2nd Joint Call: Moxistrong
Strongyloides stercoralis belongs to the soil-transmitted helminths and is the most neglected helminth infection among the neglected tropical diseases. It occurs almost worldwide and may result in long-lasting infections, and significant morbidity. Today, drug treatments, combined with health education programs, remain the core control strategy. The current recommended treatments are a single dose of ivermectin or multiple doses of albendazole, which has a lower efficacy compared to ivermectin. Since drug resistance is a threat it is important to develop treatment alternatives. Among new candidates in the human anthelminthic drug development pipeline, moxidectin, a macrocyclic lactone might be an excellent alternative. In an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin an excellent cure rate was observed against S. stercoralis.
The overarching goal of this project is to assemble for the first time key data on the safety and efficacy and pharmacokinetics of moxidectin for the treatment of strongyloidiasis. The project involves four highly multi-disciplinary, interlinked objectives. 1.) What is the efficacy and safety of ascending moxidectin doses (2-12 mg versus placebo) against S. stercoralis infections in adults? 2. Can dried blood spots (DBS) be used to analyse pharmacokinetic (PK) properties of moxidectin? 3. What are key PK parameters of moxidectin in patients infected with S. stercoralis? 4. What is the safety and efficacy of moxidectin against S. stercoralis compared to the drug of choice ivermectin?
Research questions are embedded in one Phase 2a and two Phase 2b clinical trials. A Phase 2a dose-finding trial will be conducted to determine the efficacy and safety of ascending single, oral doses of moxidectin versus placebo in Lao PDR in 210 adults infected with S. stercoralis. The primary outcome is to assess the efficacy of 2-12 mg moxidectin versus placebo in terms of cure rate against S. stercoralis. Secondary outcomes are the tolerability of the treatment regimens and PK properties. For this purpose venous blood will be withdrawn by cannulation from 15 adults in the Phase 2a study at 0, 2, 4, 8, 24 and 72 hours, 7 and 21 days post-treatment with moxidectin in the 8 mg study arm. From the same participants and of 15 patients in the other treatment arms DBS samples will be taken at the same time points. Once the optimal dose of moxidectin has been identified in the Phase 2a trial a Phase 2b trial will be conducted in Laos and Cambodia. This study will be a non-inferiority trial and include 245 patients treated with moxidectin, ivermectin or placebo. 35 patients will be included in the PK studies.
The Moxistrong partners are:
Prof. Jennifer Keiser : Swiss Tropical and Public Health Institute, Switzerland
Dr. Somphou Sayasone : Lao Tropical and PublicHealth Institute, Laos PDR
Dr. Virak Khieu : National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Jennifer Keiser: firstname.lastname@example.org