Efficacy and Safety of MOX/ALB vs. IVM/ALB Co-administration

January 31, 2022 updated by: Jennifer Keiser

Efficacy and Safety of Moxidectin and Albendazole Compared to Ivermectin and Albendazole Co-administration in Adolescents Infected With Trichuris Trichiura: a Randomized Controlled Trial

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

536

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tanzania
    • Pemba
      • Chake Chake, Pemba, Tanzania
        • Public Health Laboratory Ivo de Carneri

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 17 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged between 12 and 19 years.
  • Written informed consent signed by either parents/caregivers for underage adolescents (aged 12-17 years) or by the participant him/herself (18-19 years of age); and written assent by underage participant.
  • Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and on three follow-up assessments (14-21 days, 5-6 weeks and 3 months after treatment).
  • Willing to be examined by a study physician prior to treatment.
  • At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura and infection intensities of at least 48 EPG.

Exclusion Criteria:

  • No written informed consent by individual or caregiver and/or no written assent by minors
  • Presence or signs of major systemic illnesses, e.g. body temperature ≥ 38°C, severe anemia (below 80g/l Hb according to WHO) upon initial clinical assessment.
  • History of acute or severe chronic disease.
  • Recent use of anthelmintic drug (within past 4 weeks).
  • Attending other clinical trials during the study.
  • Pregnancy, lactating, and/or planning to become pregnant within the next 6 months.
  • Known allergy to study medications (i.e. albendazole, ivermectin or moxidectin).
  • Taking medication with known interaction on study drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: moxidectin (8 mg) / albendazole (400 mg)
Combination therapy of moxidectin (8 mg using 2 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
Drug: moxidectin (8 mg) / albendazole (400 mg)
Combination therapy of moxidectin (8 mg using 2 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
Other Names:
  • Zentel®
Active Comparator: B: ivermectin (200 µg/kg) / albendazole (400 mg)
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using 3 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
Drug: ivermectin (200 µg/kg) / albendazole (400 mg)
Combination therapy of ivermectin ((200 µg/kg), 3 mg tablet) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
Other Names:
  • Stromectol® / Zentel®
Active Comparator: C: albendazole (400 mg)
Monotherapy of albendazole (400 mg) administered orally at day 0 Other names: Zentel®
Drug: ALBENDAZOLE 400 Mg ORAL TABLET [ZENTEL]
Monotherapy of albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
Other Names:
  • Zentel®
Active Comparator: D: ivermectin (200 µg/kg)
Monotherapy of ivermectin ( 200 µg/kg using 3 mg tablets) administered orally at day 0 Other names: Stromectol®
Drug: ivermectin (200 µg/kg)
Monotherapy of ivermectin ((200 µg/kg), 3 mg tablet) administered orally at day 0
Other Names:
  • Stromectol®
Active Comparator: E: moxidectin (8 mg)
Monotherapy of moxidectin (8 mg using 2 mg tablets) administered orally at day 0
Drug: moxidectin (8 mg)
Monotherapy of moxidectin (8 mg, using 2 mg tablets) administered orally at day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Egg reduction rate against T. trichiura
Time Frame: 14-21 day post-treatment
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.
14-21 day post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Superiority in terms of cure rates (CRs)
Time Frame: 14-21 day post-treatment
Assessment of superiority in terms of CRs of the drug combinations compared to their corresponding monotherapies: Arm C: Albendazole (400 mg) Arm D: Ivermectin (200 μg/kg) and Arm E: Moxidectin (8 mg)
14-21 day post-treatment
CRs against T. trichiura
Time Frame: 14-21 day post-treatment
CRs of each treatment will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
14-21 day post-treatment
Safety and tolerability
Time Frame: treatment until 3 months post-treatment
The observation time for AE starts when the treatment is initiated. Subjects will be kept for observation for at least 3 hours following treatment for any acute AE and. If there is any abnormal finding, the local study physician will perform a full clinical examination and findings will be recorded. An emergency kit will be available on site to treat any medical conditions that warrant urgent medical intervention. Participants will also be interviewed at 3h and 24h as well as retrospectively 14 -21 days, 5-6 weeks and 3 months after treatment about the occurrence of AEs.
treatment until 3 months post-treatment
Cure rates and egg reduction rates against concomitant soil-transmitted helminth infections
Time Frame: 14-21 days post-treatment

CRs and ERR will be calculated for Ascaris lumbricoides and hookworm infections.

CRs of each treatment will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.
14-21 days post-treatment
Extended effects on follow-up helminth prevalence
Time Frame: 5-6 weeks and 3 months post-treatment
CRs and ERR will be calculated for T. trichiura, A. lumbricoides and hookworm infections.
5-6 weeks and 3 months post-treatment
Diagnostic performance
Time Frame: baseline and 14-21 days post-treatment
Comparison of CRs based on egg counts retrieved from novel diagnostic tools (FECPAK-G2 and/or PCR) compared to standard microscopy (Kato-Katz method)
baseline and 14-21 days post-treatment
Pharmacokinetics and drug-drug interactions
Time Frame: between 0 and 72 hours
Characterization of 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
between 0 and 72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jennifer Keiser

Collaborators

Public Health Laboratory Ivo de Carneri

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Actual)

August 18, 2021

Study Completion (Actual)

September 22, 2021

Study Registration Dates

First Submitted

January 6, 2021

First Submitted That Met QC Criteria

January 6, 2021

First Posted (Actual)

January 7, 2021

Study Record Updates

Last Update Posted (Actual)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 31, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Moxi-ALB_IVM-ALB_combi-trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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