Efficacy, Safety and PK of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis (StrongMoxi_KH)
Primary Purpose
Strongyloides Stercoralis Infection
Status
Completed
Phase
Phase 3
Locations
Cambodia
Study Type
Interventional
Intervention
Moxidectin 2 mg
Ivermectin 3 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Strongyloides Stercoralis Infection
Eligibility Criteria
Inclusion Criteria:
- Adults (18-65 years)
- Infected with S. stercoralis (positive)
- Absence of major systemic illnesses
- Written informed consent
Exclusion Criteria:
- Any abnormal medical conditions or chronic disease
- Negative diagnostic result for S. stercoralis
- No written informed consent by the individual.
- Pregnant and lactating women.
- Recent use of an 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)
Sites / Locations
- National Centre for Parasitology, Entomology and Malaria Control
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Moxidectin
Ivermectin
Arm Description
8 mg Moxidectin at day 0 administered orally
200 ug/kg Ivermectin at day 0 administered orally
Outcomes
Primary Outcome Measures
Cure rate against Strongyloides stercoralis
The conversion from being larvae positive pre-treatment to larvae negative post-treatment, or cure rate (CR).
Secondary Outcome Measures
Larvae-reduction rate (LRR) against Strongyloidiasis stercoralis
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)
CRs against concomitant soil-transmitted helminth infections
CRs will be calculated for T. trichiura, A. lumbricoides and hookworm infections as described in primary outcome.
Number of participants reporting adverse events
Subjects will be kept for observation for at least 3 hours following treatment for any acute adverse events. If there is any abnormal finding, the local study physician will perform a full clinical, physical and biochemical examination and findings will be recorded. An emergency kit will be available on-site to treat any medical conditions that warrant urgent medical intervention. In addition, patients will also be interviewed 3 and 24 hours and again at several points after treatment about the occurrence of adverse events. A standardized symptom questionnaire is used, that includes the recording of headache, abdominal pain, itching, nausea, vomiting, diarrhoea, allergic reaction as well as any further mentioned event by the participant.
Maximum concentration (Cmax) of moxidectin in adults, young adults and adults with a BMI <19
Upon oral intake moxidectin levels in blood will be quantified with time using a micro sampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The PK analysis will be undertaken fitting a structural compartmental PK model.
Time to reach Cmax (tmax) of moxidectin in adults, young adults and adults with a BMI <19
Upon oral intake moxidectin levels in blood will be quantified with time using a micro sampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The PK analysis will be undertaken fitting a structural compartmental PK model.
Area under the curve (AUC) of moxidectin in adults, young adults and adults with a BMI <19
Upon oral intake, moxidectin levels in the blood will be quantified with time using a microsampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The pharmacokinetic analysis will be undertaken fitting a structural compartmental PK model.
Elimination half life (t1/2) of moxidectin in adults, young adults and adults with a BMI <19
Upon oral intake, moxidectin levels in the blood will be quantified with time using a microsampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The pharmacokinetic analysis will be undertaken fitting a structural compartmental pharmacokinetic model.
Genetic profiling of S. stercoralis positive stool samples
From all S. stercoralis positive stool samples, the extracted larvae will be stored in 70% Ethanol after examination by Baermann. Samples will be shipped to the investigating laboratory (La Trobe University) at room temperature.
Socioeconomic characteristics (SES)
To all participating households, a brief questionnaire will be administered assessing information on socioeconomic characteristics (SES) and access to sanitation, water facilities, and hygiene behaviour.
Full Information
NCT ID
NCT04848688
First Posted
April 8, 2021
Last Updated
September 26, 2022
Sponsor
Jennifer Keiser
Collaborators
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
1. Study Identification
Unique Protocol Identification Number
NCT04848688
Brief Title
Efficacy, Safety and PK of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
Acronym
StrongMoxi_KH
Official Title
Efficacy, Safety and Pharmacokinetics of Moxidectin and Its Comparison to Ivermectin Against Strongyloides Stercoralis in Adults: a Randomized Controlled Non-inferiority Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
February 5, 2022 (Actual)
Primary Completion Date
July 17, 2022 (Actual)
Study Completion Date
July 17, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jennifer Keiser
Collaborators
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is an extension to the study StrongMoxi NCT04056325 and entails modifications based on the outcome of NCT04056325 part A.
The study is a phase 3, double-blinded and randomized clinical trial conducted in Cambodia. It aims at providing evidence on efficacy, safety and pharmacokinetic measures of 8 mg of moxidectin compared to 200 μg/kg ivermectin in adults infected with S. stercoralis. The efficacy of the treatment will be assessed by collecting three stool samples once per-treatment and once 21-28 days post-treatment. The stool samples will be analyzed by a quantitative duplicate Baermann assay.
Detailed Description
The study is a phase 3 trial and will determine the efficacy and safety of:
8 mg of moxidectin in comparison to the standard treatment dose of ivermectin (200 μg/kg) in adults infected with S. stercoralis and to measure moxidectin disposition in adults using a microsampling device.
Our primary objective is to demonstrate non-inferiority in terms of cure rate (CR) against S. stercoralis in adults of an oral 8 mg of moxidectin compared to 200 μg/kg of ivermectin.
The secondary objectives of the trial are:
to evaluate the safety and tolerability of moxidectin
to compare the larval reduction rate (LRR) of the two different treatment groups against S. stercoralis
to evaluate the CRs and egg reduction rates (ERRs) of the different treatment drugs and regimens against soil-transmitted helminths (STH) co-infections.
to determine the population pharmacokinetics (popPK) of moxidectin administered to S. stercoralis-infected in adolescents, as well as normal and underweight adults.
to investigate potential extended effects on follow-up helminth prevalence at 42-49 and 63-70 days post-treatment
to relate socioeconomic characteristics (SES), access to sanitation, water facilities, hygiene to baseline infection intensity.
to determine the larval excretion pattern till day 70 in the moxidectin treatment arm, determined at every second day between day zero and 70 post-treatment in a subset of 50 adults.
to determine the origin of the remaining worm burden after treatment to treatment failure and reinfection based on genetic profiling.
Three stool samples will be collected at baseline analysed in duplicates by a quantitative Baermann method for S. stercoralis infection. Co-infection with other Helminths species will be identified using duplicate Kato-Katz thick smears on two stool samples. The medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical and physical examination carried out by the study physician shortly before the treatment day. Each participant will be asked to provide a finger-prick blood sample for haemoglobin measurements at baseline. Enrolled participants will be treated with either 8 mg of moxidectin or with the standard treatment ivermectin (200 μg/kg). The adults will be interviewed a) before treatment, 3 and 24 hours as well as 21-28, 42-49 and 63-70 days after treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 21-28 days of post-treatment. All stool samples will be examined with quantitative sixtuplicate Baermann assays and quadruplet Kato-Katz thick smears. At 42-49 and 63-70 days post-treatment another three stool samples will be collected and quantified for S. stercoralis larvae using Baermann assay to assess potential long-term benefits of the study drugs and treatment regimen. Of 50 adults in the moxidectin arm only, additional stool samples will be collected every second day between treatment and 70 days post treatment to evaluate larval secretion patterns.
To determine the PK parameters of the study drug, a subsample of 10 willing youngest adults (aged 18~20 years old) and voluntary 20 adults (aged 18-65) in the moxidectin arm will further be asked to provide 3 finger pricks of blood per participant. The finger pricks will be collected within three consecutive days of post-treatment application. Not more than two finger pricks will be taken on the same day. To all participating households, a brief questionnaire will be administered assessing information on socioeconomic characteristics (SES) and access to sanitation, water facilities, and hygiene behaviour.
An available case analysis (full analysis set according to the intention to treat principle) will be performed, including all participants with primary endpoint data.
CRs will be calculated as the percentage of larvae-positive subjects at baseline who become larvae-negative after treatment, assessed 21-28 days post-treatment by sextuplicate Baermann. Uncertainty estimates around the differences among CRs will be assessed using melded confidence intervals with mid-p correction. The non-inferiority.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Strongyloides Stercoralis Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Parallel study with 2 treatment arms
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded (Participant and Care provider) Additionally, the principal investigator and the statistician will be blinded.
PK substudy is single-blinded (Participant)
Allocation
Randomized
Enrollment
332 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Moxidectin
Arm Type
Experimental
Arm Description
8 mg Moxidectin at day 0 administered orally
Arm Title
Ivermectin
Arm Type
Experimental
Arm Description
200 ug/kg Ivermectin at day 0 administered orally
Intervention Type
Drug
Intervention Name(s)
Moxidectin 2 mg
Intervention Description
Monotherapy, oral administration, single-dose, fixed-dose, 4 tablets a 2 mg to yield an 8 mg final dose.
Intervention Type
Drug
Intervention Name(s)
Ivermectin 3 mg
Intervention Description
Monotherapy, oral administration, single-dose, weight dependent, The number of tablets will be adjusted according to the patients' weight to yield 200 ug/kg final dose.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Monotherapy, oral administration, single dose, matching number of tablets to either moxidectin or ivermectin
Primary Outcome Measure Information:
Title
Cure rate against Strongyloides stercoralis
Description
The conversion from being larvae positive pre-treatment to larvae negative post-treatment, or cure rate (CR).
Time Frame
21-28 days after treatment
Secondary Outcome Measure Information:
Title
Larvae-reduction rate (LRR) against Strongyloidiasis stercoralis
Description
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)
Time Frame
21-28, 42-49 and 63-70 days after treatment (All) or every second day between day 0 and day 70 (Arm Moxidectin, n=50)
Title
CRs against concomitant soil-transmitted helminth infections
Description
CRs will be calculated for T. trichiura, A. lumbricoides and hookworm infections as described in primary outcome.
Time Frame
21-28 days after treatment
Title
Number of participants reporting adverse events
Description
Subjects will be kept for observation for at least 3 hours following treatment for any acute adverse events. If there is any abnormal finding, the local study physician will perform a full clinical, physical and biochemical examination and findings will be recorded. An emergency kit will be available on-site to treat any medical conditions that warrant urgent medical intervention. In addition, patients will also be interviewed 3 and 24 hours and again at several points after treatment about the occurrence of adverse events. A standardized symptom questionnaire is used, that includes the recording of headache, abdominal pain, itching, nausea, vomiting, diarrhoea, allergic reaction as well as any further mentioned event by the participant.
Time Frame
3 hours, 24 hours, 21-28 days, 42-49 days , 63-70 days after treatment
Title
Maximum concentration (Cmax) of moxidectin in adults, young adults and adults with a BMI <19
Description
Upon oral intake moxidectin levels in blood will be quantified with time using a micro sampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The PK analysis will be undertaken fitting a structural compartmental PK model.
Time Frame
0-24 hours after treatment
Title
Time to reach Cmax (tmax) of moxidectin in adults, young adults and adults with a BMI <19
Description
Upon oral intake moxidectin levels in blood will be quantified with time using a micro sampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The PK analysis will be undertaken fitting a structural compartmental PK model.
Time Frame
0-24 hours after treatment
Title
Area under the curve (AUC) of moxidectin in adults, young adults and adults with a BMI <19
Description
Upon oral intake, moxidectin levels in the blood will be quantified with time using a microsampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The pharmacokinetic analysis will be undertaken fitting a structural compartmental PK model.
Time Frame
0-24 hours after treatment
Title
Elimination half life (t1/2) of moxidectin in adults, young adults and adults with a BMI <19
Description
Upon oral intake, moxidectin levels in the blood will be quantified with time using a microsampling device. Moxidectin 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 foreseen limit of quantification of approximately 5 ng/ml. The pharmacokinetic analysis will be undertaken fitting a structural compartmental pharmacokinetic model.
Time Frame
0-24 hours after treatment
Title
Genetic profiling of S. stercoralis positive stool samples
Description
From all S. stercoralis positive stool samples, the extracted larvae will be stored in 70% Ethanol after examination by Baermann. Samples will be shipped to the investigating laboratory (La Trobe University) at room temperature.
Time Frame
Pre-treatment
Title
Socioeconomic characteristics (SES)
Description
To all participating households, a brief questionnaire will be administered assessing information on socioeconomic characteristics (SES) and access to sanitation, water facilities, and hygiene behaviour.
Time Frame
Pre-treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults (18-65 years)
Infected with S. stercoralis (positive)
Absence of major systemic illnesses
Written informed consent
Exclusion Criteria:
Any abnormal medical conditions or chronic disease
Negative diagnostic result for S. stercoralis
No written informed consent by the individual.
Pregnant and lactating women.
Recent use of an 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Keiser, Prof. Dr
Organizational Affiliation
STPH
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Centre for Parasitology, Entomology and Malaria Control
City
Phnom Penh
Country
Cambodia
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Efficacy, Safety and PK of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
We'll reach out to this number within 24 hrs