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

Primary Purpose

Schistosomiasis

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Biltricide (racemate praziquantel) oral tablets
Racemate Praziquantel ODT
Levo Praziquantel ODT
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schistosomiasis focused on measuring Praziquantel ODT formulation, Biltricide

Eligibility Criteria

3 Months - 6 Years (Child)All SexesDoes not accept 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

Sites / Locations

  • Please Contact the Communication Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

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

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

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

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

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

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

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

Arm 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.

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

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.

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

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 16, 2016
Last Updated
October 30, 2019
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT02806232
Brief Title
An Open Label Dose Finding Safety and Efficacy in Children and Infants Infected With Schistosomiasis (S.Mansoni)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
June 12, 2016 (Actual)
Primary Completion Date
October 30, 2018 (Actual)
Study Completion Date
November 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schistosomiasis
Keywords
Praziquantel ODT formulation, Biltricide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
444 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1, Cohort 1: Biltricide (racemate praziquantel) 20 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 1, Cohort 2: Biltricide (racemate praziquantel) 40 mg/kg
Arm Type
Experimental
Arm Description
Participants received Biltricide (600 mg tablet) administered orally at a dose of 40 mg/kg as a single dose on treatment Day 1.
Arm Title
Part 1, Cohort 3: Racemate Praziquantel 40 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 1, Cohort 4: Racemate Praziquantel 60 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 1, Cohort 5: Levo Praziquantel 30 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 1, Cohort 6: Levo Praziquantel 45 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 1, Cohort 7: Levo Praziquantel 60 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 2, Cohort 8: Levo Praziquantel 50 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Part 2, Cohort 9: Levo Praziquantel 50 mg/kg
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Biltricide (racemate praziquantel) oral tablets
Intervention Description
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
Intervention Name(s)
Racemate Praziquantel ODT
Intervention Description
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
Intervention Name(s)
Levo Praziquantel ODT
Intervention Description
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 Outcome Measure Information:
Title
Number of Participants With Clinical Cure Determined by Kato-Katz Method
Description
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.
Time Frame
14-21 days post treatment
Secondary Outcome Measure Information:
Title
Egg Reduction Rate (Percent)
Description
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.
Time Frame
Baseline, 14-21 days post treatment
Title
Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test
Description
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.
Time Frame
Day 2, Day 8 and 14-21 days post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Please Contact the Communication Center
City
Darmstadt
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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