Efficacy and Safety of Moxidectin, Synriam, Synriam-Praziquantel versus Praziquantel against Schistosoma haematobium and S. mansoni Infections: A Randomized, Exploratory Phase 2 Trial

Background: Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies. Methodology: We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Côte d’Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus praziquantel or praziquantel. Principal Findings: 128 adolescents (age: 12–17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus praziquantel and praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus praziquantel and praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (praziquantel). Conclusion/Significance: Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni. Author Summary: Schistosomiasis is a parasitic infection that affects millions of people all over the world and it is due to schistosomes, helminths (worms) that infect the intestine and the urinary bladder. Treatment options are limited, with praziquantel being the only used drug. The antimalarial Synriam and the anthelminthic moxidectin revealed good action against this worm in previous studies. We conducted two studies in Schistosoma mansoni and S. haematobium-infected adolescents in Côte d’Ivoire. Subjects positive for the infection were allocated by chance to the four groups of treatment (moxidectin, Synriam, Synriam plus praziquantel or praziquantel); participants did not know which drug they took. Our aim was to calculate how many participants were negative after the treatment and how did the intensity of infection change before and after treatment. Each subject provided stools and urines for examination. 128 adolescents were included in each study. Moxidectin and Synriam did not work well against S. haematobium. Against S. mansoni, only a small part of the participants were negative after treatment in all treatment groups, but the intensity of infections were reduced. Further studies are needed to better understand this result.