Efficacy and Safety of Moxidectin-Albendazole Co-administration in SAC

Efficacy and Safety of Moxidectin-albendazole Combination for Trichuris Trichiura Infections in School-aged Children: a Double-blind Randomised Controlled Superiority Trial

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06188715

Acronym

Moxiped

Enrollment

224

Registered

2024-01-03

Start date

2024-05-14

Completion date

2024-08-05

Last updated

2025-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ascariasis, Hookworm Infections, Trichuriasis

Keywords

Moxidectin, Albendazole, Anthelminthics, Trichuris trichiura, Ascaris lumbricoides, Hookworm, Whipworm, Soil-transmitted helminths

Brief summary

Detailed description

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 compared to albendazole monotherapy in school-aged children (SAC; aged 6-12 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, evidence on the safety profile of moxidectin-albendazole combination in this age group will be substantiated using a placebo (and albendazole) only arm. To date, this has only been established in adolescents (aged 16-18 years), who might present different symptoms or symptom severity compared with SAC. The primary objective of the trial is to comparatively assess the efficacy in terms of cure rate (CR) against T. trichiura infections among SAC receiving moxidectin/albendazole combination therapy and albendazole monotherapy. The secondary objectives of the trial are to compare the egg reduction rates (ERRs) of the treatment regimens against T. trichiura, 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 of moxidectin in T. trichiura infected SAC. After obtaining informed consent from 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 six treatment arms will be stratified according to intensity of infection and age. All participants will be interviewed before treatment, and at 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 participants 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. Adverse events will be compiled into frequency tables and compared between treatment groups using descriptive summary statistics.

Interventions

DRUGMoxidectin 2 mg Oral Tablet

Tablets of 2 mg moxidectin

DRUGAlbendazole 400 mg Oral Tablet

Tablets of 400 mg albendazole

DRUGPlacebo Moxidectin

Placebo tablets for moxidectin

DRUGPlacebo Albendazole

Placebo tablets for albendazole

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

The trial will be double blinded (i.e. study participants and the trial team/researchers conducting the treatment and assessing the outcomes will be blinded) using appearance-matching placebos.

Eligibility

Sex/Gender

ALL

Age

6 Years to 12 Years

Healthy volunteers

Inclusion criteria

* individuals aged 6-12 years (confirmed by birth certificate or similar document) * having given written informed consent signed by parents/caregivers * being able and willing to provide two stool samples at baseline and at follow-up assessment (14-21 days) * having at least two out of four Kato-Katz slides positive for T. trichiura at baseline * being able and willing to be examined by a study physician before and after treatment

Exclusion criteria

* presence or signs of major systemic illness, e.g. fever (temporal body temperature of \>38.0°C), severe anaemia (haemoglobin level of \<80 g/l) * history of severe acute disease or unmanaged, severe chronic disease (i.e., condition is not as therapeutically controlled as necessary) * use of anthelminthic drugs during study period * known allergy to study medication (i.e., moxidectin or albendazole) * being prescribed or taking concomitantly medication with known contraindications or drug interactions with the study medication * pregnancy (female participants aged 10-12 years) * concurrent participation in other clinical trials

Design outcomes

Primary

Measure	Time frame	Description
Cure Rate (CR) Against T. Trichiura	14-21 days post-treatment	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.

Secondary

Measure	Time frame	Description
Egg Reduction Rate (ERR) Against T. Trichiura (Geometric Mean ERR)	14-21 days post-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.
Egg Reduction Rate (ERR) Against T. Trichiura (Arithmetic Mean ERR)	14-21 days post-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.
Cure Rate (CR) Against A. Lumbricoides	14-21 days post-treatment	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
Egg Reduction Rate (ERR) Against A. Lumbricoides (Geometric Mean ERR)	14-21 days post-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.
Cure Rate (CR) Against Hookworm	14-21 days post-treatment	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
Egg Reduction Rate (ERR) Against Hookworm (Geometric Mean ERR)	14-21 days post-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.
Egg Reduction Rate (ERR) Against Hookworm (Arithmetic Mean ERR)	14-21 days post-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.
Number of Participants Reporting Adverse Events (AEs)	3 hours, 24 hours and 14-21 days post-treatment	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.
Egg Reduction Rate (ERR) Against A. Lumbricoides (Arithmetic Mean ERR)	14-21 days post-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.

Other

Measure	Time frame	Description
Blood Concentration of Moxidectin	0 to 24 hours post-treatment	For characterization of population pharmacokinetics (PK), moxidectin concentration 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.

Countries

Tanzania

Participant flow

Participants by arm

Arm	Count
Arm A: Moxidectin 4/8 mg & Albendazole Combination therapy of moxidectin (4 mg or 8 mg, i.e. 2 or 4 tablets of 2 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0 Moxidectin 2 mg Oral Tablet: Tablets of 2 mg moxidectin Albendazole 400 mg Oral Tablet: Tablets of 400 mg albendazole	114
Arm B: Albendazole Placebo for moxidectin (2 or 4 tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0 Albendazole 400 mg Oral Tablet: Tablets of 400 mg albendazole Placebo Moxidectin: Placebo tablets for moxidectin	74
Arm C: Placebo Placebo for moxidectin (2 or 4 tablets) and placebo for albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0 Placebo Moxidectin: Placebo tablets for moxidectin Placebo Albendazole: Placebo tablets for albendazole	36
Total	224

Baseline characteristics

Characteristic	Arm A: Moxidectin 4/8 mg & Albendazole	Arm B: Albendazole	Arm C: Placebo	Total
Age, Continuous	8.0 years STANDARD_DEVIATION 1.2	8.0 years STANDARD_DEVIATION 1.4	7.9 years STANDARD_DEVIATION 1.2	8.0 years STANDARD_DEVIATION 1.3
Ascaris lumbricoides co-infection	38 Participants	18 Participants	11 Participants	67 Participants
Hookworm co-infection	53 Participants	27 Participants	14 Participants	94 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants
Region of Enrollment Tanzania	114 participants	74 participants	36 participants	224 participants
Sex: Female, Male Female	46 Participants	34 Participants	15 Participants	95 Participants
Sex: Female, Male Male	68 Participants	40 Participants	21 Participants	129 Participants
Trichuris trichiura infection intensity Heavy infection (>9999 EPG)	1 Participants	0 Participants	1 Participants	2 Participants
Trichuris trichiura infection intensity Light infection (<1000 EPG)	86 Participants	56 Participants	27 Participants	169 Participants
Trichuris trichiura infection intensity Moderate infection (1000-9999 EPG)	27 Participants	18 Participants	8 Participants	53 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 114	0 / 74	0 / 36
other Total, other adverse events	10 / 114	3 / 74	3 / 36
serious Total, serious adverse events	0 / 114	0 / 74	0 / 36

Outcome results

Primary

Cure Rate (CR) 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.