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

NCT ID: NCT02806232

Last Updated: 2019-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 444 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-12
• Study Completion Date: 2018-11-17

Brief 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.

Conditions

Schistosomiasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1, Cohort 1: Biltricide (racemate praziquantel) 20 mg/kg

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.

Group Type: EXPERIMENTAL

Biltricide (racemate praziquantel) oral tablets

Intervention Type: 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.

Part 1, Cohort 2: Biltricide (racemate praziquantel) 40 mg/kg

Participants received Biltricide (600 mg tablet) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.

Group Type: EXPERIMENTAL

Biltricide (racemate praziquantel) oral tablets

Intervention Type: 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.

Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg

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.

Group Type: EXPERIMENTAL

Racemate Praziquantel ODT

Intervention Type: 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.

Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg

Participants received Racemate Praziquantel ODT (150 mg) administered orally at a dose of 60 mg/kg as a single dose on treatment Day 1.

Group Type: EXPERIMENTAL

Racemate Praziquantel ODT

Intervention Type: 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.

Part 1, Cohort 5: Levo Praziquantel 30 mg/kg

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.

Group Type: EXPERIMENTAL

Levo Praziquantel ODT

Intervention Type: 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.

Part 1, Cohort 6: Levo Praziquantel 45 mg/kg

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.

Group Type: EXPERIMENTAL

Levo Praziquantel ODT

Intervention Type: 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.

Part 1, Cohort 7: Levo Praziquantel 60 mg/kg

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.

Group Type: EXPERIMENTAL

Levo Praziquantel ODT

Intervention Type: 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.

Part 2, Cohort 8: Levo Praziquantel 50 mg/kg

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.

Group Type: EXPERIMENTAL

Levo Praziquantel ODT

Intervention Type: 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.

Part 2, Cohort 9: Levo Praziquantel 50 mg/kg

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.

Group Type: EXPERIMENTAL

Levo Praziquantel ODT

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Please Contact the Communication Center

Darmstadt, , Germany

Countries

Germany

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

200661-0005

Identifier Type: -

Identifier Source: org_study_id