A Phase 2 interventional study of Praziquantel in Schistosomiasis, Schistosomiasis Mansoni and Schistosoma Japonicum Infection, sponsored by Rhode Island Hospital. Completed at 2 sites in 2 countries. Open to participants aged 12 Months to 48 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-23.
Sponsored by Rhode Island Hospital · Phase 2, Interventional, and Treatment
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.
Over 200 million individuals worldwide are infected with one of three predominant species of schistosomes, with over half of infections occurring in children.1 Recent studies have highlighted the fact that many children experience their first infections before the age of two, with the prevalence of infection among children under four mirroring the prevalence of older children and adults from the same community.2 Importantly, schistosomiasis has been implicated as a cause of linear growth stunting, undernutrition, anemia, and deficits in neurodevelopment among children over the age of four, representing a significant proportion of the global burden of disease due to schistosomiasis.3 Little is known with respect to the impact of schistosomiasis on key morbidities among the highly vulnerable group of children under four.
In the 1980s, Praziquantel (PZQ) was approved for the treatment of schistosomiasis among adults and children ages four and older, and remains FDA approved only for this age group. In 2008, the WHO funded studies to address the safety and parasitologic efficacy of PZQ in the context of S. haematobium and S. mansoni in young children. Based on these and other studies, the WHO in 2011 issued a report recommending that pre-school age children be treated as part of "regular health services."4 This recommendation was based on studies that did not a) evaluate pharmaco-kinetics/dynamics (PK-PD) in this age group, b) evaluate parasitologic efficacy in S. japonicum or c) evaluate the impact of treatment on key schistosomiasis-related morbidities. Since that time, co-PI Bustinduy led the first study of the PK-PD of PZQ at both 40 and 60 mg/kg dosing among children ages 3-8. Results from that study, albeit small, showed that higher doses are likely needed, particularly for younger children. Authors urged further study of higher doses in this age group, the causes of the significant inter-subject variability in PK-PD, better PD indices linking drug exposure to treatment effects, and enantiomer activity across all three species before introduction of monoenantiomeric formulations.5
Thus, significant lacunae remain with respect to treatment of pre-school age children, which contribute to the persistent exclusion of this vulnerable age group from preventive chemotherapy campaigns, with none of the 28 schistosomiasis endemic African nations or The Philippines currently including children under the age of four in control programs.2 In this application, we propose a trial to investigate the off label use of PZQ in children under the age of four. The trial will be conducted at two sites, with high prevalence of intestinal schistosomiasis due to S. mansoni (Uganda) and S. japonicum (The Philippines) employing a two arm single blind, placebo controlled modified cross-over trial design among N=600 children ages 1-4. Children who are infected with schistosomiasis will be randomized at baseline to receive 40 or 80 mg/kg of PZQ. At six months, we will re-randomize half of each baseline group to receive a treatment at the same dose or placebo. This will allow us to evaluate the impact of 6 versus 12 month treatment intervals on key measures of morbidity which, importantly, will inform frequency of treatment needed in this young age group. Successful execution of the following specific aims for this trial will address the significant aforementioned gaps:
SA1 To assess the PK/PD of PZQ administered at different dose regimens. SA1a To measure drug efficacy as per standard parasitological endpoints (Cure Rate and Egg Reduction Rate) at 4 +/- 1 weeks post-PZQ.
SA1b To expand PD endpoints for drug efficacy to include state-of-the art antigen tests to accurately capture residual worm burden (Circulating Cathodic and Anodic Antigens (CCA and CAA)).
SA1c To evaluate the PK/PD of both PZQ enantiomers given the concern that this varies across species and has varied in studies of S. mansoni.
SA1d To assess the role of environmental enteropathy in inter-individual variability in PZQ area under the curve (AUC) demonstrated in this age group.
SA2 To assess the safety and impact of PZQ treatment (dose and interval) on key measures of morbidity 6 and 12 months after initial treatment and mechanisms mediating morbidity.
SA2a To further evaluate the safety of higher PZQ dosing (60 mg/kg), particularly among the unstudied group of very young children ages 1-2.
SA2b To evaluate the impact of different doses (40 vs. 80 mg/kg) and varying dosing intervals (every 6 or 12 months) on iron status, hemoglobin, and age and gender adjusted longitudinal growth and nutritional status as captured by height and weight for age, and weight for height z-scores as determined by WHO Anthro.
SA2c To evaluate the mechanistic role of environmental enteropathy (EE) in the pathogenesis of schistosomiasis related morbidities. We will capture state of the art biomarkers of EE including fecal calprotectin, urine lactulose:mannitol ratio, serum endotoxin, serum endotoxin core antibody, and pro-inflammatory cytokines and employ Path Modeling techniques to identify mechanistic pathways.
79 studies on the registry are indexed under Schistosomiasis; 14 are open to participants now.
This study's enrollment of 354 is above the median of 289 across 52 interventional studies indexed under Schistosomiasis.
Browse Schistosomiasis studies →Rhode Island Hospital is the lead sponsor of 191 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 2 (17%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
75 children will receive 40 mg/kg Praziquantel at baseline as single treatment and placebo six months following baseline
Drug: Praziquantel
75 children will receive 80 mg/kg Praziquantel at baseline as single treatment and placebo six months following baseline
Drug: Praziquantel
75 children will receive 40 mg/kg Praziquantel at baseline and again six months later.
Drug: Praziquantel
75 children will receive 80 mg/kg Praziquantel at baseline and again six months later.
Drug: Praziquantel
Praziquantel given as crushed tablets (40 or 80 mg/kg)
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%
Time frame: 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
Time frame: Four weeks after baseline treatment
Hemoglobin
Assess impact of varying doses and frequency of dosing on hemoglobin measured 12 months after baseline treatment
Time frame: 12 months following treatment at enrollment/baseline
Age and Gender Adjusted Linear Growth
Assess impact of varying doses and frequency of dosing on linear growth as captured by Z-score. A Z-score is the standard deviation from age (months) and sex mean from the World Health Organization's (WHO) Multicentre Growth Reference Study which derived the WHO "Anthro" reference. That reference assessed approximately 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA) and provides a single international standard that represents the best description of physiological growth for all children from birth to five years of age and to establish the breastfed infant as the normative model for growth and development. For Z-scores presented, 0 represents the population mean for the healthy Anthro reference curve and positive values are taller children while negative are shorter. A Z score of -2.0 or below defines "stunting" or children -2 standard deviations below this healthy reference population.
Time frame: 12 months following treatment at enrollment/baseline
Age and Gender Adjusted Nutritional Status
Assess impact of varying doses and frequency of dosing on nutritional as captured by weight for height Z-score. A Z-score is the standard deviation from age (months) and sex mean from the World Health Organization's (WHO) Multicentre Growth Reference Study which derived the WHO "Anthro" reference. That reference assessed approximately 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA) and provides a single international standard that represents the best description of physiological growth for all children from birth to five years of age and to establish the breastfed infant as the normative model for growth and development. For Z-scores presented, 0 represents the population mean for the healthy Anthro reference curve and positive values are better nourished children. A Z score of -2.0 or below defines "wasting" or children -2 standard deviations below mean of health reference
Time frame: 12 months following treatment at enrollment/baseline
Fecal Calprotectin
A measure of gut inflammation that is measured on stool samples and captures intestinal inflammation largely caused by neutrophils that migrate to the gut
Time frame: 12 months following treatment at enrollment/baseline
| Milestone | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Started | 88 | 86 | 89 | 91 |
| Completed | 72 | 72 | 80 | 72 |
| Not completed | 16 | 14 | 9 | 19 |
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%
| percentage change | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Treatment Efficacy | 96 (95 to 97) | 98 (98 to 99) | 96 (95 to 97) | 98 (98 to 99) |
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
| Percent of participants | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Treatment Efficacy - Cure Rate | 67 | 90 | 67 | 90 |
Assess impact of varying doses and frequency of dosing on hemoglobin measured 12 months after baseline treatment
| grams/decilter | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Hemoglobin | 10.3 ± 1.4 | 10.3 ± 1.4 | 10.4 ± 1.3 | 10.4 ± 1.3 |
Assess impact of varying doses and frequency of dosing on linear growth as captured by Z-score. A Z-score is the standard deviation from age (months) and sex mean from the World Health Organization's (WHO) Multicentre Growth Reference Study which derived the WHO "Anthro" reference. That reference assessed approximately 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA) and provides a single international standard that represents the best description of physiological growth for all children from birth to five years of age and to establish the breastfed infant as the normative model for growth and development. For Z-scores presented, 0 represents the population mean for the healthy Anthro reference curve and positive values are taller children while negative are shorter. A Z score of -2.0 or below defines "stunting" or children -2 standard deviations below this healthy reference population.
| Z score | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Age and Gender Adjusted Linear Growth | -0.8 ± 1.4 | -0.7 ± 1.3 | -0.8 ± 1.4 | -0.7 ± 1.3 |
Assess impact of varying doses and frequency of dosing on nutritional as captured by weight for height Z-score. A Z-score is the standard deviation from age (months) and sex mean from the World Health Organization's (WHO) Multicentre Growth Reference Study which derived the WHO "Anthro" reference. That reference assessed approximately 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA) and provides a single international standard that represents the best description of physiological growth for all children from birth to five years of age and to establish the breastfed infant as the normative model for growth and development. For Z-scores presented, 0 represents the population mean for the healthy Anthro reference curve and positive values are better nourished children. A Z score of -2.0 or below defines "wasting" or children -2 standard deviations below mean of health reference
| Z score | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Age and Gender Adjusted Nutritional Status | 0.3 ± 0.9 | 0.4 ± 0.9 | 0.3 ± 0.9 | 0.4 ± 0.9 |
A measure of gut inflammation that is measured on stool samples and captures intestinal inflammation largely caused by neutrophils that migrate to the gut
| percentage with calprotectin >50 ug/g | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| Fecal Calprotectin | 46 | 29 | 46 | 29 |
Collected over For one year during the 12 months following the first treatment at Baseline. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Praziquantel 40 mg/kg Dose Only Baseline Treatment | 0/88 (0%) | 0/88 (0%) | 9/88 (10.2%) |
| Praziquantel 80 mg/kg Dose Only Baseline Treatment | 1/86 (1.2%) | 1/86 (1.2%) | 8/86 (9.3%) |
| Praziquantel 40 mg/kg Dose at Baseline and 6 Months | 0/89 (0%) | 0/89 (0%) | 10/89 (11.2%) |
| Praziquantel 80 mg/kg Dose at Baseline and 6 Months | 0/91 (0%) | 0/91 (0%) | 8/91 (8.8%) |
| Event | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| malariaBlood and lymphatic system disorders | 0/88 | 1/86 | 0/89 | 0/91 |
| Event | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months |
|---|---|---|---|---|
| liver function testsHepatobiliary disorders | 9/88 | 8/86 | 10/89 | 8/91 |
all children enrolled were infected with S. Mansoni as determined by Kato Katz and then randomly allocated to four treatment arms.
| Age, Categorical(Participants) | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months | Total |
|---|---|---|---|---|---|
| <=18 years | 88 | 86 | 89 | 91 | 354 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months | Total |
|---|---|---|---|---|---|
| Female | 44 | 43 | 44 | 46 | 177 |
| Male | 44 | 43 | 45 | 45 | 177 |
| Race (NIH/OMB)(Participants) | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 88 | 86 | 89 | 91 | 354 |
| White | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Praziquantel 40 mg/kg Dose Only Baseline Treatment | Praziquantel 80 mg/kg Dose Only Baseline Treatment | Praziquantel 40 mg/kg Dose at Baseline and 6 Months | Praziquantel 80 mg/kg Dose at Baseline and 6 Months | Total |
|---|---|---|---|---|---|
| Uganda | 88 | 86 | 89 | 91 | 354 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Data from the trial will be made available to interested investigators following IRB approval to provide these de-identified data. Specifically, after research data set has been cleaned, finalized, and all identifiers removed, the PIs will provide timely release and sharing of the final research data for use by other researchers. In addition, this study will generate samples collected young children. Upon discussion with the Principal Investigators and based on availability of samples, residual stored samples may be shared following IRB approval to provide these de-identified samples to interested researchers.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Within one year of trial completion and up to five years after.
Ran from Feb 2021 to primary completion in Feb 2024, 36 months.
Results were first posted in Apr 2026, 2 years 2 months after primary completion.
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Studies of the drug tested here: Praziquantel