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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2

Conditions: Schistosomiasis

Treatments: Drug: Biltricide (racemate praziquantel) oral tablets; Drug: Racemate Praziquantel ODT; Drug: Levo Praziquantel ODT

Study type: Interventional

Funder types: Industry

Identifiers

NCT02806232

200661-0005

Details and patient eligibility

About

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.

Enrollment: 444 patients

Sex: All

Ages: 3 months to 6 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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444 participants in 9 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Biltricide (racemate praziquantel) oral tablets

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

Experimental group

Description:

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

Treatment:

Drug: Biltricide (racemate praziquantel) oral tablets

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

Experimental group

Description:

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.

Treatment:

Drug: Racemate Praziquantel ODT

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

Experimental group

Description:

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

Treatment:

Drug: Racemate Praziquantel ODT

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

Experimental group

Description:

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.

Treatment:

Drug: Levo Praziquantel ODT

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

Experimental group

Description:

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.

Treatment:

Drug: Levo Praziquantel ODT

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

Experimental group

Description:

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.

Treatment:

Drug: Levo Praziquantel ODT

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

Experimental group

Description:

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.

Treatment:

Drug: Levo Praziquantel ODT

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

Experimental group

Description:

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.

Treatment:

Drug: Levo Praziquantel ODT