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Efficacy and Safety of MOX/ALB Co-administration

Primary Purpose

Trichuriasis, Ascariasis, Hookworm Infections

Status
Completed
Phase
Phase 3
Locations
Côte D'Ivoire
Study Type
Interventional
Intervention
Moxidectin 2 mg Oral Tablet
Albendazole 400 mg Oral Tablet
Ivermectin 3 mg Oral Tablet
Sponsored by
Jennifer Keiser
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Trichuriasis focused on measuring Albendazole, Moxidectin, Ivermectin, Anthelmintics, T. trichiura, A. lumbricoides, Hookworm, Whipworm, Soil-transmitted helminths

Eligibility Criteria

12 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged between 12 and 60 years
  • Written informed consent signed by either parents/caregivers for underage adolescents (aged 12-17 years) or by the participant him/herself (18-60 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 at follow-up assessment 14-21 days 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:

  • 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
  • Known or suspected infection with Loa loa
  • History of acute or severe chronic disease
  • Abnormal liver function assessed by multiple biochemical blood-based analyses
  • 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 3 months
  • Known allergy to study medications (i.e. albendazole, ivermectin or moxidectin)
  • Taking medication with known contraindication to or interaction with study drugs

Sites / Locations

  • Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Arm A: moxidectin and albendazole

Arm B: albendazole

Arm C: ivermectin and albendazole

Arm Description

Combination therapy of moxidectin (8 mg, i.e. 4 tablets of 2 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0

Placebo (for moxidectin, 4 tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0

Combination therapy of ivermectin (Stromectol®, 200 µg/kg using tablets of 3 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0

Outcomes

Primary Outcome Measures

Cure Rate (CR) of Moxidectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.

Secondary Outcome Measures

Egg Reduction Rate (ERR) of Moxidectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
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.
Cure Rate (CR) of Ivermectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Egg Reduction Rate (ERR) of Ivermectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
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.
Cure Rates (CRs) of the Study Drugs Against Ascaris Lumbricoides Infections in Co-infected Participants
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Egg Reduction Rates (ERRs) of the Study Drugs Against Ascaris Lumbricoides Infections in Co-infected Participants
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 three treatment arms before and after treatment to assess the corresponding ERRs.
Cure Rates (CRs) of the Study Drugs Against Hookworm Infections in Co-infected Participants
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Egg Reduction Rates (ERRs) of the Study Drugs Against Hookworm Infections in Co-infected Participants
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 three treatment arms before and after treatment to assess the corresponding ERRs.
Adverse Events (AEs)
Participants will be monitored at the site for 3 hours following treatment for any acute AEs and reassessment will be done at 24h post-treatment. In addition, participants will be interviewed 3 and 24 hours after treatment and retrospectively at days 14-21 about the occurrence of AEs.

Full Information

First Posted
January 18, 2021
Last Updated
January 16, 2023
Sponsor
Jennifer Keiser
Collaborators
Centre Suisse de Recherches Scientifiques en Cote d'Ivoire
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1. Study Identification

Unique Protocol Identification Number
NCT04726969
Brief Title
Efficacy and Safety of MOX/ALB Co-administration
Official Title
Efficacy and Safety of Combination Moxidectin and Albendazole, Ivermectin and Albendazole and Albendazole Alone in Adolescents and Adults Infected With Trichuris Trichiura: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
September 9, 2021 (Actual)
Study Completion Date
September 9, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jennifer Keiser
Collaborators
Centre Suisse de Recherches Scientifiques en Cote d'Ivoire

4. Oversight

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

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trichuriasis, Ascariasis, Hookworm Infections
Keywords
Albendazole, Moxidectin, Ivermectin, Anthelmintics, T. trichiura, A. lumbricoides, Hookworm, Whipworm, Soil-transmitted helminths

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The parallel group trial co-administered moxidectin/albendazole versus albendazole alone will be double blinded (i.e. study participants and the trial team/researchers conducting the treatment and assessing the outcomes will be blinded) using tablets including appearance-matched placebos, while the ivermectin/albendazole arm will be open label due to the nature of ivermectin (i.e. requiring bodyweight-dependent doses).
Allocation
Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: moxidectin and albendazole
Arm Type
Experimental
Arm Description
Combination therapy of moxidectin (8 mg, i.e. 4 tablets of 2 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Arm Title
Arm B: albendazole
Arm Type
Placebo Comparator
Arm Description
Placebo (for moxidectin, 4 tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Arm Title
Arm C: ivermectin and albendazole
Arm Type
Experimental
Arm Description
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using tablets of 3 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Intervention Type
Drug
Intervention Name(s)
Moxidectin 2 mg Oral Tablet
Intervention Description
Tablets of 2 mg moxidectin
Intervention Type
Drug
Intervention Name(s)
Albendazole 400 mg Oral Tablet
Other Intervention Name(s)
Zentel®
Intervention Description
Tablets of 400 mg albendazole
Intervention Type
Drug
Intervention Name(s)
Ivermectin 3 mg Oral Tablet
Other Intervention Name(s)
Stromectol®
Intervention Description
Tablets of 3 mg ivermectin
Primary Outcome Measure Information:
Title
Cure Rate (CR) of Moxidectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
Description
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Time Frame
14-21 days after treatment
Secondary Outcome Measure Information:
Title
Egg Reduction Rate (ERR) of Moxidectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
Description
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.
Time Frame
14-21 days after treatment
Title
Cure Rate (CR) of Ivermectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
Description
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Time Frame
14-21 days after treatment
Title
Egg Reduction Rate (ERR) of Ivermectin/Albendazole Combination Therapy Compared to Albendazole Monotherapy Against T. Trichiura
Description
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.
Time Frame
14-21 days after treatment
Title
Cure Rates (CRs) of the Study Drugs Against Ascaris Lumbricoides Infections in Co-infected Participants
Description
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Time Frame
14-21 days after treatment
Title
Egg Reduction Rates (ERRs) of the Study Drugs Against Ascaris Lumbricoides Infections in Co-infected Participants
Description
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 three treatment arms before and after treatment to assess the corresponding ERRs.
Time Frame
14-21 days after treatment
Title
Cure Rates (CRs) of the Study Drugs Against Hookworm Infections in Co-infected Participants
Description
The CR will be calculated as the proportion of participants converting from being egg positive pre-treatment to egg negative post-treatment, multiplied by 100.
Time Frame
14-21 days after treatment
Title
Egg Reduction Rates (ERRs) of the Study Drugs Against Hookworm Infections in Co-infected Participants
Description
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 three treatment arms before and after treatment to assess the corresponding ERRs.
Time Frame
14-21 days after treatment
Title
Adverse Events (AEs)
Description
Participants will be monitored at the site for 3 hours following treatment for any acute AEs and reassessment will be done at 24h post-treatment. In addition, participants will be interviewed 3 and 24 hours after treatment and retrospectively at days 14-21 about the occurrence of AEs.
Time Frame
3 hours, 24 hours and 14-21 days after treatment
Other Pre-specified Outcome Measures:
Title
Concentrations of Albendazole and Ivermectin/Albendazole Combination in Adolescents (Aged 12 to 20 Years)
Description
For characterization of population pharmacokinetics (PK) and drug-drug interaction parameters ivermectin, albendazole and its metabolites will be quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a lower limit of quantification of 1-5 ng/ml.
Time Frame
0 to 24 hours after treatment
Title
Genetic Variants in Ivermectin/Albendazole Participants
Description
In case of unexpected results for outcome measure 10 (Concentrations of Albendazole and Ivermectin/Albendazole Combination in Adolescents (Aged 12 to 20 Years)), whole genome sequencing will be performed on blood samples from participants in the ivermectin/albendazole arm to analyse genetic variation of relevance for ivermectin metabolism.
Time Frame
before treatment, i.e. at enrolment
Title
Gut Bacterial Communities in Stool Samples
Description
Taxonomic relative abundances of gut bacterial communities will be analysed with high-throughput sequencing. Absolute abundances of specific taxa will be measured using taxon-specific qPCR. Changes in relative and absolute abundances will be measured before and after treatment.
Time Frame
before treatment, i.e. at screening, and 14-21 days after treatment
Title
Exploratory Outcome: Number of Participants Within Each Blood Type Category (A, B, AB and 0)
Description
Blood type of participants will be collected during clinical examination prior treatment using blood type determination cards.
Time Frame
before treatment, i.e. at enrolment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged between 12 and 60 years Written informed consent signed by either parents/caregivers for underage adolescents (aged 12-17 years) or by the participant him/herself (18-60 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 at follow-up assessment 14-21 days 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: 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 Known or suspected infection with Loa loa History of acute or severe chronic disease Abnormal liver function assessed by multiple biochemical blood-based analyses 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 3 months Known allergy to study medications (i.e. albendazole, ivermectin or moxidectin) Taking medication with known contraindication to or interaction with study drugs
Facility Information:
Facility Name
Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)
City
Abidjan
Country
Côte D'Ivoire

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Efficacy and Safety of MOX/ALB Co-administration

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