Efficacy and Safety of MOX/ALB Co-administration
Condition: Trichuriasis; Ascariasis; Hookworm Infections
MeSH terms: Hookworm Infections; Ancylostomiasis; Trichuriasis; Ascariasis
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is a double-blind randomized controlled superiority trial aiming at providing
      evidence on the efficacy and safety of co-administered moxidectin and albendazole versus
      albendazole monotherapy (standard of care) against whipworm (T. trichiura) infections in
      adolescents and adults (12-60 years) in Côte d'Ivoire. One arm of patients will be treated
      with albendazole-ivermectin.

      As measure of efficacy of the treatment the cure rate (percentage of egg-positive subjects at
      baseline who become egg-negative after treatment) will be determined 14-21 days
      post-treatment.
    

Detailed description: 
      This study is a double-blind randomized clinical trial which aims at providing evidence on
      the efficacy and safety of co-administered moxidectin and albendazole versus albendazole
      monotherapy (standard of care) against T. trichiura infections in adolescents and adults
      (12-60 years) in Côte d'Ivoire. Additionally, this study aims to substantiate evidence on the
      efficacy and safety of co-administered ivermectin and albendazole compared to albendazole
      monotherapy against T. trichiura in the same age group.

      The primary objective of the trial is to comparatively assess the efficacy in terms of cure
      rate (CR) against T. trichiura infections among adolescents and adults (aged 12 to 60 years)
      of moxidectin/albendazole combination therapy and albendazole monotherapy.

      The secondary objectives of the trial are to compare the egg reduction rates (ERR) of these
      treatment regimens (moxidectin/albendazole combination therapy vs. albendazole monotherapy)
      against T. trichiura, to assess the CRs and ERRs in T. trichiura-infected participants given
      ivermectin/albendazole combination therapy compared to those given albendazole monotherapy,
      to determine the CRs and ERRs of the drugs in study participants co-infected with A.
      lumbricoides and hookworm, and to evaluate the safety and tolerability of the treatment
      regimens. In addition, this study aims to characterize population pharmacokinetics and
      drug-drug interactions of the study drugs albendazole and ivermectin in T. trichiura infected
      adolescents (aged 12 to 20 years), to evaluate pharmacogenomics of ivermectin using whole
      genome sequencing, and to assess the effect of the gut microbiota on pharmacokinetics
      parameters and treatment outcome (CRs and ERRs), and drug-specific off-target effects of
      anthelmintic treatment on gut microbial communities in post-treatment samples.

      After obtaining informed consent from individual/parents and/or caregivers, the medical
      history of the participants will be assessed with a standardized questionnaire, in addition
      to a clinical examination carried out by the study physician before treatment. Enrollment
      will be based on two stool samples, which will be collected, if possible, on two consecutive
      days or otherwise within a maximum of 5 days. All stool samples will be examined with
      duplicated Kato-Katz thick smears by experienced laboratory technicians.

      Randomization of participants into the three treatment arms will be stratified according to
      intensity of infection. All participants will be interviewed before treatment, 3 and 24 hours
      and 14-21 days after treatment about the occurrence of adverse events. The efficacy of the
      treatment will be determined 14-21 days post-treatment by collecting another two stool
      samples.

      The primary analysis will include all participants with primary end point data (available
      case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be
      calculated as the percentage of egg-positive subjects at baseline who become egg-negative
      after treatment. Differences among CRs between treatment arms will be analysed using crude
      and adjusted logistic regression modeling (adjustment for age, sex and weight).

      Geometric and arithmetic mean egg counts will be calculated for the different treatment arms
      before and after treatment to assess the corresponding ERRs.

      Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence
      intervals (CIs) for differences in ERRs.
    

Intervention name(s): Moxidectin 2 mg Oral Tablet; Albendazole 400 mg Oral Tablet; Ivermectin 3 mg Oral Tablet
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Tablets of 2 mg moxidectin; Tablets of 400 mg albendazole; Tablets of 3 mg ivermectin
Other intervention name(s): Zentel®; Stromectol®
Intervention MeSH terms: Ivermectin; Albendazole; Moxidectin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Albendazole; Moxidectin; Ivermectin; Anthelmintics; T. trichiura; A. lumbricoides; Hookworm; Whipworm; Soil-transmitted helminths