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.: PACTR201604001493593 Date of Approval: 25/02/2016
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Phase II pediatric dose-finding study with rac-PZQ and L-PZQ ODTs
Official scientific title Open-label, dose-finding, 2-parts, efficacy phase II study with 3 formulations (rac-PZQ commercial oral tablets, new ODTs of rac- and L-PZQ) in S. mansoni infected children aged 2 6 years (Part 1), followed by an assessment of efficacy and safety with the selected formulation and dosage in S. mansoni infected infants aged 3-24 months (Part 2a) and in S. haematobium infected children aged 2-6 years
Brief summary describing the background and objectives of the trial Schistosomiasis, also called bilharzia, belongs to one of the most neglected tropical diseases caused by flatworms and remains one of the most prevalent parasitic diseases in developing countries. The prevalence of schistosomiasis in children is very high, accounting for about 50% of the total infected population of 220 million and many more are at risk from the disease. Pre-school aged children which are a high-risk group for schistosome infections accounting for 10-20 million of the global prevalence are currently not included in the schistosomiasis control programs due to the lack of a suitable PZQ pediatric formulation. The ultimate goal of this phase II study is to identify the optimal dose of a water-dispersible PZQ formulation (either L-PZQ or rac-PZQ) for further confirmation of safety and efficacy in a phase III trial in pre-school aged children infected with S. mansoni. First, the optimal ODT dose (dose that delivers a clinically meaningful efficacy with an acceptable safety profile) to treat children aged 2-6 years infected with S. mansoni will be identified. Younger children (13 to 24 months) infected with S. mansoni will subsequently be treated with the selected ODT dose from Part 1 corrected due to allometric scaling of PK data as well as a maturation factor (to compensate for the immature metabolic system in infants). Only when this corrected dose has been assessed as safe, lower aged children 3 to 12 months will be included.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Paediatrics
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 23/05/2016
Actual trial start date
Anticipated date of last follow up 05/05/2017
Actual Last follow-up date
Anticipated target sample size (number of participants) 520
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
MS200661-0005 Merck KGaA
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 stratified allocation by infection intensity Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group commercial rac-PZQ tablets (Biltricide®) 20 mg/kg dose t.i.d. 1 day 2-6 years old children infected with S. mansoni. The tablets (scored) will be divided into 150 mg parts, crushed, suspended in water and the solution will be swallowed after a meal. 60 Active-Treatment of Control Group
Control Group commercial rac-PZQ tablets (Biltricide®) 40 mg/kg single dose 2-6 years old children infected with S. mansoni. The tablets (scored) will be divided into 150 mg parts, crushed, suspended in water and the solution will be swallowed after a meal. 60 Active-Treatment of Control Group
Experimental Group Rac-PZQ ODTs 40 mg/kg single dose 2-6 years old children infected with S.mansoni. The tablets (150 mg each) will be dispersed in water and the solution will be swallowed after a meal. 60
Experimental Group Rac-PZQ ODTs 60 mg/kg single dose 2-6 years old children infected with S.mansoni. The tablets (150 mg each) will be dispersed in water and the solution will be swallowed after a meal. 60
Experimental Group L-PZQ ODTs 30 mg/kg single dose 2-6 years old children infected with S.mansoni. The tablets (150 mg each) will be dispersed in water and the solution will be swallowed after a meal. 60
Experimental Group L-PZQ ODTs 45 mg/kg single dose 2-6 years old children infected with S. mansoni. The tablets (scored) will be divided into 150 mg parts, crushed, suspended in water and the solution will be swallowed after a meal. 60
Experimental Group L-PZQ ODTs 60 mg/kg single dose optional 2-6 years old children infected with S.mansoni. The tablets (150 mg each) will be dispersed in water and the solution will be swallowed after a meal. 60
Experimental Group Rac- or L-PZQ ODTs Dose defined in Part 1 and including a dose correction, single dose 13-24 months infants infected with S. mansoni. The tablets (scored) will be divided into 150 mg parts, crushed, suspended in water and the solution will be swallowed after a meal. 30
Experimental Group Rac- or L-PZQ ODTs Dose defined in Part 1 and including a dose correction, single dose 3-12 months infants infected with S. mansoni. The tablets (scored) will be divided into 150 mg parts, crushed, suspended in water and the solution will be swallowed after a meal. 10
Experimental Group L-PZQ ODTs Dose defined in Part 1, single dose 2-6 years old children infected with S. haematobium. Tablets (150 mg each) will be dispersed in water and the solution will be swallowed after a meal. 60
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿ Written informed consent from the parents/legal representatives prior to any trial related procedure ¿ Male and female children aged 2 to 6 years (Part 1 and 2b) and 3 to 24 months (Part 2a) ¿ S. mansoni positive diagnosis in Part 1 and Part 2a, defined as positive egg counts in stool (>1 egg/1 occasion) according to WHO classification: light (1-99 eggs per gram of faeces), moderate (100-399 eggs per gram of faeces) and heavy (¿400 eggs per gram of faeces) infections ¿ S. haematobium positive diagnosis in Part 2b, defined as positive egg counts in urine (>2 eggs/10 ml urine) according to WHO classification: light (<50 eggs/10¿ml of urine) and heavy (¿50 eggs/10¿ml of urine) infections ¿ Minimum weight of 8.0 kg in 2- to 6-year-old children and of 4.0 kg in 3- to 24-month infants ¿ Parents/legal guardian¿s ability to communicate well with the Investigator, to understand the protocol requirements and restrictions, and willing their children to comply with the requirements of the entire trial, i.e.: - To be examined by a study physician at screening and 14-21 days after treatment - To provide stool and urine samples at screening, 24 h and 8 days after treatment, as well as 14-21 days after treatment - To provide finger prick blood samples for PK studies and blood samples for safety assessments. ¿ Treatment in the 4 weeks prior to study screening with PZQ, other anti-helminthic, anti-malarial or anti-retroviral compounds or any other medication that might affect the PK of PZQ such as certain antiepileptics (e.g., carbamazepine or phenytoin), glucocorticosteroids (e.g., dexamethasone), chloroquine, rifampicin or cimetidine ¿ For children being breast fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to administration of IMP ¿ Previous history of adverse reactions associated with PZQ treatment ¿ History of acute or severe chronic disease including hepato-splenic schistosomiasis ¿ Fever defined as temperature above 38.0°C ¿ Debilitating illnesses such as tuberculosis, malnutrition, etc. ¿ Mixed S. haematobium and S. mansoni infections ¿ Findings in the clinical examination of schistosome-infected children participating in the study as performed by the study clinician on the treatment day, that in the opinion of the Investigator constitutes a risk or a contraindication for the participation of the subject in the study or that could interfere with the study objectives, conduct or evaluation ¿ Unlikelihood to comply with the protocol requirements, instructions and trial-related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial 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
No Ethics Committee Northwestern/Central Switzerland
Ethics Committee Address
Street address City Postal code Country
Hebelstr. 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
No 03/03/2016 National Committee of Ethics and Research
Ethics Committee Address
Street address City Postal code Country
Abidjan BP V 297 Cote Divoire
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Clinical cure defined as no parasite eggs in the stools (S. mansoni infections) or urine (S. haematobium infections) 14-21 days after treatment. Egg counts will be determined by the Kato-Katz method at screening and 14-21 days after treatment
Secondary Outcome Egg Reduction Rate (ERR, %) calculated based on the arithmetic (and geometric) mean egg count per gram of stool (epg) before and 14-21 days after treatment (as determined by Kato-Katz method). Egg count per gram of stool (epg) will be calculated before and 14-21 days after treatment
Secondary Outcome ¿ Cure defined as no parasite eggs in the stools as assessed by the commercially available POC-CCA test for S. mansoni POC-CCA test will be performed before treatment, 24 hours, 8 days and 14-21 days after treatment
Secondary Outcome Changes in laboratory safety parameters and vital signs (body temperature, blood pressure and pulse rate) Lab safety will be assessed before treatment, 8 hours, 24 hours and 14-21 days after treatment
Secondary Outcome ¿ Occurrence, nature, severity and outcome of adverse events AE will be reported from signature of ICF until end of study visit
Secondary Outcome Occurrence of Adverse Drug Reactions per treatment group Treatment-emergent AEs will also be summarized by relationship to treatment and by severity within each treatment group
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Man Hospital Man Cote Divoire
FUNDING SOURCES
Name of source Street address City Postal code Country
Merck KGaA Frankfurter Strasse 250 Darmstadt 64293 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Merck KGaA Frankfurter Strasse 250 Darmstadt 64293 Germany Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Deon Bezuidenhout 1 Friesland Drive I Longmeadow Business Estate Modderfontein 1645 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Eliézer N'Goran eliezerngoran@yahoo.fr + 225 03 48 88 83
City Postal code Country Position/Affiliation
Abidjan 22 BP 770 Cote Divoire Université Félix Houphouët Boigny
Role Name Email Phone Street address
Public Enquiries Eric Huber eric.huber@unibas.ch +41 (0)61 284 8972 Socinstrasse 57
City Postal code Country Position/Affiliation
Basel 4051 Switzerland Swiss TPH Project Leader
Role Name Email Phone Street address
Scientific Enquiries Wilhelmina Bagchus wilhelmina.bagchus@emdserono.com +1 978-294-1231 45A Middlesex Turnpike
City Postal code Country Position/Affiliation
Billerica MA 01821 United States of America EMD Serono R&D Institute Protocol Lead
REPORTING
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URL Results Available Results Summary Result Posting Date First Journal Publication Date
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Result URL Hyperlinks
Changes to trial information