L-PZQ ODT in Schistosoma Infected Children

Study Overview
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Brief Summary
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The study will evaluate the safety and efficacy of L-praziquantel orodispersible (L-PZQ ODT) tablets in Schistosoma infected children aged 3 months to 6 years.

Official Title
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An Open Label, Phase III Efficacy and Safety Study of 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®)

Conditions
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Schistosomiasis

Intervention / Treatment
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* Drug: L-PZQ ODT
* Drug: Biltricide®
* Drug: L-PZQ ODT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of the participant is 4 to 6 years of age (Cohorts 1 and 4), 2 to 3 years of age (Cohorts 2 and 4) 3 to less than 24 months of age (Cohorts 3 and 4) Participants are; Schistosoma (S.) mansoni positive (Cohorts 1, 2, and 3); diagnosis defined as positive egg counts in stool greater than or equal to ( >=) 1 egg per 1 occasion) according to World Health Organization (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 per 10 milliliter(mL) urine) according to WHO classification (Prevention and Control of Schistosomiasis and Soil Transmitted Helminthiasis. WHO Technical Report Series No. 912. WHO, Geneva, Switzerland, 2002).light (less than (<) 50 eggs per 10 mL of urine) and heavy (>=50 eggs per 10 mL of urine) infections Participants have a minimum body weight of 8.0 Kilograms (Kg) in 2 to 6 years of age children and 5.0 Kg in 3 months to < 24 months of age infants and toddlers 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 study, that is: 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 pharmacokinetics (PK) assessments (for participants in the PK subset) Participants have a minimum hemoglobin level of 10 gram per deciliter Exclusion Criteria: Participants with following medical conditions are excluded from the study; 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.; Participants with seizures and/or medical history of seizures and/or other signs of potential central nervous system involvement; Participants with known cysticercosis, or with signs or symptoms (for example: subcutaneous nodules) suggestive of cysticercosis; Participants with an acute infection or other acute illness within the 7 days prior to study screening; Debilitating illness such as tuberculosis, malnutrition, etc. Treatment with PZQ within the 4 weeks prior to the study screening Concomitant treatment (within 2 weeks prior to enrollment) with medication that might affect the metabolism of PZQ, such as certain anti epileptics (for example: carbamazepine or phenytoin), glucocorticosteroids (for example: dexamethasone), chloroquine, rifampicin or cimetidine (see Biltricide® Summary of Product Characteristics [SmPC]) Treatment within the 2 weeks prior to the study screening with anti malarial medications For infants and toddlers being breast fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to PZQ ODT administration 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 Participants with 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 Participants with hepatosplenic schistosomiasis Fever, defined as temperature above 37.5 degree Celsius axillary or oral mixed S. haematobium and S. mansoni infections

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: Cohort 1, Treatment 1a: L-PZQ ODT<br>Participants aged 4 to 6 years infected with Schistosoma (S.) mansoni will receive single oral dose of L-PZQ ODT 50 milligram/Kilogram (mg/Kg) after food-intake. | Drug: L-PZQ ODT<br>* Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.<br>|
| Active Comparator: Cohort 1, Treatment 1b: Biltricide®<br>Participants aged 4 to 6 years infected with S. mansoni will receive single oral dose of Biltricide® 40 mg/Kg crushed tablet after food intake. | Drug: Biltricide®<br>* Participants will receive single oral dose of Biltricide® 40 mg/kg crushed tablet on Day 1.<br>|
| Experimental: Cohort 2: L-PZQ ODT<br>Participants aged 2 to 3 years infected with S. mansoni will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake. | Drug: L-PZQ ODT<br>* Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.<br>|
| Experimental: Cohort 3: L-PZQ ODT<br>Participants aged 3 to less than 24 months infected with S. mansoni will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake. | Drug: L-PZQ ODT<br>* Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.<br>|
| Experimental: Cohort 4: L-PZQ ODT<br>Participants aged 3 months to 6 years infected with S. haematobium will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake. Additional participants will receive 60 mg/Kg of L-PZQ ODT as decided by the Independent data monitoring committee (IDMC). | Drug: L-PZQ ODT<br>* Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.<br>Drug: L-PZQ ODT<br>* Participant will receive single oral dose of L-PZQ ODT 60 mg/kg as decided by the IDMC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of Participants With Clinical Cure | Clinical cure is defined as no parasite eggs in the stool or urine 17 to 21 days post-treatment. | 17 to 21 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Egg Reduction Rate | Egg reduction rate will be calculated using parasite egg counts as determined by the Kato Katz method for Cohorts 1, 2 and 3 and the urine filtration method for Cohort 4. | Pre-treatment, 17 to 21 days post-treatment | 
| Cure Rate | Cure defined as no evidence of parasite antigens in urine as measured with Point-of-Care Circulating Cathodic Antigen (POC-CCA) test. | 17 to 21 days post-treatment | 
| Acceptability of the Study Intervention | Acceptability of the study intervention will be recorded as the reaction of participants to study intervention. The acceptability will be assessed by the nurse/site staff for all children enrolled in the study. | Day 1 | 
| Maximum Observed Plasma Concentration (Cmax) of L-PZQ ODT |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ ODT |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of L-PZQ ODT |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) |  | Day 1 up to Day 21 | 
| Occurrence of Treatment Related Adverse Events |  | Day 1 up to Day 21 | 
| Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Number of participants with clinically significant changes will be reported. | Day 1 up to Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schistosomiasis, Children, L-praziquantel, Biltricide®