Efficacy and Safety of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
Condition: Strongyloides Stercoralis Infection
MeSH terms: Infections; Strongyloidiasis
Study type: Interventional
Phase: Phase 3

Summary: 
      The study is an extension to the study StrongMoxi NCT04056325 and entails modifications based
      on the outcome of NCT04056325 part A.

      The study is a phase 3, double-blinded and randomized clinical trial conducted in Cambodia.
      It aims at providing evidence on efficacy, safety and pharmacokinetic measures of 8 mg of
      moxidectin compared to 200 μg/kg ivermectin in adults infected with S. stercoralis. The
      efficacy of the treatment will be assessed by collecting three stool samples once
      per-treatment and once 21-28 days post-treatment. The stool samples will be analyzed by a
      quantitative duplicate Baermann assay.
    

Detailed description: 
      The study is a phase 3 trial and will determine the efficacy and safety of:

      8 mg of moxidectin in comparison to the standard treatment dose of ivermectin (200 μg/kg) in
      adults infected with S. stercoralis and to measure moxidectin disposition in adults using a
      microsampling device.

      Our primary objective is to demonstrate non-inferiority in terms of cure rate (CR) against S.
      stercoralis in adults of an oral 8 mg of moxidectin compared to 200 μg/kg of ivermectin.

      The secondary objectives of the trial are:

        1. to evaluate the safety and tolerability of moxidectin

        2. to compare the larval reduction rate (LRR) of the two different treatment groups against
           S. stercoralis

        3. to evaluate the CRs of the different treatment drugs and regimens against
           soil-transmitted helminths (STH) co-infections.

        4. to investigate potential extended effects on follow-up helminth prevalence at 42-49 and
           63-70 days post-treatment

        5. to relate socioeconomic characteristics (SES), access to sanitation, water facilities,
           hygiene to baseline infection intensity.

        6. to determine the larval excretion pattern till day 70 in the moxidectin treatment arm,
           determined at every second day between day zero and 70 post-treatment in a subset of 50
           adults.

        7. to determine the origin of the remaining worm burden after treatment to treatment
           failure and reinfection based on genetic profiling.

      Three stool samples will be collected at baseline analysed in duplicates by a quantitative
      Baermann method for S. stercoralis infection. Co-infection with other Helminths species will
      be identified using duplicate Kato-Katz thick smears on two stool samples. The medical
      history of the participants will be assessed with a standardized questionnaire, in addition
      to a clinical and physical examination carried out by the study physician shortly before the
      treatment day. Each participant will be asked to provide a finger-prick blood sample for
      haemoglobin measurements at baseline. Enrolled participants will be treated with either 8 mg
      of moxidectin or with the standard treatment ivermectin (200 μg/kg). The adults will be
      interviewed a) before treatment, 2-3 and 24 hours as well as 14-21, 42-49 and 63-70 days
      after treatment about the occurrence of adverse events. The efficacy of the treatment will be
      determined 14-21 days of post-treatment. All stool samples will be examined with quantitative
      sixtuplicate Baermann assays and quadruplet Kato-Katz thick smears. At 42-49 and 63-70 days
      post-treatment another three stool samples will be collected and quantified for S.
      stercoralis larvae using Baermann assay to assess potential long-term benefits of the study
      drugs and treatment regimen. Of 50 adults in the moxidectin arm only, additional stool
      samples will be collected every second day between treatment and 70 days post treatment to
      evaluate larval secretion patterns.

      To all participating households, a brief questionnaire will be administered assessing
      information on socioeconomic characteristics (SES) and access to sanitation, water
      facilities, and hygiene behaviour.

      An available case analysis (full analysis set according to the intention to treat principle)
      will be performed, including all participants with primary endpoint data.

      CRs will be calculated as the percentage of larvae-positive subjects at baseline who become
      larvae-negative after treatment, assessed 14-21 days post-treatment by sextuplicate Baermann.
      Uncertainty estimates around the differences among CRs will be assessed using melded
      confidence intervals with mid-p correction. The non-inferiority.
    

Intervention name(s): Moxidectin 2 mg; Ivermectin 3 mg; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Monotherapy, oral administration, single-dose, fixed-dose, 4 tablets of 2 mg each to yield an 8 mg final dose.; Monotherapy, oral administration, single-dose, weight dependent, The number of tablets will be adjusted according to the patients' weight to yield 200 ug/kg final dose.; Monotherapy, oral administration, single dose, matching number of tablets to either moxidectin or ivermectin
Intervention MeSH terms: Ivermectin; Moxidectin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel study with 2 treatment arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment