Efficacy, Safety, and PK of Ascending Dosages of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
NCT ID: NCT04056325
Last Updated: 2024-12-09
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2/PHASE3
617 participants
INTERVENTIONAL
2019-11-27
2021-04-30
Brief Summary
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Detailed Description
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The primary objective is to determine the dose-response of moxidectin based on cure rates (CR) against S. stercoralis and to quantify the efficacy of the recommended dose to the standard treatment (ivermectin) in adults.
The secondary objectives of the trial are: Evaluation of the safety and tolerability of the dose-dependent treatment regimes, evaluation of the safety and tolerability of moxidectin compared to ivermectin, comparison of the larvae reduction rate (LRR) of the different treatment regimens against S. stercoralis (trial 2a,b), determination of an exposure- (including Cmax, area under curve (AUC) and tmax) -response correlation of moxidectin in adults, comparison of the exposure-response of moxidectin using venous and capillary blood, evaluation of the cure rate of the different moxidectin treatment regimens against co-infection and the determination of the population PK parameters of the optimal dose of moxidectin in the treatment of S. stercoralis.
After obtaining informed consent from each individual, 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 collection and analysis by a quantitative Baermann method (in duplicates) of three stool samples. Randomization of participants into the different treatment arms will be stratified according to intensity of infection. The adults will also be interviewed before treatment, 3 and 24 hours as well as 21 days after treatment about the occurrence of adverse events (AE). The efficacy of the treatment will be determined 21 days post-treatment by collecting another three stool samples. All stool samples will be examined with duplicate Baermann assays recorded quantitatively. Co-infection with T. trichiura, A. lumbricoides and hookworm infection will be identified using duplicate Kato-Katz thick smears on stool samples.
A subsample of adults will further be sampled using finger pricking for micro sampling at 0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment to evaluate pharmacokinetic parameters (trial phase 2a) and at defined time windows, that are based on the PK model earned from trial 2a (trial phase 2b). For validation of the analytical method the subsample of one study arm (8 mg, trial phase 2a) will undergo venous blood sampling in addition to finger pricking.
An available case analysis (full analysis set according to the intention to treat principle) will be performed, including all subjects with primary end point data. Supplementary, a per-protocol analysis will be conducted. CRs will be calculated as the percentage of larvae-positive subjects at baseline who become larvae-negative after treatment. Larvae per gram (LPG) stool sample will be assessed by calculating the mean of the larvae counts from the three duplicate Baermann assays and divided by the mean weighted amount of these stool samples. The LRR will be calculated following: (LRR = (1-(mean at follow-up/mean at baseline))\*100) Geometric and arithmetic mean larvae counts will be calculated for the different treatment arms before and after treatment to assess the corresponding LRRs. Bootstrap resampling method with 2,000 replicates will be used to calculate 95% confidence intervals (CIs) for LRRs. Emax models using the dose finding package of the statistical software environment R will be implemented to predict the dose-response curves in terms of CRs and LRRs.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Phase 2a - Arm A
2 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm B
4 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm C
6 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm D
8 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm E
10 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm F
12 mg Moxidectin at day 0 administered orally
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2a - Arm G
matching Placebo tablet(s) at day 0 administered orally
Placebo oral tablet
Monotherapy, oral administration, single dose, matching number of tablets
Phase 2b - Arm A
the recommended dose moxidectin (i.e. the most promising dosage identified in phase 2a; between 2-12 mg) at day 0 administered orally
\+ Ivermectin placebo, corresponding to Phase 2b - Arm B
Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Phase 2b - Arm B
200 µg/kg ivermectin at day 0 administered orally
\+ Moxidectin placebo, corresponding to Phase 2b - Arm A
Ivermectin
Monotherapy, oral administration, single dose, weight dependent
Interventions
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Moxidectin
Monotherapy, oral administration, single dose, fixed dose
Ivermectin
Monotherapy, oral administration, single dose, weight dependent
Placebo oral tablet
Monotherapy, oral administration, single dose, matching number of tablets
Eligibility Criteria
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Inclusion Criteria
* Absence of major systemic illnesses
* Written informed consent signed by individual
Exclusion Criteria
* Negative diagnostic result for S. stercoralis
* No written informed consent by individual.
* Pregnant and lactating women.
* Recent use of anthelmintic drug (within past 4 weeks), attending other clinical trials during the study
* Known allergy to study medications (i.e. moxidectin, ivermectin)
* Currently taking medications with known interaction (i.e. for warfarin)
18 Years
60 Years
ALL
No
Sponsors
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National Institute of Public Health, Vientiane, Laos
OTHER
Jennifer Keiser
OTHER
Responsible Party
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Jennifer Keiser
Prof. Jennifer Keiser, PhD
Principal Investigators
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Jennifer Keiser, Prof. Dr.
Role: PRINCIPAL_INVESTIGATOR
Swiss TPH
Locations
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National Institute of Public Health
Vientiane, , Laos
Countries
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References
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Sprecher VP, Hofmann D, Savathdy V, Xayavong P, Norkhankhame C, Huy R, Khieu V, Sayasone S, Hattendorf J, Keiser J. Efficacy and safety of moxidectin compared with ivermectin against Strongyloides stercoralis infection in adults in Laos and Cambodia: a randomised, double-blind, non-inferiority, phase 2b/3 trial. Lancet Infect Dis. 2024 Feb;24(2):196-205. doi: 10.1016/S1473-3099(23)00507-8. Epub 2023 Nov 7.
Smit C, Hofmann D, Sayasone S, Keiser J, Pfister M. Characterization of the Population Pharmacokinetics of Moxidectin in Adults Infected with Strongyloides Stercoralis: Support for a Fixed-Dose Treatment Regimen. Clin Pharmacokinet. 2022 Jan;61(1):123-132. doi: 10.1007/s40262-021-01048-4. Epub 2021 Jul 23.
Hofmann D, Sayasone S, Sengngam K, Chongvilay B, Hattendorf J, Keiser J. Efficacy and safety of ascending doses of moxidectin against Strongyloides stercoralis infections in adults: a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial. Lancet Infect Dis. 2021 Aug;21(8):1151-1160. doi: 10.1016/S1473-3099(20)30691-5. Epub 2021 Mar 30.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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3
Identifier Type: -
Identifier Source: org_study_id