An Open Label Dose Finding Safety and Efficacy in Children and Infants Infected With Schistosomiasis (S.Mansoni)

Study Overview
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Brief Summary
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The Phase II study consisted of two parts, part 1 is open label, randomized, controlled and exploratory dose finding in children aged between 2 and 6 years infected with S. mansoni. Part 2 investigated efficacy and safety with the selected formulation and dosage in S. mansoni infected children aged between 3 months - 2 years.

Official Title
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Open-label, Dose-finding, 2-parts, Efficacy Phase II Study With Three Formulations (Racemate Raziquantel Commercial Oral Tablets, New Oral Disintegrating Tablets of Racemate Praziquantel and L-praziquantel) in Schistosomiasis (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 2)

Conditions
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Schistosomiasis

Intervention / Treatment
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* Drug: Biltricide (racemate praziquantel) oral tablets
* Drug: Racemate Praziquantel ODT
* Drug: Levo Praziquantel ODT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children aged 2 to 6 years (Part 1) and 3 to 24 months (Part 2) S. mansoni positive diagnosis defined as positive egg counts in stool (greater than [>]1 egg/1 occasion) according to World Health Organization (WHO) classification : light (1-99 eggs per gram of faeces), moderate (100-399 eggs per gram of faeces) and heavy (greater than or equal to [>=]400 eggs per gram of faeces) 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 representative 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 hours and 8 days after treatment, as well as 14-21 days after treatment To provide finger prick blood samples for Pharmacokinetics (PK) studies and blood samples for safety assessments Exclusion Criteria: Treatment in the 4 weeks prior to study screening with Praziquantel (PZQ) , other anti-helminthic, antimalarial 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 Investigational medicinal product Previous history of adverse reactions associated with PZQ treatment Marked increases of the liver transaminases (alanine aminotransferase and/or aspartate aminotransferase) above 3x Upper Limit of Normal (ULN) History of acute or severe chronic disease including hepato-splenic schistosomiasis Fever defined as temperature above 38.0 degree centigrade Debilitating illnesses such as tuberculosis, malnutrition, etc. as well as a medical history of seizures 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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1, Cohort 1: Biltricide (racemate praziquantel) 20 mg/kg<br>Participants received Biltricide (600 mg tablet) administered orally at a dose of 20 milligram per kilogram (mg/kg), three times a day on treatment Day 1. | Drug: Biltricide (racemate praziquantel) oral tablets<br>* Biltricide (600 mg tablet) was administered to participants at a dose of 20 mg/kg in Part 1, Cohort 1 and at a dose of 40mg/kg in Part 1, Cohort 2.<br>|
| Experimental: Part 1, Cohort 2: Biltricide (racemate praziquantel) 40 mg/kg<br>Participants received Biltricide (600 mg tablet) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1. | Drug: Biltricide (racemate praziquantel) oral tablets<br>* Biltricide (600 mg tablet) was administered to participants at a dose of 20 mg/kg in Part 1, Cohort 1 and at a dose of 40mg/kg in Part 1, Cohort 2.<br>|
| Experimental: Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg<br>Participants received Racemate Praziquantel oral dispersible tablet (ODT) (150 mg) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1. | Drug: Racemate Praziquantel ODT<br>* Racemate Praziquantel (PZQ) (150) mg was administered at a dose of 40 mg/kg in Part 1, Cohort 3 and at a dose of 60 mg/kg in Part 1, Cohort 4.<br>|
| Experimental: Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg<br>Participants received Racemate Praziquantel ODT (150 mg) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1. | Drug: Racemate Praziquantel ODT<br>* Racemate Praziquantel (PZQ) (150) mg was administered at a dose of 40 mg/kg in Part 1, Cohort 3 and at a dose of 60 mg/kg in Part 1, Cohort 4.<br>|
| Experimental: Part 1, Cohort 5: Levo Praziquantel 30 mg/kg<br>Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 30 mg/kg as a single dose on treatment Day 1. | Drug: Levo Praziquantel ODT<br>* Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.<br>|
| Experimental: Part 1, Cohort 6: Levo Praziquantel 45 mg/kg<br>Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 45 mg/kg as a single dose on treatment Day 1. | Drug: Levo Praziquantel ODT<br>* Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.<br>|
| Experimental: Part 1, Cohort 7: Levo Praziquantel 60 mg/kg<br>Participants received Levo Praziquantel ODT (150 mg tablet) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1. | Drug: Levo Praziquantel ODT<br>* Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.<br>|
| Experimental: Part 2, Cohort 8: Levo Praziquantel 50 mg/kg<br>Participants aged 13-24 months months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1. | Drug: Levo Praziquantel ODT<br>* Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.<br>|
| Experimental: Part 2, Cohort 9: Levo Praziquantel 50 mg/kg<br>Participants aged 3 to 12 months received Levo Praziquantel ODT (150 mg) administered orally at a dose of 50 mg/kg as a single dose on treatment day 1. | Drug: Levo Praziquantel ODT<br>* Levo PZQ (150 mg) was administered at a dose of 30 mg/kg in Part 1 Cohort 5, 45 mg/kg Part 1 Cohort 6, 60 mg/kg Part 1 Cohort 7, 50 mg/kg Part 2 Cohort 8, and 50 mg/kg Part 2 Cohort 9.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Cure Determined by Kato-Katz Method | Clinical cure was defined as zero egg counts at 14-21 days post treatment as determined by the Kato-Katz method. Number of participants with clinical cure were reported. | 14-21 days post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Egg Reduction Rate (Percent) | Percent reduction in egg count was calculated as geometric mean egg count at post-treatment minus geometric mean egg count at baseline (before treatment) divided by geometric mean egg count at baseline. | Baseline, 14-21 days post treatment | 
| Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test | Clinical Cure defined as no parasite eggs in the stools as assessed by the commercially available POC-CCA assay for S. mansoni. Number of participants with clinical cure were reported. | Day 2, Day 8 and 14-21 days post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Praziquantel ODT formulation, Biltricide