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

Schistosomiasis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02806232
• Other study ID #: 200661-0005
• Status: Completed
• Phase: Phase 2
• Start date: June 12, 2016
• Est. completion date: November 17, 2018

Study information

• Verified date: October 2019
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: November 17, 2018
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Schistosomiasis

Intervention

Drug:
• Biltricide (racemate praziquantel) oral tablets
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
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
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.

Locations

Country	Name	City	State
Germany	Please Contact the Communication Center	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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