Clinical trial NCT03845140: L-PZQ ODT in Schistosoma Infected Children
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®)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schistosomiasis
Keywords: Schistosomiasis
Children
L-praziquantel
Biltricide®
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 288
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Cohort 1a and Cohort 1b: Number of Participants With Clinical Cure Determined by Kato-Katz Method
timeFrame: at Week 3
Secondary outcomes:
measure: Cohort 2 and Cohort 3: Number of Participants With Clinical Cure Determined by Kato-Katz Method
timeFrame: at Week 3
measure: Cohort 4a and Cohort 4b: Number of Participants With Clinical Cure Determined by Urine Filtration Technique
timeFrame: Week 3 and Week 5
measure: Cohort 1a, Cohort 1b, Cohort 2 and Cohort 3: Egg Reduction Rate (Percent [%]) Determined by Kato-Katz Method
timeFrame: Pre-treatment, Week 3 post-treatment
measure: Cohort 4a and Cohort 4b: Egg Reduction Rate (Percent [%]) Determined by Urine Filtration Technique
timeFrame: Pre-treatment, Weeks 3 and 5 post-treatment
measure: 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
timeFrame: at Week 3
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs
timeFrame: up to Day 40
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
timeFrame: up to Day 40
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline, Day 1
measure: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration and Hemoglobin
timeFrame: Baseline, Day 1
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline, Day 1
measure: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline, Day 1
measure: Change From Baseline in Hematology Parameters: Hematocrit, Lymphocytes/Leukocytes, Mixed Cells/Leukocytes, Neutrophils/Leukocytes
timeFrame: Baseline, Day 1
measure: Change From Baseline in Hematology Parameters: Leukocytes and Platelets
timeFrame: Baseline, Day 1
measure: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase and Aspartate Aminotransferase
timeFrame: Baseline, Day 1
measure: Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Direct Bilirubin
timeFrame: Baseline, Day 1
measure: Change From Baseline in Chemistry Parameter: C Reactive Protein
timeFrame: Baseline, Day 1
measure: Change From Baseline in Chemistry Parameters: Glucose, Urea and Urea Nitrogen
timeFrame: Baseline, Day 1
measure: Change From Baseline in Chemistry Parameter: Total Protein
timeFrame: Baseline, Day 1
measure: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine
timeFrame: Baseline, Day 1
measure: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine
timeFrame: Baseline, Day 1
measure: Change From Baseline in Urinalyses Parameter: Urobilinogen
timeFrame: Baseline, Day 1
measure: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure
timeFrame: Baseline, Week 3
measure: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: Baseline, Week 3
measure: Change From Baseline in Vital Sign: Respiratory Rate
timeFrame: Baseline, Week 3
measure: Change From Baseline in Vital Signs: Temperature
timeFrame: Baseline, Week 3
measure: Number of Participants With Reaction to Study Intervention Administration
timeFrame: Day 1
measure: Cohort 1a, Cohort 1b, Cohort 4a and Cohort 4b: Palatability Assessment Based on Visual Analog Scale (VAS) Score
timeFrame: Day 1
measure: Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-PZQ and S-PZQ
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Praziquantel (PZQ) Enantiomers: R-PZQ and S-PZQ
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Praziquantel (PZQ) Enantiomers: R-PZQ and S-PZQ
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
Other outcomes:
Locations:
city: Abidjan
country: Côte D'Ivoire
facility: Universitè de Cocody
city: Kisumu
country: Kenya
facility: Kemri Kisumu
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: