit to acknowledge the source of data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.dndi.org 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