L-PZQ ODT in Schistosoma Infected Children

NCT03845140 | Completed Phase 3 Results DMC

• 1 other identifier: MS200661_0003
• Study Type: interventional
• Target: 288
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Schistosomiasis

Keywords

Schistosomiasis; Children; L-praziquantel; Biltricide®

Outcome Measures

Primary Outcomes (1)

• Cohort 1a and Cohort 1b: Number of Participants With Clinical Cure Determined by Kato-Katz Method

  Clinical cure was defined as no parasite egg in the stool at Week 3 as determined by the Kato-Katz method. Number of participants with clinical cure were reported.

  at Week 3

Secondary Outcomes (30)

• Cohort 2 and Cohort 3: Number of Participants With Clinical Cure Determined by Kato-Katz Method

  at Week 3

• Cohort 4a and Cohort 4b: Number of Participants With Clinical Cure Determined by Urine Filtration Technique

  Week 3 and Week 5

• Cohort 1a, Cohort 1b, Cohort 2 and Cohort 3: Egg Reduction Rate (Percent [%]) Determined by Kato-Katz Method

  Pre-treatment, Week 3 post-treatment

• Cohort 4a and Cohort 4b: Egg Reduction Rate (Percent [%]) Determined by Urine Filtration Technique

  Pre-treatment, Weeks 3 and 5 post-treatment

• Cohort 1a, Cohort 1b, Cohort 2, and Cohort 3: Number of Participants With Clinical Cure Determined by Point-of-Care Circulating Cathodic Antigen (POC-CCA) Test

  at Week 3

Study Arms (6)

Cohort 1a: 4 to 6 years L-PZQ ODT 50 mg/kg

EXPERIMENTAL

Participants aged 4 to 6 years infected with Schistosoma (S.) mansoni received Levorotatory enantiomer of praziquantel (L-PZQ) orodispersible tablets (ODT) (150 milligrams \[mg\]) orally at a dose of 50 milligram per kilogram (mg/Kg) as a single oral dose after food-intake on Day 1.

Drug: L-PZQ ODT 50 mg/kg

Cohort 1b: 4 to 6 years Biltricide® 40 mg/kg

ACTIVE COMPARATOR

Participants aged 4 to 6 years infected with S. mansoni received Racemate Praziquantel tablets (Biltricide®) (600 mg) orally at a dose of 40 mg/kg as a single oral dose after food-intake on Day 1.

Drug: Biltricide®

Cohort 2: 2 to 3 years L-PZQ ODT 50 mg/kg

EXPERIMENTAL

Participants aged 2 to 3 years infected with S. mansoni received L-PZQ ODT (150 mg) tablet orally at a dose of 50 mg/kg as a single oral dose after food-intake on Day 1.

Drug: L-PZQ ODT 50 mg/kg

Cohort 3: 3 to 24 months L-PZQ ODT 50 mg/kg

EXPERIMENTAL

Participants aged 3 to 24 months infected with S. mansoni received L-PZQ ODT (150 mg) tablet orally at a dose of 50 mg/kg as a single oral dose after food-intake on Day 1.

Drug: L-PZQ ODT 50 mg/kg

Cohort 4a: 3 months to 6 years L-PZQ ODT 50 mg/kg

EXPERIMENTAL

Participants aged 3 months to 6 years infected with S. haematobium received L-PZQ ODT (150 mg) tablet orally at a dose of 50 mg/kg as a single oral dose after food-intake on Day 1.

Drug: L-PZQ ODT 50 mg/kg

Cohort 4b: 3 months to 6 years L-PZQ ODT 60 mg/kg

EXPERIMENTAL

Participants aged 3 months to 6 years infected with S. haematobium received L-PZQ ODT (150 mg) tablet orally at a dose of 60 mg/kg as a single oral dose after food-intake on Day 1.

Drug: L-PZQ ODT 60 mg/kg

Interventions

L-PZQ ODT 50 mg/kg DRUG

Participants received single oral dose of L-PZQ ODT 50 mg/Kg on Day 1.

Cohort 1a: 4 to 6 years L-PZQ ODT 50 mg/kg; Cohort 2: 2 to 3 years L-PZQ ODT 50 mg/kg; Cohort 3: 3 to 24 months L-PZQ ODT 50 mg/kg; Cohort 4a: 3 months to 6 years L-PZQ ODT 50 mg/kg

Biltricide® DRUG

Participants received single oral dose of Biltricide® 40 mg/kg on Day 1.

Cohort 1b: 4 to 6 years Biltricide® 40 mg/kg

L-PZQ ODT 60 mg/kg DRUG

Participant received single oral dose of L-PZQ ODT 60 mg/kg on Day 1.

Cohort 4b: 3 months to 6 years L-PZQ ODT 60 mg/kg

Eligibility Criteria

• Age: 3 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (2)

Universitè de Cocody

Abidjan, 22BP770, Côte d’Ivoire

Location

Kemri Kisumu

Kisumu, 40100, Kenya

Location

Related Publications (1)

• N'Goran EK, Odiere MR, Assande Aka R, Ouattara M, Aka NAD, Ogutu B, Rawago F, Bagchus WM, Bodding M, Kourany-Lefoll E, Tappert A, Yin X, Bezuidenhout D, Badenhorst H, Huber E, Dalken B, Haj-Ali Saflo O. Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Cote d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial. Lancet Infect Dis. 2023 Jul;23(7):867-876. doi: 10.1016/S1473-3099(23)00048-8. Epub 2023 Mar 6.

  PMID: 36893784 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Schistosomiasis

Interventions

Praziquantel

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 19, 2019
• Study Start: September 2, 2019
• Primary Completion: October 11, 2021
• Study Completion: October 11, 2021
• Last Updated: March 21, 2024
• Results First Posted: March 21, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.

Locations

KE (1); CÔ (1)