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

• Biltricide (racemate praziquantel) oral tablets (Drug): 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.
• Racemate Praziquantel ODT (Drug): 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.
• Levo Praziquantel ODT (Drug): 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.

Primary outcomes

• Number of Participants With Clinical Cure Determined by Kato-Katz Method [14-21 days post treatment]: 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.

Secondary outcomes

• Egg Reduction Rate (Percent) [Baseline, 14-21 days post treatment]: 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.
• Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test [Day 2, Day 8 and 14-21 days post treatment]: 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.

Sex: All, ages: 3 Months to 6 Years

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

Participant flow

Outcome results

• Number of Participants With Clinical Cure Determined by Kato-Katz Method (Primary), Count of participants, Participants: Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg 51; Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg 43; Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg 47; Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg 46; Part 1, Cohort 5: Levo Praziquantel 30 mg/kg 44; Part 1, Cohort 6: Levo Praziquantel 45 mg/kg 49; Part 1, Cohort 7: Levo Praziquantel 60 mg/kg 52; Part 2, Cohort 8: Levo Praziquantel 50 mg/kg 14; Part 2, Cohort 9: Levo Praziquantel 50 mg/kg 4
• Egg Reduction Rate (Percent) (Secondary), Geometric mean, percent reduction in egg count: Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg 94.6 (89.8 to 99.4); Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg 83.3 (74.7 to 91.9); Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg 88.6 (81.8 to 95.4); Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg 88.6 (82.2 to 94.9); Part 1, Cohort 5: Levo Praziquantel 30 mg/kg 88.3 (81.3 to 95.3); Part 1, Cohort 6: Levo Praziquantel 45 mg/kg 92.3 (86.4 to 98.1); Part 1, Cohort 7: Levo Praziquantel 60 mg/kg 94.1 (88.6 to 99.6); Part 2, Cohort 8: Levo Praziquantel 50 mg/kg 97.7 (92.9 to 100.0); Part 2, Cohort 9: Levo Praziquantel 50 mg/kg 100.0 (100.0 to 100.0)
• Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test (Secondary), Count of participants, Participants: Part 1, Cohort 1: Biltricide (Racemate Praziquantel) 20 mg/kg 8; Part 1, Cohort 2: Biltricide (Racemate Praziquantel) 40 mg/kg 3; Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg 3; Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg 8; Part 1, Cohort 5: Levo Praziquantel 30 mg/kg 4; Part 1, Cohort 6: Levo Praziquantel 45 mg/kg 6; Part 1, Cohort 7: Levo Praziquantel 60 mg/kg 11; Part 2, Cohort 8: Levo Praziquantel 50 mg/kg 5; Part 2, Cohort 9: Levo Praziquantel 50 mg/kg 0

Adverse events

Time frame: Day 1 to Day 21

Serious adverse events by term

Other adverse events by term

• Statistical Analysis Plan (PDF, 2018-01-31)
• Study Protocol (PDF, 2018-02-28)

• Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany