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.: PACTR201810634034543 Date of Approval: 30/10/2018
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Phase III pediatric study with the L-PZQ ODTs
Official scientific title Open-label, Phase 3 efficacy and safety study of L-praziquantel orodispersible tablets (L-PZQ ODT) in Schistosoma-infected children 3 months to 6 years of age, including a 2:1 randomized, controlled cohort of Schistosoma mansoni-infected children 4 to 6 years of age treated with L-PZQ ODT or commercial PZQ (Biltricide®).
Brief summary describing the background and objectives of the trial This is a Phase 3 safety/efficacy study in Schistosoma-infected African children 3 months to 6 years of age and it is part of the PZQ ODT clinical development program, which aims to register a single dose of the new ODTs in the targeted pediatric age group (3 months to 6 years of age). The rationale for this study is based on data gathered from previously conducted Phase 1 and Phase 2 clinical studies with the new PZQ ODTs.
Type of trial RCT
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 S. mansoni and S. haematobium
Purpose of the trial Treatment: Drugs
Anticipated trial start date 20/05/2019
Actual trial start date 02/09/2020
Anticipated date of last follow up 07/08/2021
Actual Last follow-up date 07/08/2021
Anticipated target sample size (number of participants) 311
Actual target sample size (number of participants) 288
Recruitment status Completed
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program 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 L PZQ ODT L-PZQ ODT at 50 mg/Kg Single dose Single dose of L-PZQ ODT, dispersed in water, after food intake. 100
Control Group Biltricide Biltricide® at 40 mg/Kg Single dose The Biltricide® tablets will be divided into 150-mg parts, crushed, suspended in water, and administered after food intake. 50 Active-Treatment of Control Group
Experimental Group L PZQ ODT L PZQ ODT 50 mg/Kg Single dose Single dose of L-PZQ ODT, dispersed in water, after food intake 41
Experimental Group L PZQ ODT L-PZQ ODT at 50 mg/Kg For Cohort 4, the dose might be increased to 60 mg/Kg after IDMC review Single dose Single dose of L-PZQ ODT, dispersed in water, after food intake 90
Experimental Group L PZQ ODT L PZQ ODT at 50 mg/kg Single dose Single dose 30
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. • 4 to 6 years of age (Cohorts 1 and 4) • 2 to 3 years of age (Cohorts 2 and 4) • 3 to 24 months of age (Cohorts 3 and 4) 2. S. mansoni-positive (Cohorts 1, 2, and 3); diagnosis defined as positive egg counts in stool ≥1 egg/1 occasion) according to WHO classification [1]: light (1 to 99 eggs per gram of feces), moderate (100 to 399 eggs per gram of feces) and heavy (≥400 eggs per gram of feces) infections. • S. haematobium-positive (Cohort 4); diagnosis defined as positive egg counts in urine (≥1 egg/10 mL urine) according to WHO classification 8 : light (<50 eggs/10 mL of urine) and heavy (≥50 eggs/10 mL of urine) infections 3. Have a minimum body weight of 8.0 Kg in 2 to 6 years of age children and 5.0 Kg in 3 months to 24 months of age infants and toddlers. 4. Are male or female. 5. Parent or guardian/legally authorized representative can give signed informed consent, as indicated in Appendix 2 (Study Governance), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol. 6. Parent’s or guardian/legally authorized representative’s ability to communicate well with the Investigator and his/her delegate, to understand the protocol requirements and restrictions, and to be willing to have their children comply with the requirements of the entire trial, i.e.: • To be examined by a study physician at screening and 17 to 21 days after treatment • To provide stool samples at screening and 17 to 21 days after treatment • To provide urine samples at screening and 17 to 21 days after treatment • To provide venous blood samples for laboratory assessments • To be housed in the clinic for 12 to 24 hours • To provide venous blood samples for PK assessments (for participants in the PK subset). Additional inclusion criteria for PK sub study participants (see section 8.5 for number of participants and cohort allocation) 7. Have a minimum hemoglobin level of 10 g/dl. 1. Findings in the clinical examination and/or laboratory safety examination on the treatment day, that in the opinion of the Investigator constitute a risk or a contraindication for the child’s participation in the study or that could interfere with the study objectives, conduct or evaluation. This includes but is not restricted to bacterial or viral infections, such as dysentery, gastroenteritis, ascites, jaundice, etc. 2. Participants with seizures and/or medical history of seizures and/or other signs of potential central nervous system involvement. 3. Participants with known cysticercosis, or with signs or symptoms suggestive of cysticercosis. 4. Participants with an acute infection or other acute illness within the 7 days prior to study screening. 5. Debilitating illness such as tuberculosis, malnutrition, etc. 6. Treatment with PZQ within the 4 weeks prior to the study screening. 7. Concomitant treatment (within 2 weeks prior to enrolment) with medication that might affect the metabolism of PZQ, such as certain anti-epileptics, glucocorticosteroids chloroquine, rifampicin or cimetidine 8. Treatment within the 2 weeks prior to the study screening with anti-malarial medications. 9. For infants and toddlers being breast-fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to PZQ ODT administration. 10. Participation in any clinical study within 4 weeks prior to administration of PZQ ODT, or anticipated at any time until completion of the end-of-study visit. 11. Marked increases of the liver enzymes: alanine aminotransferase and/or aspartate aminotransferase above 3 times the upper limit of normal (ULN); total bilirubin level above 1.5 times the ULN. 12. Participants with hepatosplenic schistosomiasis. 13. Fever, defined as temperature above 37.5 °C axillary or oral. 14. Mixed S. haematobium and S. mansoni infections. 15. History of hypersensitivity to PZQ or any of the excipients. Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 3 Month(s) 6 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 09/05/2019 Ethikkommission Nordwest und Zentralschweiz
Ethics Committee Address
Street address City Postal code Country
Hebelstrasse 53 Basel 4056 Switzerland
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 19/03/2019 KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT
Ethics Committee Address
Street address City Postal code Country
P.O. BOX 54840 00200 OFF MBAGATHI ROAD Nairobi 00200 Kenya
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 05/06/2019 Comite National Ethique des Sciences de la Vie et de la Sante CNESVS
Ethics Committee Address
Street address City Postal code Country
BPV 4 Abidjan 4056 Cote Divoire
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To assess the efficacy of a single dose (50 mg/Kg) of L-PZQ ODT as assessed by cure rate 17 to 21 days after treatment, in children 4 to 6 years of age infected with S. mansoni (Treatment group 1a). The efficacy of a single dose (40 mg/Kg) of commercial PZQ tablets (Biltricide®) in the same patient population (Treatment group 1b) will be considered as an internal control. Clinical cure is defined as no parasite eggs in the stool 17 to 21 days after treatment.
Secondary Outcome To assess the safety of a single dose (50 mg/Kg) of L- PZQ ODT in children 4 to 6 years of age infected with S. mansoni (Treatment group 1a). Safety and tolerability assessments
Secondary Outcome To assess the efficacy of a single dose (50 mg/Kg) of L-PZQ ODT as assessed by cure rate 17 to 21 days after treatment, in children 2 to 3 years of age and in infants/toddlers 3 to 24 months of age infected with S. mansoni (Cohorts 2 and 3, respectively) Same as Cohort 1.
Secondary Outcome To assess the safety of a single dose (50 mg/Kg) of L-PZQ ODT in children 2 to 3 years of age and in infants/toddlers 3 months to 24 months of age infected with S. mansoni (Cohort 2 and 3, respectively) Same as Cohort 1.
Secondary Outcome To assess the efficacy of a single dose (50 mg/Kg) of L-PZQ ODT as assessed by cure rate 17 to 21 days after treatment, in children 3 months to 6 years of age infected with S. haematobium (Cohort 4). Clinical cure is defined as no parasite eggs in the urine 17 to 21 days after treatment.
Secondary Outcome To assess the safety of a single dose (50 mg/Kg) of L-PZQ ODT in children 3 months to 6 years of age infected with S. haematobium (Cohort 4) Same as Cohort 1.
Secondary Outcome To assess the efficacy of a single dose (50 mg/Kg) of the L-PZQ ODT as assessed by egg reduction rate (ERR) 17 to 21 days after treatment, in children 4 to 6 years of age infected with S. mansoni (Treatment group 1a). The efficacy (ERR) of a single dose (40 mg/Kg) of commercial PZQ tablets (Biltricide®) in the same patient population (Treatment group 1b) will be considered as an internal control. ERR from pre-treatment to 17 to 21 days after treatment, using parasite egg counts as determined by the Kato-Katz method for Cohort 1.
Secondary Outcome To assess the efficacy of a single dose (50 mg/Kg) of L-PZQ ODT as determined by ERR in children 2 to 3 years of age and in infants and toddlers 3 months to 24 months of age infected with S. mansoni (Cohorts 2 and 3, respectively) and in children 3 months to 6 years of age infected with S. haematobium (Cohort 4). ERR from pre-treatment to 17 to 21 days after treatment, using parasite egg counts as determined by the Kato-Katz method for Cohorts 2 and 3 and the urine filtration method for Cohort 4.
Secondary Outcome To assess the cure rate as demonstrated with use of the commercially available point-of-care circulating cathodic antigen (POC-CCA®) test (Cohorts 1, 2, and 3). One urine sample will be collected 17 to 21 days after treatment.
Secondary Outcome To assess acceptability in terms of ease of administration of the selected ODT (Treatment group 1a, Cohorts 2, 3 and 4) and commercial PZQ tablet (Treatment group 1b) Reaction to study intervention administration at study intervention administration.
Secondary Outcome To assess the concentration-time profile of the L-PZQ ODT formulation in a subset of children Concentrations of L-PZQ and, if appropriate, PK parameters, H0 to 12 hours afterwards
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Regional Hospital CHR de Man BP 412 Man Cote Divoire
Homa Bay County Teaching and Referral Hospital P. O. Box 52 Homa Bay 40300 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
The EDCTP Association P.O. Box 93015 2509 AA The Haage Netherlands
The Global Health Innovative Technology Fund Ark Hills Sengokuyama Mori Tower 25F, 1-9-10 Roppongi, Minato-ku Tokyo Japan
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Merck KGaA Frankfurterstr. 250 Darmstadt 64293 Germany Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Merck KGaA Frankfurterstr. 250 Darmstadt 64293 Germany
Astellas Pharma Inc. 5-1 Nihonbashi-Honcho, 2-chome, Chuo-ku Tokyo 1038411 Japan
Swiss Tropical and Public Health Institute Socinstrasse 57 Basel 4051 Switzerland
Farmanguinhos Av. Comandante Guaranys, 447 Jacarepagua Rio de Janeiro Brazil
Schistosomiasis Control Initiative St. Marys Campus, Nofolk Place London United Kingdom
Kenya Medical Research Institute Off Mbagathi Road Nairobi 548400020 Kenya
Universite Felix Houphouet Boigny 01 BP V 43 Abidjan 01 Cote Divoire
Lygature Jaarbeursplein 6 Utrecht 3521 Netherlands
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Merck KGaA Communication Center service@merckgroup.com 00496151725200 Frankfurterstrasse 250
City Postal code Country Position/Affiliation
Darmstadt 64293 Germany Communication Officer
Role Name Email Phone Street address
Scientific Enquiries Elly Kourany Lefoll Elly.Kourany-Lefoll@merckgroup.com 0041219003174 6 Rue de la Verrerie
City Postal code Country Position/Affiliation
Coinsins 1267 Switzerland e TIP Global Health
Role Name Email Phone Street address
Principal Investigator Maurice Odiere mauriceodiere@gmail.com 0025420203071 P. O. Box 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Kenya Medical Research Institute
Role Name Email Phone Street address
Principal Investigator Eliezer Kouakou NGoran eliezerngoran@yahoo.fr +22505076581 22 BP 770
City Postal code Country Position/Affiliation
Abidjan Cote Divoire Professeur de Parasitologie et Ecologie parasitaire
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
No
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