Efficacy and Safety of MOX/ALB vs. IVM/ALB Co-administration
Condition: Trichuriasis; Ascariasis; Hookworm Infections; Helminthes; Infestation, Intestinal
MeSH terms: Hookworm Infections; Ancylostomiasis; Trichuriasis; Ascariasis; Helminthiasis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of this randomized controlled trial is to provide evidence on the efficacy and safety
      of co-administered moxidectin and albendazole compared to co-administered ivermectin and
      albendazole, and to assess the efficacy of the drug combinations compared to monotherapies in
      adolescents aged 12-19 years against infection with T. trichiura.

      The efficacy of the different treatments will be determined 14-21 days, 5-6 weeks and 3
      months post-treatment. Two fecal samples will be collected at each time-point assessment. The
      geometric mean based egg reduction rate (ERR) of T. trichiura egg counts will be assessed by
      Kato-Katz microscopy pre-treatment and 14-21 days post-treatment.

      This trial will be conducted as a school-based study on Pemba Island (Zanzibar, Tanzania).
    

Detailed description: 
      We designed a non-inferiority trial to show that co-administered moxidectin and albendazole
      is non-inferior compared to co-administered ivermectin and albendazole in adolescents aged
      12-19 years on Pemba Island (Tanzania). From previous studies conducted by our group, we
      expect similar efficacies from the combination moxidectin/ albendazole compared to
      ivermectin/ albendazole. However, moxidectin might be advantageous in terms of the drug's
      longer half-life and in areas with possible emerging ivermectin resistance. This study will
      allow comparing the efficacy of the two available co-administrations and will provide further
      insights on the potential value of moxidectin/ albendazole. Our data will pave the way for
      possible large scale, multi country follow-up studies. As recommended for new combination
      therapies, we simultaneously assess superiority of the drug combinations compared to
      monotherapies.

      The primary objective is to demonstrate that co-administered moxidectin (8 mg) / albendazole
      (400 mg) is non-inferior to ivermectin (200 µg/kg) / albendazole (400 mg) in terms of egg
      reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days
      post-treatment in adolescents aged 12-19 years using a non-inferiority margin of 2
      percentage-points.

      The secondary objectives of the trial are:

        1. Efficacy assessments of combination therapies require demonstration of superiority
           against the respective monotherapies. Therefore, the trial has five different treatment
           groups: moxidectin (8 mg) / albendazole (400 mg) combination, ivermectin (200 µg/kg) /
           albendazole (400 mg) combination, albendazole (400 mg) monotherapy, ivermectin (200
           µg/kg) monotherapy and moxidectin (8 mg) monotherapy.

        2. to determine the CRs of the drug regimens against T. trichiura

        3. to evaluate the safety and tolerability of the treatment

        4. to determine the CRs and ERRs of the treatment schemes in study participants infected
           with hookworm and A. lumbricoides

        5. to investigate potential extended effects on follow-up helminth prevalences (5-6 weeks
           and 3 months post-treatment) of the treatment regimens

        6. to assess diagnostic performance and compare CRs based on egg counts retrieved from
           novel diagnostic tools (FECPAK-G2 and/or PCR) compared to standard microscopy

        7. to characterize population PK parameters, as well as drug-drug interactions of active
           study treatments following single and co-administration in T. trichiura infected
           adolescents. If a dose-response is observed, a PK/PD analysis will further be performed

      The study will be carried out in adolescents aged 12-19 years attending secondary schools on
      Pemba Island, Tanzania. After consenting, all participants will be asked to provide two stool
      samples (within a maximum of 7 days) at each time-point assesment. From each stool specimen,
      duplicate Kato-Katz thick smears (41.7 mg each) will be prepared and read under a microscope
      for eggs of T. trichiura, A. lumbricoides and hookworm by experienced technicians.

      After randomization, all eligible adolescents will be treated with the respective single or
      combination treatment regimen according to their assigned treatment arm at day 0.

      All drugs will be administered in the presence of the PI and/ co-PI, and ingestion confirmed.
      This will be recorded with the time and date of dosing. Participants will be kept for 3 hours
      after treatment administration to observe any possible acute AEs and reassessment will be
      done at 24h post-treatment. Additionally, interviews will be conducted to determine the
      emergence of clinical symptoms such as headache, abdominal pain, itching, nausea, vomiting
      and diarrhea directly before treatment within the scope of baseline assessment. At 3 and 24
      hours after treatment and retrospectively at days 14 - 21 as well as 5-6 weeks and 3 months
      post-treatment, participants will again be interviewed for the assessment of adverse events
      (AEs).

      Egg reduction rate calculated from the geometric means of co-administered moxidectin/
      albendazole and ivermectin/ albendazole against T. trichiura assessed at 14-21 days
      post-treatment is the primary endpoint in our study.
    

Intervention name(s): moxidectin (8 mg) / albendazole (400 mg); ivermectin (200 µg/kg) / albendazole (400 mg); ALBENDAZOLE 400 Mg ORAL TABLET [ZENTEL]; ivermectin (200 µg/kg); moxidectin (8 mg)
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Combination therapy of moxidectin (8 mg using 2 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0; Combination therapy of ivermectin ((200 µg/kg), 3 mg tablet) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0; Monotherapy of albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0; Monotherapy of ivermectin ((200 µg/kg), 3 mg tablet) administered orally at day 0; Monotherapy of moxidectin (8 mg, using 2 mg tablets) administered orally at day 0
Other intervention name(s): Zentel®; Stromectol® / Zentel®; Zentel®; Stromectol®
Intervention MeSH terms: Ivermectin; Albendazole; Moxidectin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: T. trichiura; A. lumbricoides; Hookworm; Soil-transmitted Helminths; Albendazole; Ivermectin; Moxidectin; Intestinal parasites; Anthelmintics