- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04056325
Efficacy, Safety, and PK of Ascending Dosages of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis (StrongMoxi)
Efficacy, Safety and Pharmacokinetics of Ascending Dosages of Moxidectin Alone and in Comparison to Ivermectin Against Strongyloides Stercoralis in Adults: a Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase 2a single-blinded and a phase 2b double-blinded randomized clinical trial, which aims to determine efficacy and safety of (2a) seven ascending oral moxidectin dosages in 210 adults infected with S. stercoralis, namely placebo, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg in Lao and (2b) the recommended dose moxidectin (i.e. the most promising dosage identified in trial A; between 2-12 mg) in comparison to the standard treatment dose of ivermectin (200 µg/kg) in 245 adults infected with S. stercoralis in Lao and Cambodia. Embedded in the trial is a pharmacokinetic/-dynamic study with the goal to measure moxidectin disposition in adults and to determine population pharmacokinetic (PK) parameters of the optimal dose of moxidectin in the treatment of S. stercoralis.
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Phnom Penh, Cambodia
- National Centre for Parasitology, Entomology and Malaria Control
-
-
-
-
-
Vientiane, Lao People's Democratic Republic
- National Institute of Public Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adults (≥ 18 years) infected with S. stercoralis
- Absence of major systemic illnesses
- Written informed consent signed by individual
Exclusion Criteria:
- Any abnormal medical conditions or chronic disease
- 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)
Study Plan
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: Phase 2a - Arm A
2 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Experimental: Phase 2a - Arm B
4 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Experimental: Phase 2a - Arm C
6 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Experimental: Phase 2a - Arm D
8 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Experimental: Phase 2a - Arm E
10 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Experimental: Phase 2a - Arm F
12 mg Moxidectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Placebo Comparator: Phase 2a - Arm G
matching Placebo tablet(s) at day 0 administered orally
|
Monotherapy, oral administration, single dose, matching number of tablets
|
Experimental: Phase 2b - Arm A
the recommended dose moxidectin (i.e. the most promising dosage identified in trial A; between 2-12 mg) at day 0 administered orally
|
Monotherapy, oral administration, single dose, fixed dose
|
Active Comparator: Phase 2b - Arm B
200 µg/kg ivermectin at day 0 administered orally
|
Monotherapy, oral administration, single dose, weight dependent
|
Placebo Comparator: Phase 2b - Arm P
matching Placebo tablet(s) at day 0 administered orally
|
Monotherapy, oral administration, single dose, matching number of tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cure rate against Strongyloidiasis stercoralis
Time Frame: 14-21 days after treatment
|
The conversion from being larvae positive pre-treatment to larvae negative post-treatment, or cure rate (CR).
|
14-21 days after treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Larvae-reduction rate (LRR) against Strongyloidiasis stercoralis
Time Frame: 14-21 days 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)
|
14-21 days after treatment
|
CRs and LRRs against concomitant soil-transmitted helminth infections
Time Frame: 14-21 days after treatment
|
CRs and LRRs will be calculated for T. trichiura, A. lumbricoides and hookworm infections as described in primary and secondary outcome.
|
14-21 days after treatment
|
Number of participants reporting adverse events
Time Frame: 14-21 days after treatment
|
Subjects will be kept for observation for at least 3 hours following treatment for any acute AEs.
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 3 weeks after treatment about the occurrence of AEs.
A standardized symptom questionnaire is used, that includes the recording of headache, abdominal pain, itching, nausea, vomiting, diarrhea, allergic reaction as well as any further mentioned event by the participant.
|
14-21 days after treatment
|
Maximum concentration (Cmax) of moxidectin in adults
Time Frame: 0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
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.
|
0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
Time to reach Cmax (tmax) of moxidectin in adults
Time Frame: 0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
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.
|
0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
Area under the curve (AUC) of moxidectin in adults
Time Frame: 0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
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.
|
0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
Elimination half life (t1/2) of moxidectin in adults
Time Frame: 0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
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.
|
0, 2, 4, 8, 24, and 72 hours, 7 and 21 days post treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jennifer Jennifer, Prof. Dr., STPH
Publications and helpful links
General Publications
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Strongyloides Stercoralis Infection
-
Jennifer KeiserNational Centre for Parasitology, Entomology and Malaria Control, CambodiaCompletedStrongyloides Stercoralis InfectionCambodia
-
Swiss Tropical & Public Health InstituteNational Institute of Public Health, Vientiane, LaosNot yet recruitingStrongyloidiasis | Strongyloides Stercoralis Infection
-
Universidad Nacional de SaltaAlbert B. Sabin Vaccine Institute; Fundacion Mundo SanoUnknownHelminthiasis | Strongyloides Stercoralis InfectionArgentina
-
IRCCS Sacro Cuore Don Calabria di NegrarCompletedStrongyloides Stercoralis InfectionItaly
-
IRCCS Sacro Cuore Don Calabria di NegrarWorld Health Organization; Universidad Central del Ecuador; CECOMET (Centro de...CompletedStrongyloidiasis | Strongyloides Stercoralis InfectionEcuador
-
Albert Einstein College of MedicineTerminatedStrongyloidiasis | Strongyloides Stercoralis InfectionUnited States
-
IRCCS Sacro Cuore Don Calabria di NegrarNot yet recruitingStrongyloides Stercoralis InfectionItaly
-
National Institute of Allergy and Infectious Diseases...RecruitingMalaria | Intestinal Worms | GI Protozoa | Echiniococcus | StrongyloidesUnited States
-
Radboud University Medical CenterSint MaartenskliniekActive, not recruitingSurgical Site Infection | Joint Infection | Infection, Surgical Site | Infection Prosthesis Hip and Knee | Infection, Prosthesis Related | Infection ProNetherlands
-
West Virginia UniversityEnrolling by invitationSkin and Soft Tissue Infection | Gastrointestinal Infection | Pulmonary Infection | Bone and Joint Infection | Endovascular Infection | Genitourinary InfectionUnited States
Clinical Trials on Moxidectin
-
Medicines Development for Global HealthWorld Health OrganizationCompleted
-
Swiss Tropical & Public Health InstitutePublic Health Laboratory Ivo de CarneriCompletedTrichuris Trichiura; InfectionTanzania
-
PfizerWorld Health OrganizationWithdrawnOnchocerciasis
-
Wyeth is now a wholly owned subsidiary of PfizerCompleted
-
Jennifer KeiserNational Centre for Parasitology, Entomology and Malaria Control, CambodiaCompletedStrongyloides Stercoralis InfectionCambodia
-
Medicines Development for Global HealthCompleted
-
Medicines Development for Global HealthRecruiting
-
Center for Research on Filariasis and Other Tropical...Active, not recruitingOnchocerciasis, Ocular | LoiasisCameroon
-
Washington University School of MedicineNational Public Health Institute of LiberiaNot yet recruitingOnchocerciasis | Onchocerciasis, Ocular | Tropical Disease | Onchocercal Subcutaneous Nodule | Onchocerca InfectionLiberia
-
Medicines Development for Global HealthCompleted