Praziquantel in Children Under Age 4

NCT03640377 | Completed Phase 2 Results DMC

• 2 other identifiers: 403818R01HD095562
• Study Type: interventional
• Target: 354
• Locations: 2 countries
• Sites: 2

Brief Summary

The overall goals of this proposal are to conduct a trial to address the significant gaps with respect to our understanding of best approaches to treatment of children ages 1-4 with intestinal schistosomiasis. Over 200 million individuals worldwide are infected with one of three predominant species of schistosomes, with over half of infections occurring in children. Recent studies have highlighted the fact that many children experience first infections before the age of two, with the prevalence of infection among children under four mirroring the prevalence of older children from the same community. Importantly, praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, is only FDA approved among adults and children over the age of four. Only one small study led by co-PI Bustinduy has evaluated the pharmacokinetic/pharmacodynamics (PK/PD) of PZQ in children. That study, conducted among children ages 3-8, strongly suggests that the current dose of 40 mg/kg is insufficient, with lower cure rates than found at 60 mg/kg. In endemic settings, PZQ is most often administered as part of school based, or community wide preventive chemotherapy campaigns. Currently, none of the 28 schistosomiasis endemic African nations or The Philippines includes children under the age of four in control programs. The reasons for this are multifactorial and include a) lack of sufficient PK/PD data in this age group, with none in children under three, b) lack of safety data at a dose of 80 mg/kg, c) lack of data addressing the impact of treatment on key growth and nutritional outcomes in this vulnerable age group hampering prioritization of treatment, d) no PK/PD studies conducted in the context of pediatric S. japonicum and e) FDA labeling that does not include young children. The goals of this proposal are to conduct a randomized, controlled Phase II trial to be conducted in an S. mansoni endemic region of Uganda with N=300 children ages 1-4, that will address many of the current gaps that are hindering treatment of young children. Specifically in SA1 we will 1) assess PK/PD of PZQ dosing among children under the age of 4 at doses of 40 versus 80 mg/kg, 2) expand PD endpoints to include state of the art antigen tests and morbidity outcomes, 3) assess the PK/PD of both PZQ enantiomers, and 4) address the innovative hypothesis that environmental enteropathy (EE) contributes to the significant inter-individual variability observed in PZQ PK/PD. In SA2, we will 1) assess the safety of PZQ administered at 80 mg/kg in two large cohorts of very young children, 2) assess the impact of two different treatment intervals (6 vs 12 months) on nutritional status, growth, and anemia risk, and 3) address innovative hypotheses regarding mechanisms through which schistosomiasis contributes to morbidity in this age group including EE and gut microbial translocation with consequent systemic immune activation.

Conditions

Schistosomiasis Mansoni; Schistosoma Japonicum Infection; Schistosomiasis

Outcome Measures

Primary Outcomes (2)

• Treatment Efficacy

  Treatment efficacy as captured by egg reduction rate with the post treatment egg count assessed four weeks after treatment baseline treatment only. This is the calculated as 1 - (Post-treatment mean egg count / pre-treatment mean egg count) x 100%

  Four weeks after baseline treatment

• Treatment Efficacy - Cure Rate

  Efficacy of treatment as captured by cure rate 4 weeks after treatment at baseline. Cure rate is the percent of participants in a group who have no infection (zero eggs per gram of stool) four weeks after treatment at baseline

  Four weeks after baseline treatment

Secondary Outcomes (4)

• Hemoglobin

  12 months following treatment at enrollment/baseline

• Age and Gender Adjusted Linear Growth

  12 months following treatment at enrollment/baseline

• Age and Gender Adjusted Nutritional Status

  12 months following treatment at enrollment/baseline

• Fecal Calprotectin

  12 months following treatment at enrollment/baseline

Study Arms (4)

Praziquantel 40 mg/kg dose only baseline treatment

ACTIVE COMPARATOR

75 children will receive 40 mg/kg Praziquantel at baseline as single treatment and placebo six months following baseline

Drug: Praziquantel

Praziquantel 80 mg/kg dose only baseline treatment

ACTIVE COMPARATOR

75 children will receive 80 mg/kg Praziquantel at baseline as single treatment and placebo six months following baseline

Drug: Praziquantel

Praziquantel 40 mg/kg dose at baseline and 6 months

ACTIVE COMPARATOR

75 children will receive 40 mg/kg Praziquantel at baseline and again six months later.

Drug: Praziquantel

Praziquantel 80 mg/kg dose at baseline and 6 months

ACTIVE COMPARATOR

75 children will receive 80 mg/kg Praziquantel at baseline and again six months later.

Drug: Praziquantel

Interventions

Praziquantel DRUG

Praziquantel given as crushed tablets (40 or 80 mg/kg)

Praziquantel 40 mg/kg dose at baseline and 6 months; Praziquantel 40 mg/kg dose only baseline treatment; Praziquantel 80 mg/kg dose at baseline and 6 months; Praziquantel 80 mg/kg dose only baseline treatment

Eligibility Criteria

• Age: 12 Months - 48 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• S. mansoni infection by urine CCA
• Otherwise healthy as determined by history and physical examination conducted by the study physician at the second stage screening
• Age 12-48 months inclusive
• Parental consent to participate.

You may not qualify if:

• Parental inability to provide informed consent
• Significant disease/illness as determined by history or physical exam. This includes a severe acute illness or chronic disease as defined by greater than 3 months duration and significantly impacting a child's daily activities.
• Severe wasting as defined by WHZ \< -3,
• Severe anemia (hemoglobin \< 7 g/dL)
• Exposure to immuno-modulatory therapeutics.

Sponsors & Collaborators

• Rhode Island Hospital: lead
• University of Liverpool: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Research Institute for Tropical Medicine, Philippines: collaborator
• Medical Research Council: collaborator

Study Sites (2)

Medical Research Council

Entebbe, 3FC6+Q3C,, Uganda

Location

London School of Tropical Hygiene and Medicine

London, United Kingdom

Location

Related Publications (2)

• Webb EL, Edielu A, Wu HW, Kabatereine NB, Tukahebwa EM, Mubangizi A, Adriko M, Elliott AM, Hope WW, Mawa PA, Friedman JF, Bustinduy AL. The praziquantel in preschoolers (PIP) trial: study protocol for a phase II PK/PD-driven randomised controlled trial of praziquantel in children under 4 years of age. Trials. 2021 Sep 6;22(1):601. doi: 10.1186/s13063-021-05558-1.

  PMID: 34488846 BACKGROUND

• Bustinduy AL, Edielu A, Ayebazibwe GK, Nakyesige R, Anguajibi V, Mpooya S, Nassuna J, Adriko M, Elliott A, van Dam G, Corstjens P, Pach S, Wu H, Colt S, Mawa PA, Muheki E, Kabatereine NB, Webb EL, Friedman JF. Safety and efficacy of praziquantel 40 mg/kg versus 80 mg/kg in preschool-aged children with intestinal schistosomiasis in Uganda: a 2 x 2 factorial, double-blind, placebo-controlled, phase 2 randomised trial. Lancet Glob Health. 2025 Jun;13(6):e1091-e1100. doi: 10.1016/S2214-109X(25)00095-6.

  PMID: 40412398 RESULT

MeSH Terms

Conditions

Schistosomiasis; Schistosomiasis mansoni; Schistosomiasis japonica

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: Dr. Jennifer Friedman
• Organization: Center for International Health Research at Brown Health

Jennifer_Friedman@Brown.edu

401 444 7990

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Tablets will be crushed and given with orange juice
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for International Health Research

Model Details: Children ages 12-48 months who are infected with S. japonicum (Philippines) or S. mansoni (Uganda) will be randomized to receive either 40 or 60 mg/kg of praziquantel at baseline. Six months later, half of each group will receive second treatment at same dose or placebo.

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: August 21, 2018
• Study Start: February 1, 2021
• Primary Completion: February 5, 2024
• Study Completion: June 1, 2024
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within one year of trial completion and up to five years after.

Locations

GB (1); UG (1)