L-PZQ ODT in Schistosoma Infected Children

• ClinicalTrials.gov Identifier: NCT03845140
• Recruitment Status: Completed
• First Posted: February 19, 2019
• Last Update Posted: October 20, 2021
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Study Description

Brief Summary:

The study will evaluate the safety and efficacy of L-praziquantel orodispersible (L-PZQ ODT) tablets in Schistosoma infected children aged 3 months to 6 years.

Condition or disease	Intervention/treatment	Phase
Schistosomiasis	Drug: L-PZQ ODT; Drug: Biltricide®	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 311 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Phase III Efficacy and Safety Study of L-PZQ ODT in Schistosoma Infected Children 3 Months to 6 Years of Age, Including a 2:1 Randomized, Controlled Cohort of Schistosoma Mansoni Infected Children 4 to 6 Years of Age Treated With L PZQ ODT or Commercial PZQ (Biltricide®)
• Actual Study Start Date: September 2, 2019
• Actual Primary Completion Date: October 11, 2021
• Actual Study Completion Date: October 11, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1, Treatment 1a: L-PZQ ODT; Participants aged 4 to 6 years infected with Schistosoma (S.) mansoni will receive single oral dose of L-PZQ ODT 50 milligram/Kilogram (mg/Kg) after food-intake.	Drug: L-PZQ ODT; Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.
Active Comparator: Cohort 1, Treatment 1b: Biltricide®; Participants aged 4 to 6 years infected with S. mansoni will receive single oral dose of Biltricide® 40 mg/Kg crushed tablet after food intake.	Drug: Biltricide®; Participants will receive single oral dose of Biltricide® 40 mg/kg crushed tablet on Day 1.
Experimental: Cohort 2: L-PZQ ODT; Participants aged 2 to 3 years infected with S. mansoni will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake.	Drug: L-PZQ ODT; Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.
Experimental: Cohort 3: L-PZQ ODT; Participants aged 3 to less than 24 months infected with S. mansoni will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake.	Drug: L-PZQ ODT; Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.
Experimental: Cohort 4: L-PZQ ODT; Participants aged 3 months to 6 years infected with S. haematobium will receive single oral dose of L-PZQ ODT 50 mg/Kg after the food intake. Additional participants will receive 60 mg/Kg of L-PZQ ODT as decided by the Independent data monitoring committee (IDMC).	Drug: L-PZQ ODT; Participants will receive single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.; Drug: L-PZQ ODT; Participant will receive single oral dose of L-PZQ ODT 60 mg/kg as decided by the IDMC.

Outcome Measures

Primary Outcome Measures :

1. Numbers of Participants With Clinical Cure [ Time Frame: 17 to 21 days post-treatment ]
   Clinical cure is defined as no parasite eggs in the stool or urine 17 to 21 days post-treatment.

Secondary Outcome Measures :

1. Egg Reduction Rate [ Time Frame: Pre-treatment, 17 to 21 days post-treatment ]
   Egg reduction rate will be calculated using parasite egg counts as determined by the Kato Katz method for Cohorts 1, 2 and 3 and the urine filtration method for Cohort 4.
2. Cure Rate [ Time Frame: 17 to 21 days post-treatment ]
   Cure defined as no evidence of parasite antigens in urine as measured with Point-of-Care Circulating Cathodic Antigen (POC-CCA) test.
3. Acceptability of the Study Intervention [ Time Frame: Day 1 ]
   Acceptability of the study intervention will be recorded as the reaction of participants to study intervention. The acceptability will be assessed by the nurse/site staff for all children enrolled in the study.
4. Maximum Observed Plasma Concentration (Cmax) of L-PZQ ODT [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
5. Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ ODT [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
6. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of L-PZQ ODT [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose ]
7. Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) [ Time Frame: Day 1 up to Day 21 ]
8. Occurrence of Treatment Related Adverse Events [ Time Frame: Day 1 up to Day 21 ]
9. Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Day 1 up to Day 21 ]
   Number of participants with clinically significant changes will be reported.

Eligibility Criteria

• Ages Eligible for Study: 3 Months to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age of the participant is 4 to 6 years of age (Cohorts 1 and 4), 2 to 3 years of age (Cohorts 2 and 4) 3 to less than 24 months of age (Cohorts 3 and 4)
• Participants are; Schistosoma (S.) mansoni positive (Cohorts 1, 2, and 3); diagnosis defined as positive egg counts in stool greater than or equal to ( >=) 1 egg per 1 occasion) according to World Health Organization (WHO) classification [1]: light (1 to 99 eggs per gram of feces), moderate (100 to 399 eggs per gram of feces) and heavy (>= 400 eggs per gram of feces) infections; S. haematobium positive (Cohort 4); diagnosis defined as positive egg counts in urine (>= 1 egg per 10 milliliter(mL) urine) according to WHO classification (Prevention and Control of Schistosomiasis and Soil Transmitted Helminthiasis. WHO Technical Report Series No. 912. WHO, Geneva, Switzerland, 2002).light (less than (<) 50 eggs per 10 mL of urine) and heavy (>=50 eggs per 10 mL of urine) infections
• Participants have a minimum body weight of 8.0 Kilograms (Kg) in 2 to 6 years of age children and 5.0 Kg in 3 months to < 24 months of age infants and toddlers

• Parent's or guardian/legally authorized representative's ability to communicate well with the Investigator and his/her delegate, to understand the protocol requirements and restrictions, and to be willing to have their children comply with the requirements of the entire study, that is:

  • To be examined by a study physician at screening and 17 to 21 days after treatment
  • To provide stool samples at screening and 17 to 21 days after treatment
  • To provide urine samples at screening and 17 to 21 days after treatment
  • To provide venous blood samples for laboratory assessments
  • To be housed in the clinic for 12 to 24 hours
  • To provide venous blood samples for pharmacokinetics (PK) assessments (for participants in the PK subset)
• Participants have a minimum hemoglobin level of 10 gram per deciliter

Exclusion Criteria:

• Participants with following medical conditions are excluded from the study; Findings in the clinical examination and/or laboratory safety examination on the treatment day, that in the opinion of the Investigator constitute a risk or a contraindication for the child's participation in the study or that could interfere with the study objectives, conduct or evaluation. This includes but is not restricted to bacterial or viral infections, such as dysentery, gastroenteritis, ascites, jaundice, etc.; Participants with seizures and/or medical history of seizures and/or other signs of potential central nervous system involvement; Participants with known cysticercosis, or with signs or symptoms (for example: subcutaneous nodules) suggestive of cysticercosis; Participants with an acute infection or other acute illness within the 7 days prior to study screening; Debilitating illness such as tuberculosis, malnutrition, etc.
• Treatment with PZQ within the 4 weeks prior to the study screening
• Concomitant treatment (within 2 weeks prior to enrollment) with medication that might affect the metabolism of PZQ, such as certain anti epileptics (for example: carbamazepine or phenytoin), glucocorticosteroids (for example: dexamethasone), chloroquine, rifampicin or cimetidine (see Biltricide® Summary of Product Characteristics [SmPC])
• Treatment within the 2 weeks prior to the study screening with anti malarial medications
• For infants and toddlers being breast fed, treatment of the mothers/wet nurses with PZQ in the 3 days prior to PZQ ODT administration
• Participation in any clinical study within 4 weeks prior to administration of PZQ ODT, or anticipated at any time until completion of the End of study visit
• Participants with marked increases of the liver enzymes: alanine aminotransferase and/or aspartate aminotransferase above 3 times the upper limit of normal (ULN); total bilirubin level above 1.5 times the ULN
• Participants with hepatosplenic schistosomiasis
• Fever, defined as temperature above 37.5 degree Celsius axillary or oral mixed S. haematobium and S. mansoni infections

Contacts and Locations

Locations

Côte D'Ivoire

Universitè de Cocody

Abidjan, Côte D'Ivoire, 22BP770

Kenya

Kemri Kisumu

Kisumu, Kenya, 40100

Sponsors and Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

More Information

Additional Information:

Trial Awareness and Transparency website 

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT03845140
• Other Study ID Numbers: MS200661_0003
• First Posted: February 19, 2019
• Last Update Posted: October 20, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• URL: http://bit.ly/IPD21

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck KGaA, Darmstadt, Germany:

Schistosomiasis; Children; L-praziquantel; Biltricide®

Additional relevant MeSH terms:

Schistosomiasis; Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases; Praziquantel; Anthelmintics; Antiparasitic Agents; Anti-Infective Agents