Clinical trial NCT04056325
Conditions: Strongyloides Stercoralis Infection
Sponsor: Jennifer Keiser
Start date: 2019-11-27; Completion date: 2021-04-30
Enrollment: 617 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is a phase 2, blinded and randomized clinical trial. The phase 2a trial is single blinded and conducted in Lao, while the phase 2b trial is double-blinded and conducted in Lao and Cambodia. The study aims at providing evidence on effective doses and safety of moxidectin in adults against infection with S. stercoralis in Laos (trial 2a) and efficacy and safety of moxidectin compared to ivermectin in adults against infection with S. stercoralis in Laos and Cambodia (trial 2b). The efficacy of the treatment will be assessed by collecting three stool samples once pre-treatment and once 21 days post-treatment. The stool samples will be analyzed by a quantitative Baermann assay.

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 350 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.

Arms: arm 1: 2 mg Moxidectin at day 0 administered orally arm 2: 4 mg Moxidectin at day 0 administered orally arm 3: 6 mg Moxidectin at day 0 administered orally arm 4: 8 mg Moxidectin at day 0 administered orally arm 5: 10 mg Moxidectin at day 0 administered orally arm 6: 12 mg Moxidectin at day 0 administered orally arm 7: matching Placebo tablet(s) at day 0 administered orally arm 8: 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 arm 9: 200 µg/kg ivermectin at day 0 administered orally

\+ Moxidectin placebo, corresponding to Phase 2b - Arm A
Interventions: intervention 1: Moxidectin intervention 2: Ivermectin intervention 3: Placebo oral tablet
Intervention descriptions: intervention 1: Monotherapy, oral administration, single dose, fixed dose intervention 2: Monotherapy, oral administration, single dose, weight dependent intervention 3: Monotherapy, oral administration, single dose, matching number of tablets

Protocol documents:
Prot_SAP_000.pdf: 
Efficacy, safety and pharmacokinetics of ascending dosages of 
moxidectin alone and in comparison to ivermectin against 
Strongyloides stercoralis infection in adults: a randomized 
controlled trial 
 
NCT Number: NCT04056325 
 
Document date: 01 July 2020 


StrongMoxi, Protocol, v2.2, 01.07.2020 
 
Page 1 of 45 
 
 
Study Protocol 
 
 
Efficacy, safety and pharmacokinetics of ascending dosages of moxidectin 
alone and in comparison to ivermectin against Strongyloides stercoralis 
infection in adults: a randomized controlled trial 
 
 
Protocol Number 
2 
Version Number 
V2.2 
Document Date 
01.07.2020 
Sponsor Contact 
Prof. Dr. Jennifer Keiser, Swiss Tropical and Public Health 
Institute, Tel.: +41 61 284-8218 
Fax: +41 61 284-8105 
E-mail: jennifer.keiser@unibas.ch 
Principal Investigator 
Prof. Dr. Jennifer Keiser, Swiss Tropical and Public Health 
Institute, Tel.: +41 61 284-8218 
Fax: +41 61 284-8105 
E-mail: jennifer.keiser@unibas.ch 
Funding Agency 
European Research Council (ERC), Fondazione Adiuvare 


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1. General Information 
 
I. 
List of investigators and other persons involved 
 
Title 
Names 
Institution 
Position 
Function in trial 
Prof. Dr. 
Jennifer Keiser 
Swiss Tropical and 
Public Health 
Institute (Swiss 
TPH) 
 
Unit head 
Principal 
investigator 
Dr. MD 
Somphou 
Sayasone 
Swiss Tropical and 
Public Health 
Institute, 
National Institute 
of Public Health, 
Vientiane, Laos 
Project 
leader, 
Physician 
Co-investigator, 
Physician 
Dr.  
Virak Khieu 
National Centre for 
Parasitology, 
Entomology and 
Malaria Control 
Phnom Penh, 
Cambodia 
Project 
leader, 
Physician 
Co-investigator, 
Physician 
Dr. 
Daniela 
Hofmann 
Swiss Tropical and 
Public Health 
Institute 
Postdoc 
Co-investigator 
Dr. 
Jan Hattendorf 
 
Swiss TPH  
 
Group leader 
Statistician 
 
 
 
 


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II. 
Signatures  
 
Statistician 
Signature 
 
 
 
 
Date of Signature  
01.07.2020 
Name  
Jan Hattendorf 
Title 
Dr. 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Socinstr. 57 
CH- 4002 Basel, Switzerland  
Phone 
+41 61 284-8193 
 
 
Principal investigator 
Signature 
 
 
 
 
 
Date of Signature  
01.07.2020 
Name  
Jennifer Keiser 
Title 
Prof. 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Socinstr. 57 
CH- 4002 Basel, Switzerland  
Phone 
+41 61 284-8218 
 
I have read this protocol and agree that it contains all necessary details for carrying out this 
trial. I will conduct the trial as outlined herein and will complete the trial within the time 
designated. I will provide copies of the protocol and all pertinent information to all individuals 
responsible to me who assist in the conduct of this trial. I will discuss this material with them 
to ensure they are fully informed regarding the drug and the conduct of the trial. 
I will use only the informed consent forms approved by the Sponsor or its representative and 
will fulfill all responsibilities for submitting pertinent information to the Independent Ethics 
Committees responsible for this trial. I agree that the Sponsor or its representatives shall have 
access to any source documents from which Case Report Form information may have been 
generated. 
 


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Co-investigator and Physician 
Signature 
 
Date of Signature  
01.07.2020 
Name  
Somphou Sayasone  
Title 
Dr. 
Institution 
Swiss Tropical and Public Health Institute / National Institute of Public Health, 
Vientiane, Laos 
Address 
Samsenthai Road,  
Kaognot village, Sisattanak district,  
Vientiane Capital Lao PDR, 
Phone 
+856 20 556 79 603 or +856-20-5567 9603 
 
Co-investigator 
Signature 
 
 
 
 
 
Date of Signature  
01.07.2020 
Name  
Virak Khieu  
Title 
Dr. 
Institution 
National Centre for Parasitology, Entomology and Malaria Control 
Phnom Penh, Cambodia 
Address 
#477 Betong Street, Village Trapangsvay, Sanakat  Phnom Penh Thmey, Khan 
Sen Sok, Phnom Penh  
Phone 
+(855)-12 677 244 
 
Co-investigator 
Signature 
 
Date of Signature  
01.07.2020 
Name  
Daniela Hofmann 
Title 
Dr. 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Socinstr. 57 
CH- 4002 Basel, Switzerland  
Phone 
+41 61 207 15 06 
 
 
 
 


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III. 
Table of contents 
 
1. General Information ........................................................................................................... 2 
2. Background information ....................................................................................................13 
3. Trial objective and purpose ...............................................................................................16 
4. Methodology .....................................................................................................................17 
4.1. Primary and secondary endpoint ................................................................................17 
4.2. Type of trial ................................................................................................................17 
4.3. Trial design ................................................................................................................17 
4.4. Measure to minimize bias ..........................................................................................22 
4.5. Study duration and duration of subject participation ...................................................23 
4.6. Schedule of visits .......................................................................................................23 
5. Selection of the trial subjects ............................................................................................23 
5.1. Recruitment ...............................................................................................................23 
5.2. Inclusion criteria .........................................................................................................24 
5.3. Criteria for discontinuation of trial ...............................................................................25 
5.4. Treatment of subjects.................................................................................................25 
5.5. Concomitant therapy ..................................................................................................26 
6. Assessment of safety .......................................................................................................27 
6.1. Adverse event definition .............................................................................................27 
6.2. Methods of recording and assessing adverse events .................................................30 
6.3. Reporting of serious adverse events ..........................................................................30 
6.4. Safety reporting to Health Authorities and Ethics Committees ....................................31 
7. Statistics ...........................................................................................................................31 
7.1. Definition of primary endpoint .....................................................................................31 
7.2. Justification of number of trial subject ........................................................................31 
7.3. Description of statistical methods ...............................................................................32 
8. Duties of the investigator ..................................................................................................33 
8.1. Investigator’s confirmation .........................................................................................33 
8.2. Damage coverage ......................................................................................................34 


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8.3. Project management ..................................................................................................34 
9. Ethical considerations .......................................................................................................34 
9.1. Independent Ethics Committee (IEC) .........................................................................34 
9.2. Evaluation of the risk-benefit ratio ..............................................................................35 
9.3. Subject information and consent ................................................................................35 
9.4. Subject confidentiality ................................................................................................35 
9.5. Subjects requiring particular protection ......................................................................36 
9.6. Other aspects ............................................................................................................36 
10. Data management ..........................................................................................................36 
10.1. Data collection .........................................................................................................36 
10.2. Data handling and definition of source data - data entered directly in the Case Report 
Form .................................................................................................................................37 
10.3. Definition of reference language – translation of study documents ...........................38 
10.4. Storage and preservation .........................................................................................38 
11. Quality control and quality assurance .............................................................................39 
11.1. Monitoring and auditing ............................................................................................39 
11.2. Data and safety monitoring board (WHO) / data monitoring committee (EU/FDA) ....39 
12. Dissemination of results and publication .........................................................................39 
13. References .....................................................................................................................40 
Appendix 1 ...........................................................................................................................43 
 


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IV. 
Synopsis 
Study Title 
Efficacy, safety and pharmacokinetics of ascending dosages of 
moxidectin alone and in comparison to ivermectin against 
Strongyloides stercoralis infection in adults: a randomized 
controlled trial 
Study Type 
Phase 2 trials – Phase 2a (trial A) & Phase 2b/3 (trial B) 
Sample size 
210 (trial A) and 350 (trial B) in two settings 
Indication 
Strongyloidiasis stercoralis infection (larvae in stool) 
Investigational Product 
and Reference 
Treatment 
Investigational product: moxidectin 
Reference treatment: ivermectin 
Protocol Number, Date 
and Version 
2, 01.07.2020, v2.2 
Trial registration 
Will be registered on (http://www.controlled-trials.com/) 
 
Study Rationale 
To provide evidence on: 
(A) Effective doses and safety of moxidectin in adults against 
infection with S. stercoralis in Laos (trial A: dose finding 
study). 
(B) Efficacy and safety of moxidectin compared to ivermectin 
in adults against infection with S. stercoralis in Laos and 
Cambodia (trial B: parallel group study). 
Study Objectives 
To determine the efficacy and safety of:  
a) seven ascending oral moxidectin dosages in adults 
infected with S. stercoralis, namely placebo, 2 mg, 4 mg, 
6 mg, 8 mg, 10 mg, 12 mg and to measure moxidectin 
disposition in adults using a microsampling device.  
b) the recommended dose moxidectin (i.e. the most 
promising dosage identified in trial A; 8 mg) in comparison 
to the standard treatment dose of ivermectin (200 µg/kg) 
in adults infected with S. stercoralis. 
 
Our 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:  
a) in a dose finding study  
placebo, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 
mg moxidectin  
b) in a parallel group trial 


StrongMoxi, Protocol, v2.2, 01.07.2020 
 
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8 mg moxidectin (absolute value depends on 
results of (A)), and 200 µg/kg ivermectin. 
 
The secondary objectives of the trial are: 
1) to evaluate the safety and tolerability of the dose-
dependent treatment regimes. 
2) to evaluate the safety and tolerability of moxidectin 
compared to ivermectin.  
3) to compare the larvae reduction rate (LRR) of the 
different treatment regimens against S. stercoralis 
(trial A and B). 
4) trial A: to determine an exposure- (including Cmax, 
AUC and tmax) -response correlation of moxidectin in 
adults. 
5) trial A: to compare the exposure-response of moxidectin 
using venous and capillary blood.    
6) to evaluate the cure rate of the different moxidectin 
treatment regimens against co-infection.  
7) trial A: to determine the population PK parameters of the 
optimal dose of moxidectin in the treatment of S. 
stercoralis. 
8) trial 
B: 
to 
relate 
socioeconomic 
characteristics 
(possession of indicator assets), access to sanitation, 
water facilities, and hygiene and environmental reservoirs 
behaviour to infection intensity 
Study design 
Single blinded, randomized controlled trial (trial A) (participants 
and lab technicians are blinded); double blinded randomized 
controlled non-inferiority trial (trial B) 
Study product / 
intervention 
Administration of a single oral dose of moxidectin or ivermectin 
Comparator(s) 
Matching placebo (trial A, B), Ivermectin (trial B) 
Key inclusion / 
Exclusion criteria 
Inclusion: Adults (≥ 18, <65 years) infected with S. stercoralis, 
absence of major systemic illnesses, written informed consent 
signed by individual 
 
Exclusion: Any abnormal medical conditions or chronic disease, 
negative diagnostic result for S. stercoralis, no written informed 
consent by individual. Pregnant women, lactating women or 
women planning to become pregnant within the next six months 
Primary Endpoints 
CR on S. stercoralis 
Secondary Endpoints 
LRR against S. stercoralis, safety and pharmacokinetic 
parameters in S. stercoralis  infected populations 


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Exploratory Endpoints 
Co-infection 
Interim Analyses 
None 
Study Duration 
8 weeks (trial A) / 8 weeks (trial B)  
Schedule 
08/2019 of first-participant in (planned) 
08/2021 of last-participant out (planned) 
Measurements & 
procedures 
Three stool samples will be collected at baseline if possible on 
three consecutive days or otherwise within a total maximum of 6 
days and analysed by a quantitative Baermann method (in 
duplicates) for S. stercoralis infection. Co-infection with T. 
trichiura, A. lumbricoides and hookworm infection will be identified 
using duplicate Kato-Katz thick smears on stool samples from two 
consecutive days. 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 treatment day.  
The adults will also be interviewed before treatment, 3 and 24 
hours as well as 28 days after treatment about the occurrence of 
AEs. The efficacy of the treatment will be determined 21-28 days 
post-treatment by collecting another three stool samples. All stool 
samples will be examined with duplicate Baermann assays and 
Kato-Katz thick smears and recorded quantitatively.  
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 28 days 
post treatment to evaluate pharmacokinetic parameters (trial A). 
For validation of the analytical method the subsample of one study 
arm (8 mg, trial A) will undergo venous blood sampling in addition 
to finger pricking. 
To all participating households, a brief questionnaire will be 
administered 
assessing 
information 
on 
socioeconomic 
characteristics (possession of indicator assets) and access to 
sanitation, water facilities, and hygiene behaviour at first visit. 
Additionally, soil and water samples at different sites will be taken. 
Statistical Analyses 
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) 


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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.  
Trial A: 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.  
Noncompartmental 
and 
nonlinear 
mixed-effects 
(NLME) 
modeling will be used to determine pharmacokinetic parameters.  
Trial B: The non-inferiority margin is set to 10%-points, i.e. If the 
lower bound of the 95% CI of the differences in cure rates is 
greater than -0.1 we conclude that moxidectin is non-inferior to 
ivermectin. 
GCP statement 
This study will be conducted in compliance with the protocol, the 
current version of the Declaration of Helsinki, ICH-GCP E6 (R2) 
as well as all national legal and regulatory requirements. 
Key explanation for the 
inclusion of adults 
This study will be carried out in adults, since an infection with S. 
stercoralis occurs most often in adults and the efficacy of different 
dosages of moxidectin and the non-inferiority to ivermectin in 
adults was not yet determined.  
Recruitment procedure 
(A) A dose-finding (DF) study on efficacy, safety and - for a 
subgroup of a total of 90 participants on PK parameters - 
on moxidectin will be conducted in 210 infected adults 
from rural communities situated in Nam Bak province in 
northern Laos (trial A: DF trial).  
 
(B) The parallel group study between moxidectin and 
ivermectin will be conducted as a non-inferiority trial with 
a margin of 10% in Laos and Cambodia recruiting 350 
infected adult rural community members. 
 
The studies will be conducted in areas with moderate to high 
infection risk in Nam Bak province in northern Laos (prevalence: 
> %) of S. stercoralis identified from earlier studies and/or based 
on experience of the local collaborating teams. 
Coverage of damages 
 Policy No: 021805872, Lao Viet  
Storage of data and 
samples 
for 
future 
research aims 
After the study has been completed all samples will be destroyed 
and case report forms will be kept for a minimum of 15 years 
(chapter 10). 


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Conflict of interest in 
relation 
to 
the 
investigated drugs 
We declare no conflict of interest in relation to the investigated 
drugs. 
 
 


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V. 
Abbreviations 
 
AE 
Adverse event 
AUC 
Area under the curve 
CI 
Confidence interval 
CR 
Cure rate 
CRF 
Case report form 
DALYs 
Disability-adjusted life years 
DBS 
Dried blood spot 
DF  
Dose finding  
DSMB 
Data and safety monitoring board 
EKNZ 
Ethikkommission Nordwest- und Zentralschweiz 
GCP 
Good clinical practice 
Hb 
Hemoglobin 
ICH 
International council for harmonization of technical requirements for 
pharmaceuticals for human use 
IEC 
Independent ethics committee 
LC-MS/MS 
Liquid chromatography tandem mass spectrometry 
LPG 
Larvae per gram 
LRR 
Larvae reduction rate 
NLME 
Nonlinear mixed-effects 
NTD 
Neglected tropical disease  
PI 
Principal investigator 
PK 
Pharmacokinetics  
SAE 
Serious adverse event 
WHO 
World Health Organization 


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2. Background information 
Over the last decade, increasing evidence has linked major neglected tropical diseases (NTDs) 
to significant adverse impacts on human and economic development. NTDs affect more than 
one billion people globally, in particular poor, and marginalized tropical populations, and 
contribute to an estimated 3.3 million disability-adjusted life years (DALY) lost globally. NTD 
also includes soil-transmitted helminthiasis such as strongyloidiasis covered in this clinical 
study [1].  
 
Strongyloides stercoralis is a soil-transmitted nematode found almost worldwide, though with 
largest prevalence in tropical and subtropical regions, as an example Lao PDR [2-4], and 
belongs to the most neglected infections among the NTDs.  
Infectious larvae are found in humid soil that is contaminated with feces. Upon penetration of 
the intact skin of their host, S. stercoralis can reproduce within their human host. This 
endogenous autoinfection may result in long-lasting infections, which is not seen in other soil-
transmitted helminth infections. Furthermore, S. stercoralis is known for its unique and 
threatening feature to cause systemic infection. Not surprisingly, without appropriate therapy, 
thus infections do not resolve and may persist for life. In case of immunodeficiency the 
infections are severe if not even life-threatening. However, most infections, chronic low-
intensity infections, in particular, remain non-specific and might be expressed as suffering from 
malnutrition, physical and cognitive retardation, and reduced work performance [5]. S. 
stercoralis infections are typically most intense and debilitating in adults causing significant 
morbidity [6-8].  
 
Today, chemotherapy combined with health education programs, remain the core to reduce 
the serious health impacts. The currently advocated treatments by the World Health 
Organization (WHO) are a single dose of ivermectin or multiple doses of albendazole, which 
has a lower efficacy compared to ivermectin [9, 10]. Since drug resistance is a threat and the 
drug pressure is high it is of uttermost importance to develop new treatment alternatives. 
Among new candidates in the human anthelminthic drug development pipeline, moxidectin, a 
macrocyclic lactone might be an excellent alternative. Moxidectin has been approved recently 
by the Food and Drug Administration (FDA) for 
use against onchocerciasis. 
(http://www.who.int/tdr/news/2018/moxidectin-approved-as-treatment-for-river-blindness/en/) 
[11]. The drug offers some advantages over ivermectin. First of all, moxidectin is used weight 
independent (for onchocerciasis at an 8 mg fixed dose), which renders the administration 
easier to handle, especially when treating large communities. Second, moxidectin has been 
shown to have a lower neurotoxic potential than ivermectin [12]. Thirdly, the pharmacokinetic 


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profile of moxidectin in healthy individuals (very long t1/2, and a large Vd/F, compared to 
ivermectin) arises prospects for efficacy also against long-term parasitic activity – as is 
particularly important when treatment of S. stercoralis is desired [13]. Finally, most importantly 
moxidectin has been used successfully in veterinary medicine against ivermectin-resistant 
strains [14].  
 
The clinical significant adverse advents of moxidectin are though very similar to those of 
ivermectin and a consequence of excessive concentration. The drug is typically used as a 
single oral dose (8 mg) in patients aged 12 years and older and evaluated as an extremely 
safe drug. Most common side effects include hypotension, itching, headache, abdominal pain, 
fever, dizziness or diarrhea. Serious or even fatal encephalopathy may occur in patients co-
infected with Loa Loa. Furthermore, moxidectin is known to worsen onchodermatitis in patients 
with hyperactive onchodermatitits. Laos and Cambodia are not endemic neither for Loa Loa 
nor onchodermatitits and thus these symptomatic advents shall not constitute a risk in our 
study. Nevertheless patients with symptoms for onchodermatitits (severe itching, bumps under 
the skin, blindness) will be excluded from the study. Additionally, although conclusive 
teratogenic data on moxidectin are missing, decreased fetal survival and increased fetal born 
with malfunctions is observed in some animals studies. Thus we do not see it recommended 
using moxidectin with pregnant female and pregnant patients will strictly be excluded. Last, 
owing to the lipophilic nature of moxidectin, extraction of moxidectin to the breast milk of 
nursing mothers is very likely and could be demonstrated in lactating cows. The risk of 
moxidectin in nursing infants is though unknown. Breastfeeding females will be excluded in 
this study.  
 
In a small exploratory study using the veterinary formulation, a single dose of 8 mg of 
moxidectin, and a small sample size (127 participants) moxidectin has been found to be 
efficacious against S. stercoralis (cure rates of 93.7%) and its tolerability confirmed also in 
patients [15].  
 
Yet, despite the attractive attributes of moxidectin and its promising potential in the treatment 
of S. stercoralis it remains off-label. First of all, the efficacy of the human formulation against 
S. stercoralis infections has not been assessed to date, neither has the optimal dosage been 
elucidated. A single dose of 36 mg moxidectin in healthy adults was the highest single dose 
tested to date that still represented a well-tolerated dose [13]. The 12 mg, therefore, selected 
as the highest dose in our study to elaborate a dose-response relationship for the use of 
moxidectin in S. stercoralis infections will not pose any health risk. 
 


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Second, to date pharmacokinetic studies of moxidectin have been conducted exclusively in a 
low number of healthy adults and consequently the pharmacodynamic behavior of moxidectin 
is completely unknown. [13, 16]. Yet, a PK characterization is central to understand the human 
body’s response to a drug, especially in populations that physiologically differ from healthy 
adults. Physiological abnormalities like mal- or undernutrition and intestinal worms, such as S. 
stercoralis, can potentially affect the PK of a drug [17, 18]. Being minimal invasive, minimal 
painful, simple and rapidly performed, micro-blood sampling (e.g. the dried blood spot (DBS)) 
has developed into the method of choice for PK studies and will be also used in this study. 
Micro-blood sampling has been repeatedly proven to correlate well with the standard method 
that uses venous blood [19-22]. Micro blood sampling analysis has not been used to measure 
moxidectin blood levels and, therefore, requires a validation. For this purpose, a formal 
validation, using blood samples from two vascular sides, will be performed in parallel; 
supporting and confirming the linearity between venous and capillary blood also for moxidectin. 
 
Last, it would be crucial to elucidate if moxidectin at an appropriate dose could serve as an 
alternative to ivermectin, which is to date one of the very few but the drug of choice against S. 
stercoralis.  
 
In view of remaining knowledge gaps of the optimal doses of moxidectin against S. stercoralis 
as well as insufficient evidence on safety and efficacy parameters our study aims in a first step 
to thoroughly investigate the efficacy and safety of ascending doses of moxidectin (2 mg, 4 
mg, 6 mg, 8 mg, 10 mg, 12 mg versus placebo) against S. stercoralis infection, complemented 
by PK studies. Once the optimal dose of moxidectin has been identified in this phase 2a trial 
(trial A: DF study), we aim in a second study to compare the safety and efficacy of the single 
best dose of moxidectin to the standard dose of ivermectin in two phase 2b trial settings (trial 
B: parallel group study). This study will be complemented by assessing socioeconomic factors, 
household characteristics and behaviors, using a household questionnaire. Moreover, we will 
inform about potential environmental risk factors. 
 
 
 
 


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3. Trial objective and purpose 
The primary study objectives are  
(A) To determine the nature of the dose-response (efficacy in terms of cure rate) using oral 
moxidectin dosages: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg and placebo in a total of 
210 adults infected with S. stercoralis (trial A: DF study).  
(B) To determine if the efficacy in terms of cure rate of an oral single optimal dose of 
moxidectin (8 mg based on the outcome of (A)) is non-inferior to the standard dose of 
a single oral ivermectin application (200 µg/kg), in 350 infected adults in two settings. 
The non-inferiority margin is set to 10%-points (trial B: parallel group study).  
 
The secondary study objectives are 
1.) To compare the efficacy based on larvae reduction rates of ascending oral moxidectin 
dosages in a total of 210 adults infected with S. stercoralis. 
2.) To determine safety & tolerability of ascending oral moxidectin dosages in a total of 210 
adults infected with S. stercoralis. 
3.) To comparatively assess the efficacy based on larvae reduction rates moxidectin versus 
ivermectin (200 µg/kg), the current drug of choice, against S. stercoralis in 350 adults 
infected with S. stercoralis. 
4.) To determine safety & tolerability of moxidectin versus ivermectin (200 µg/kg), the current 
drug of choice, against S. stercoralis in 350 adults in two countries infected with S. 
stercoralis. 
5.) To determine pharmacokinetic parameters in 10 adults infected with S. stercoralis, after 
oral moxidectin administration of 8 mg, using venous as well as capillary blood allowing 
the validation of the micro sampling analysis to measure moxidectin blood levels. 
6.) To measure moxidectin deposition and determine exposure (including Cmax, AUC and tmax)-
response correlation using a microsampling technology after oral moxidectin administration 
of 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg versus placebo in a total of 90 adults infected 
with S. stercoralis. 
7.) To determine the population PK parameters of the optimal dose of moxidectin in the 
treatment of S. stercoralis. 
 
 


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4. Methodology 
4.1. Primary and secondary endpoint 
CR (i.e. conversion from being larvae positive pre-treatment to larvae negative post-treatment) 
is the primary endpoint. In addition, LRR and key PK parameters will be determined and safety 
& tolerability of treatment evaluated (secondary end points). CRs against co-infections are 
considered as exploratory endpoints. 
4.2. Type of trial 
Single blinded, randomized placebo-controlled, dose-ranging trial (trial A: DF study) 
(participants and lab technicians are blinded). 
Double blinded, randomized, non-inferiority trial (trial B: parallel group study). 
The PK sub-studies of trial A and trial B are single blinded.  
4.3. Trial design 
Two randomized-controlled trials will be conducted; a dose-ranging study (trial A) and a parallel 
group study (trial B), with seven and three treatment arms, respectively to be followed-up each 
over a 21-28 days period. The second comparative trial will be conducted as a non-inferior 
study with a non-inferiority margin of 10%-points. 
(A) The DF study (Figure 1, top) is designed as a seven-armed trial including arms with 
ascending dose administration of moxidectin: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 
mg and a placebo-arm.   
(B) The parallel group study (Figure 1, bottom) is designed as a two-armed trial 
including one arm with a single drug administration of a standard dose of ivermectin 
(200 µg/kg) and one arm with a treatment of a single best dose of moxidectin (8 
mg, according to the findings in (A)). The optimal dose of findings in (A) are 
evaluated as the dose that is high enough to demonstrate efficacy in the target 
population, yet low enough to minimize safety concerns and adverse events.  
 
 
 


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The two study cohorts are presented in the figures below:  
 
 
Figure 1. Design and timeline of the DF trial (top) and the parallel group trial (bottom) to be implemented. All sample sizes assume 
a drop-out of 10 %.  
 
 
4.3.1. Baseline larval count 
At baseline, all participants will be asked to provide three stool samples (if possible on three 
consecutive days or otherwise within a total maximum of 6 days) [23, 24]. The stool samples 


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will be collected until a total of 210 and 350 S. stercoralis-infected adults are registered (two 
out of three stool samples show more than 0.4 LPG (trial A) or 0.1 LPG (trial B), in 10 g of stool 
sampled per person and time point) in the two studies, respectively. As diagnosing very low-
intensity chronic infections remains a major challenge for quantitative and qualitative analysis 
for S. stercoralis only low/moderate to high infection patients are included in trial A (LPG >0.4 
on two out of three samples). This inclusion criterion has been shown to result in a diagnostic 
sensitivity of more than 97% to close to 100%. [24]. 
Firstly, a quantitative Baermann funnel concentration technique will be used for the quantitative 
assessment of Strongyloides stercoralis infections [24-26] using stool samples from three 
different (optimal consecutive) days. 5 g stool sample (the stool container with the sample will 
be weighted before and after the Baermann test was set up) will be placed on gauze inserted 
into a glass funnel and covered with preheated water to 36°C. Following two hours of artificial 
light exposure, the collected liquid will be centrifuged and the sediment prepared for analysis 
by microscope. Duplicate Baermann will be prepared from each stool sample [27, 28]. 
Secondly, from two stool samples from each participant a duplicate Kato-Katz thick smear will 
be prepared to detect co-infection with any of the three major soil-transmitted helminthic 
infections (STHs), namely Ascaris lumbricoides, Trichuris trichiura and the hookworms 
(Necator americanus and Ancylostoma duodenale) [29]. If additional coinfections are 
observed, they will be assessed likewise. 
The slides from the Baermann and Kato-Katz thick smears will be analyzed under a 
microscope by experienced technicians and a subsequent independent quality control of 
sample results (approximately 10%) will be conducted. S. stercoralis larvae will be counted 
quantitatively and eggs recorded for the different helminths species separately and 
qualitatively assigned as egg positive or negative. Results are considered correct if the 
following tolerance margin is not exceeded: (i) No difference in presence/absence S. 
stercoralis, (ii) egg/larvae counts are +/-10 eggs/larvae for counts ≤100 eggs/larvae or +/-20% 
for counts >100 eggs/larvae (for each species separately) [30]. In case discrepancies above 
the tolerance margin are noted in one or more slides, all slides are re-read by the local 
technicians. The new results are discussed, so that in case of discordant results, slides can be 
re-evaluated to reach consensus. Infection intensity expressed as the arithmetic and geometric 
mean egg/larvae count per gram of stool will be calculated for each treatment arm. All 
microscopically analyzed Baermann samples as well as the Kato-Katz thick smears will be 
destroyed within one day (after passing the quality control). 
 
 


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4.3.2. Physical and clinical examination 
At baseline, the medical history of S. stercoralis-infected participants in the study will be 
assessed with a clinical and physical examination carried out by the study clinician, who will 
assess weight, height, body temperature, pulse rate, blood pressure. Hemoglobin (Hb) levels 
will be detected using HemoCue to exclude severely anemic participants (below 80 g/l in adults 
according WHO) [31]. To avoid accidental treatment of pregnant women all female participants 
will be asked to provide a urine sample of at least 10 ml to be subjected to a pregnancy RDT. 
Women will be individually counselled that they should not become pregnant during the entire 
study period and will be interviewed if they are currently breastfeeding or planning to become 
pregnant. Any symptoms and abnormalities prior to treatment will be recorded on the case 
report form (CRF). 
4.3.3. Adverse effects assessment 
All participants will be kept for observation for at least 3 hours following each morning treatment 
for any acute adverse events and additionally will be interviewed and examined about existing 
and emerging clinical symptoms (i.e. headache, abdominal pain, itching, nausea, vomiting, 
diarrhea, body temperature, and allergic reaction) before treatment (baseline examination), 3 
hours, 24 hours and 28 days after treatment (adverse effects assessment) to determine the 
occurrence of AE (see chapter 6.2). Any symptoms will be recorded in the CRF and immediate 
action will be perused (see chapter 6). 
4.3.4. Assessment of efficacy after treatment 
The efficacy of the treatment will be determined 28 days post-treatment by collecting another 
three stool samples, which will be microscopically examined for S. stercoralis applying each 
duplicate Baermann technique as well as for potential co-infection with A. lumbricoides, T. 
trichiura and hookworm eggs using each duplicate Kato-Katz thick smears on two stool 
samples.  
Participants will be considered S. stercoralis cured if no larvae have been found in any of the 
stool samples. Infection was calculated as larvae per gram stool. LPG will be assessed by 
calculating the mean of the larvae counts from the three duplicate Baermann assays and 
adjusted to the previously weighted used amount of stool sample. At the end of the study (day 
21) all participants remaining positive for S. stercoralis will be treated with ivermectin (200 
µg/kg), the current standard drug against S. stercoralis [9]. 
 
 
4.3.5. Pharmacokinetic studies 
Exposure-response correlation studies will be performed in a maximum of 15 participants per 
treatment arm (90 patients in total) (trial A: DF study). Since moxidectin is known to be better 


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absorbed in humans after a high-fat meal was consumed participants will receive a local high-
fat breakfast prior to treatment [16]. Upon oral intake moxidectin levels in blood will be 
quantified with time using a micro sampling device. Therefore, capillary blood will be taken 0, 
2, 4, 8, 24, and 72 hours, 7 and 28 days post-dosing (trial A). Micro sampling presents as one 
of the simplest, safest and least invasive study protocols. In our lab different blood micro-
sampling techniques, including dried blood spots (DBS) and Mitra®, are currently under 
investigation to quantify moxidectin extracted in human blood samples. Following method 
development according to the U.S. FDA guidelines, the best protocol will be selected for the 
pharmacokinetic studies (i.e. DBS or Mitra®). 
 
As yet the micro-blood sampling analysis has not been used to measure moxidectin blood 
levels in S. stercoralis, a formal validation will be performed next to the measurement of the 
PK values. For this purpose an additional blood sample will be taken from the venous side to 
demonstrate that the capillary and venous blood correlate satisfactory or to calculate the 
conversion coefficient. Venous blood will be withdrawn by cannulation from the same 10 adults 
of one treatment arm (8 mg) at identical time points post-dosing (trial A) [13, 16, 32]. 
In more detail, capillary blood (± 0.1 ml) will be collected by middle or ring finger tip puncture 
using a finger pricker (e.g. Accu-chek Softclix Pro®, Roche). Sampling will be conducted at the 
specified time points in doublets. A few drops of blood will be transferred at each time point on 
filter paper (Whatman) or on Mitra® sticks and dried for approximately 1 hour. The dried blood 
spot cards or Mitra® will be transported to Basel and stored properly until analysis. Moxidectin 
will be quantified using the 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 1-5 ng/ml. Quality control samples 
will be included in the study and its measured concentrations used to determine between-run 
and overall precision and accuracy of the analysis. 
 
Venous blood (± 4 mL) will be collected in EDTA covered Vacutainer® tubes through an i.v. 
catheter placed in an antecubital arm vein. The indwelling catheter will be inserted in the arm 
not earlier than 1 hour before the beginning of the blood sampling. For the purpose of keeping 
the catheter patent, 0.9% sodium chloride (NaCl) will be slowly infused i.v. (1 drop per 2-3 
seconds). Dilution artifacts will be avoided by interrupting the i.v. 0.9% NaCl drip prior to 
collection of the blood sample. In addition, approximately 0.5 ml of blood will be drawn through 
the catheter and wasted. Directly after the collection of the required blood volume (4 ml), the 
Vacutainer® tubes will be slowly tilted backwards and forwards (no shaking) to solve the anti-
coagulant. 1 ml of blood will be transferred in a labeled tube, within 30 minutes post sampling. 
The remaining blood in the Vacutainer® will be centrifuged at about 3000 rpm for 10 min and 


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4°C to obtain plasma, which will be pipetted in another labeled polypropylene tube. The plasma 
and blood tubes will be kept in an upright position at -20 °C until analysis. The concrete time 
points of withdrawal of each blood sample will be entered in the form. 
 
 
4.3.6. Questionnaire 
A household-based questionnaire will be administered to one member of each participating 
household to adjust for known influencing factors with regard to reinfection and infection 
intensity [33, 34] in the subsequent analysis and to identify risk factors for residual infections 
[35]. The questionnaire will include assessment of / questions about information on 
socioeconomic characteristics (e.g structure, condition and amenities), access to sanitation 
and water facilities (e.g. latrine, toilet, shower, water source) as well as hygiene behavior (e.g. 
defecation, hand washing, water use). The questionnaire is based on the core questions 
recommended by WHO and UNICEF. To assess environmental risk factors, soil and water 
samples will be taken at specific sites in the village and analyzed microscopically. 
 
4.4. Measure to minimize bias 
Study participants eligible for treatment will be randomly assigned to one of the seven 
treatment arms (trial A: DF study) or to one of the two treatment arms (trial B: parallel group 
study) using a computer-generated stratified by 3 levels of baseline infection intensity (light 
≥0.4 (trial A) or 0.1 (trial B) – 1 LPG, moderate >1-10 LPG and heavy >10 LPG), block 
randomization code. The random allocation sequence with varying random blocks of 7 or 14 
(trial A) and 2 or 4 (trial B) will be provided by a statistician not involved in enrolment, treatment, 
and data collection. Stratification will guarantee similar proportion of participants with different 
infection intensities in all treatment arms. The number of light vs moderate vs. heavy infections, 
however, are not expected to be equal in each arm, depending on the distribution of infection 
intensity in the recruited cohort. The codes will be held in a locked cabinet at the Swiss Tropical 
and Public Health Institute. A copy of this code will be kept in a sealed envelope by one of the 
co-investigators (will only be opened in emergency situations, determined by the principal 
investigator upon consultation with the co-investigators). The blinding will be maintained 
throughout the trial until data entry and processing are complete and the data have been 
verified. Following release of the final data, the randomization codes will be released. 
In previous studies [36] we have observed moderate cure and larvae reduction rates in placebo 
treated children which are in most cases likely due to the imperfect sensitivity of anthelminthic 
diagnostics. Participants treated with placebo will be treated at follow up (4 post treatment) 
with ivermectin (200 µg/kg). This treatment delay does not cause noteworthy harm. 


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4.5. Study duration and duration of subject participation 
The trial will last a maximum of 2 months, each (trial A and B). The screening for the baseline 
will start four weeks prior to the treatment. Follow up screening will take place 3-4 weeks post-
treatment. Schedules of visits are summarized below (Table 1). 
 
 
4.6. Schedule of visits 
Table 1. Schedule of visits of DF (trial A) and parallel group (trial B) study.  
 
Screening /  
 
Follow up 
Time point 
Day 
-28 
Day 
-1-3 
0 h 
Randomization and administration of  treatment 
3 h 
24 h 
Day 28 
Informed consent 
X 
 
 
 
 
 
Diagnosis (stool 
examination) (a) 
X 
 
 
 
 
X 
Questionnaire 
X 
 
 
 
 
 
Medical history (c) 
 
X 
 
 
 
 
Clinical examination (d) 
 
X 
 
 
 
 
Physical examination (e) 
 
X 
 
 
 
 
Randomization 
administration of treatment 
 
 
X 
 
 
 
Capturing AEs (f) 
 
 
 
X 
X 
X 
Capturing SAE (f) 
 
 
 
X 
X 
X 
(a) on three stool samples duplicate Baermann assays and on two stool samples duplicate Kato-Katz thick smears.  
(b) date of birth, age, sex, height, weight, body temperature, pulse rate, blood pressure, hb measurement, pregnancy test and 
recording of breastfeeding 
(c) information gained by asking specific questions concerning chronic disease and concomitant medication. 
(d) investigation for signs of disease: head ache, abdominal pain, nausea, vomiting, diarrhea, itching, other symptoms.  
(e) examination on ear, nose, throat, eyes, lungs, lymph nodes and skin. 
(f) a standardized symptom questionnaire is used, that includes the recording of headache, abdominal pain, itching, nausea, 
vomiting, diarrhea, allergic reaction, others 
(g) only in trial B 
 
 
5. Selection of the trial subjects 
5.1. Recruitment 
The studies will be carried out in adults in areas endemic for S. stercoralis in Laos and 
Cambodia.  


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The adult community members will be invited to participate in an information meeting to explain 
the purpose and procedures of the study, including potential benefits and risks. Potential 
participants will be encouraged to ask questions in an open discussion forum.  
Those adults who are interested in the study will be invited to complete the process of informed 
consent. See section 9.3 for details on obtaining informed consent. Only those participants 
who have written informed consent will be assessed for study eligibility criteria during screening 
procedures. 
 
5.2. Inclusion criteria 
1.  
Males and females of age 18 – 65 infected with S. stercoralis (positive by at least two 
Baermann assays of two different days and infection intensities of at least 0.1 LPG in 
the two stool samples (5g stool / Baermann assay). 
2. 
Written informed consent signed by the participant him/herself. In case the person is 
illiterate, an impartial witness that can read and write has to sign the consent and the 
illiterate participant to give a thumb print. 
3. 
Agree to comply with the study procedures, including to be examined by a study 
physician at the beginning of the study and to provide three stool samples at the 
beginning (baseline) and three stool samples approximately four weeks after treatment 
(follow-up).  
 
Exclusion criteria 
1. 
Presence of acute or uncontrolled systemic illnesses (e.g. severe anemia) as assessed 
by a medical doctor, upon initial clinical assessment. 
2. 
History of severe chronic disease or major systemic illnesses, e.g. severe anemia, 
severe chronic heart, liver or renal disease as asked by the medical doctor, upon initial clinical 
assessment. 
3. 
Prior treatment with anthelmintics (eg, diethylcarbamazine [DEC], suramin, ivermectin, 
mebendazole or albendazole) within 4 weeks before planned test article administration.  
4. 
Attending other clinical trials during the study. 
5. 
Positive pregnancy test, lactating women and/or women planning to become pregnant 
within the next 6 months. 
 
Participants who were diagnosed with a STH infection, but who were excluded from the study 
due to one or several of the above-mentioned exclusion criteria, including withdrawals will be 
offered standard anthelminthic treatment. Participants suffering from clinical malaria (fever plus 
positive diagnostic test) will be treated according to national guidelines. 


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5.3. Criteria for discontinuation of trial 
A subject can be discontinued from the study for the following reasons: 
1. 
withdraws from the study (this can happen anytime as participation is voluntary 
and there are no further obligations once an adults withdraws). 
2. 
at the discretion of the principal investigator, if the participant is not compliant to 
the requirements of the protocol. 
Discontinued subjects will not be replaced. If, for any reason, a subject is discontinued from 
the study before the end of treatment evaluations, the safety procedures planned (AEs 
monitoring) will be conducted. Data obtained prior to subject’s withdrawal will be included in 
analysis. Data of withdrawn patients are fully anonymised once analysis is completed.  
5.4. Treatment of subjects 
2 mg tablets of moxidectin will be obtained from Medicines Development for Global Health 
(MDGH), Australia. Ivermectin (3 mg) will be purchased from Merck, Switzerland. Matching 
placebo tablets (moxidectin and ivermectin) will be obtained from the Medicines Development 
for Global Health (moxidectin) and produced and a certificate of manufacture and analysis 
provided by the University of Basel (ivermectin). The appropriate doses will be calculated and 
the correct amount of moxidectin and placebo (trial A) and moxidectin, moxidecin placebo or 
ivermectin or ivermectin placebo tablets (trial B) will be administered to all participants. Due to 
blinding the tablets will be repacked into neutral separate opaque plastic bags each containing 
the adequate dose of moxidectin tablets and/or placebo tablets (trial A). In trial B, the tablets 
will be handed out from the drug container according to the randomization list. Each person 
will receive (i) either 4 moxidectin or 4 moxidecin placebo tablets and (ii) the number of 
ivermectin tablets with regard to their weight category or the corresponding number of 
ivermectin placebo tablets. The tablets will as long as applicable be stored in the original 
package and at any time (except treatment day) be stored according to manufacture 
prescription, sealed and away from light.  
The principal investigator(s) or co-investigator(s) is responsible for drug accountability at the 
study site. Maintaining drug accountability includes careful and systematic study drug storage, 
handling, dispensing and documentation of administration. 
 
Treatment and blood sampling (capillary blood sampling for a total of 90 participants, in trial A 
and venous blood sampling for 10 patients (trial A)) will be done community-based in local 
temples, that are quiet and spacious locations, where people like to gather and organize 
meetings. Infrastructure as required for the study needs (i.e tables, chairs, a fridge, a cover 
from rain and sun) will be installed as necessary at the specific study days. Opportunities 


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(approximately three daybeds) will be provided to comfortably withdraw the venous blood (4 
samples on day 1 and 4 samples within the next 28 days) and to provide a possibility to lie 
down in case of an arising unwell feeling. Participants will receive a breakfast two hours prior 
to treatment as well as lunch during the day once absorption of the drug is complete.  
 
On each treatment day a subgroup of participants will be treated with the different dosages. 
All drugs will be administered in the presence of the investigator(s) or co-investigator(s) and 
the physician, and ingestion confirmed. This will be recorded with the time and date of closing. 
Subjects will be asked not to take any drugs other than those prescribed by the study medical 
team. After ingestion of the medication, the subjects will be observed for 3 hours to ensure 
retention of the drug. Vomiting within 1-hour post-dosing will require re-dosing. The subjects 
will not be allowed more than one repeated dose. No re-administration will be needed for 
subjects vomiting after one hour. In case any SAE will be observed, the study will be put on 
hold until the data has been reviewed and a decision taken within the entire study team whether 
the study can be continued or has to be stopped. On the treatment day, participants presenting 
a serious medical situation as judged by the physician of the project will be kept at the hospital 
level under close supervision by the medical team. Also, in order not to break the surveillance 
of the undesirable effects of those whom we will allow to go back home at the end of the 
treatment day, security measures will be taken: (i) a card containing at least three phone 
numbers of the investigators and the study physician will be given to the participant himself.  
We will be working with adults in rural areas. Participants who are involved in agricultural 
activities and migrating between locations will be provided with phone numbers so to follow 
them up with the help of health workers in case AEs occur. 
5.5. Concomitant therapy 
All medications taken one month before and during the study period must until the last stool 
examination at day 28 (trial A) post treatment (follow-up) be recorded with indication, dose 
regimen, date and time of administration. 
 
Medication(s)/treatment(s) permitted during the trial 
- Analgesics and antipyretics are allowed to be given to the subjects in case of fever, 
antiemetics to prevent nausea and vomiting and/or antibiotics to prevent or treat 
bacterial superinfection. 
Medication(s)/treatment(s) NOT permitted during the trial  
- No other active drugs against helminths are permitted during the trial 
 


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6. Assessment of safety 
6.1. Adverse event definition 
Few adverse events have been reported following moxidectin or ivermectin administration in 
STH-infected individuals. The most common AEs were abdominal cramps, headache, nausea, 
diarrhea, fever and vertigo [11, 12, 36, 37]. 
 
The observation time for AE starts when the treatment is initiated. 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 examination and findings will be 
recorded. An emergency kit will be available on site to treat any medical conditions that warrant 
urgent medical intervention. Participants will also be interviewed 3, 24 hours, 28 days after 
treatment about the occurrence of AEs. 
Information on all AE (incidence, onset, cessation, duration, intensity, frequency, seriousness 
and causality) will be entered immediately in the source document, and also in the appropriate 
AE module of the case report form. For all AEs, sufficient information will be pursued and/or 
obtained so as to permit i) an adequate determination of the outcome of the event (i.e. whether 
the event should be classified as a SAE); and; ii) an assessment of the casual relationship 
between the AE and the study treatments. Intensity of AE will be judged by the study physician, 
following guidelines by the European Medicine Agency (Note for Guidance on Clinical Safety 
Data Management). 
 
 
6.1.1. Types of adverse events 
The term “adverse event” is defined as:  
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship 
with this treatment.  
 
An AE can therefore be:  
a) Any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
b) Any abnormality detected during physical examination.  
 


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The medical conditions present at the initial trial visit that do not worsen in severity or frequency 
during the trial will not be defined as AEs but as well be considered baseline medical 
conditions. 
These data will be recorded on the appropriate CRFs, regardless of whether they are thought 
to be associated with the study or the drug under investigation. “Associated with the use of the 
drug” means that there is a reasonable possibility that the event may have been caused by the 
drug. 
 
 
6.1.2. Severity grading 
Adverse signs or symptoms will be graded by the investigator as mild, moderate, severe or life 
threatening 
according 
to 
the 
following 
definitions 
(https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf). 
 
 
Grade  
 
Definition 
 
 
 
 
 
 
 
1: 
 
 
mild adverse events 
 
2: 
 
 
moderate adverse events. 
 
3: 
 
 
severe adverse events. 
 
4: 
 
 
life threatening or disabling adverse events. 
 
5:  
 
 
death related to adverse events. 
 
The observation time for adverse events starts when the treatment is initiated and continues 
until 28 days post-treatment. For the purpose of this trial, disease progression and relapse will 
be considered as treatment failure, not as an AE. 
 
6.1.3. Relatedness 
Relatedness will be assessed as defined below based on the temporal relationship between 
the AE and the treatment, known side effects of treatment, medical history, concomitant 
medication, course of the underlying disease and trial procedures. 
 
Possibly related: an AE which can medically (pharmacologically/clinically) be attributed to the 
study treatment. 
Unrelated: an adverse even which is not reasonably related to the study treatment. A 
reasonable alternative explanation must be available. 
 
An AE that is determined to be related to the administration of a study product is referred to as 
an “adverse drug reaction.” 


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6.1.4. Types of adverse events 
Expected adverse event: Risks or events reported in the literature for moxidectin and/or 
ivermectin. 
Unexpected adverse event: An unexpected event is any AE that is not identified in nature, 
severity, or frequency in the scientific literature. 
 
 
6.1.5. Serious adverse events 
According to the ICH “Clinical Safety Data Management: Definitions and standards for 
expedited Reporting E2A” 
(https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2A/Step
4/E2A_Guideline.pdf) a serious SAE includes any event (experience) or reaction in any 
untoward medical occurrence that at any dose: 
1. 
is fatal, results in death; 
2. 
is life threatening, meaning, the subject was, in the view of the investigator, at 
immediate risk of death from the reaction as it occurred, i.e., it does not include a 
reaction that, had it occurred in a more serious form, might have caused death; 
3. 
is a persistent or significant disability or incapacity, i.e., the event causes a substantial 
disruption of a person’s ability to conduct normal life functions; 
4. 
requires, or prolongs in-patient hospitalization; 
5. 
is a congenital anomaly or birth defect; 
6. 
is an important medical event, based upon appropriate medical judgment, that may 
jeopardize the patient or subject or may require medical or surgical intervention to 
prevent one of the other outcomes defining serious. 
 
A “severe” AE does not necessarily meet the criteria for a “serious” AE. Serious adverse events 
are reported from the first dose of study medication to 21 days post-treatment.  
 
SAEs that are still ongoing at the end of the study period will be followed up to determine the 
final outcome. Any SAE that occurs after the study period and is considered to be possibly 
related (definitions will be used according to the WHO-UMC system; see: http://who-
umc.org/Graphics/24734.pdf) to the study treatment or study participation will be recorded and 
reported immediately. 
 
 


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6.1.6. Suspected unexpected serious adverse reactions 
A suspected unexpected serious adverse reaction (SUSAR) is an unexpected adverse drug 
reaction which also meets the definition of serious adverse events. 
 
6.2. Methods of recording and assessing adverse events 
Patients will be kept for observation for at least 3 hours following each morning treatment for 
any acute AEs. During the reporting period, any unfavorable changes in the subject’s condition 
will be recorded as adverse events, whether reported by the subject or observed by the 
investigator. In case of any abnormal finding, the local study physician will perform a full clinical 
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 be also interviewed by a nurse and/or a physician about the occurrence 
of AEs 24 hours after treatment. 
Information on all AEs (onset, duration, intensity, seriousness and causality) will be 
immediately entered in the appropriate AE module of the CRF which is considered as a source 
document. For all AEs, sufficient information will be pursued and/or obtained so as to permit i) 
an adequate determination of the seriousness of the event (i.e. whether the event should be 
classified as a SAE); ii) an assessment of the casual relationship between the AE and the 
study treatments (i.e. whether the event should be classified as an adverse drug reaction); and 
iii) an assessment of intensity of AEs by the study physician. 
 
All SAE, unexpected adverse drug reactions, or SUSARs must be reported as described in 
Section 6.3.  
 
6.3. Reporting of serious adverse events 
Any study-related unanticipated problem posing risk of harm to subjects or others, and any 
type of serious adverse event, will be reported (within 24h between site’s knowledge about the 
event and notification) to  
 
Prof. Dr. Jennifer Keiser (principal investigator) 
Swiss Tropical and Public Health Institute,  
Tel.: +41 61 284-8218 
Fax: +41 61 284-8105 
E-mail: jennifer.keiser@swisstph.ch 


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Within the following 48 hours, the local co-investigator must provide to study sponsor-
investigator further information on the serious adverse effect or the unanticipated problem in 
the form of a written narrative. This should include a copy of a completed SAE form, and any 
other diagnostic information that will assist the understanding of the event. In exceptional 
circumstances, a serious adverse event may be reported by telephone. In these cases, a 
written report must be sent immediately thereafter by fax or e-mail. Names, addresses and 
telephone for serious adverse event reporting will be included in the trial-specific SAE form. 
Relevant pages from the CRF may be provided in parallel (e.g., medical history, concomitant 
medications).  
 
6.4. Safety reporting to Health Authorities and Ethics Committees 
The sponsor-investigator will send appropriate safety notifications to Health Authorities in 
accordance with applicable laws and regulations. Additionally, this information will be provided 
to the ‘Ethik Kommission Nordwest- und Zentralschweiz’ (EKNZ, Switzerland) and the ethic 
committee of Lao PDR according to national rules. Fatal or life-threatening serious adverse 
events or SUSARs will be reported within 24 hours (between sponsor-investigator’s knowledge 
about the event and notification) followed by a complete report within 7 additional calendar 
days. Other serious adverse events and SUSARs that are not fatal or life-threatening will be 
filed as soon as possible but no later than 14 days after first knowledge by the sponsor-
investigator. 
 
7. Statistics 
7.1. Definition of primary endpoint 
Cure rate is the primary outcome measure of our study.  
7.2. Justification of number of trial subject 
(A) DF study: Since it is already known that moxidectin acts on S. stercoralis and the 
existence of a drug effect is known, the main aim of the study is the elucidation of the 
nature of the dose–response relationship. Computer simulations showed that with 30 
adults enrolled in each of the 7 study arms (0, 2, 4, 6, 8, 10, 12 mg) the dose response 
prediction model had a median precision (one half length of the 95%-confidence intervals) 
of 9%-points assuming associated true cure rates of 2.5%, 30%, 55%, 75% and 85%, 


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90%, 95% and a loss to follow up of 10%. The sample size is also in line with the 
recommendations from Klingenberg et al. 2009 [38]. 
 
DF study - PK sampling: The suggested sample size of 15 participants per study arm is 
sufficiently high to determine the key PK parameters, considering that PK variability is 
low. A low PK variability is a reasonable assumption when dealing with adults.  
 
(B) Non-inferiority moxidectin versus ivermectin: The main hypothesis of this trial is that an 8 
mg dose of moxidectin is non-inferior against S. stercoralis compared to the standard of 
care therapy (ivermectin). We assume a similar true CRs for moxidectin and ivermectin 
of 89% [15]. The sample size determination revealed, that we need 154 participants in 
each trial arm to demonstrate non-inferiority of moxidectin with a non-inferiority margin of 
10%-points with 80 power at the 95% confidence interval (equivalent to the 97.5% lower 
confidence bound). To account for an expected loss to follow-up of 10%, we target to 
enroll 175+175 = 350 participants. 
 
7.3. Description of statistical methods 
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 worm-positive adults 
at baseline who become worm-negative after treatment. LPG will be assessed by calculating 
the mean of the larvae counts from the three duplicate Baermann assays and relate this value 
to the mean weighted amount of stool sample. The LRR will be calculated (LRR = (1-(mean at 
follow-up/mean at baseline))*100).  
 
AEs will be evaluated descriptively as the difference of proportion reporting adverse events 
before and after treatment.  
 
Trial A: 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.  
Noncompartmental and nonlinear mixed-effects (NLME) modeling will be used to determine 
pharmacokinetic parameters.  
 
On the basis of the LC-MS/MS measurements, the following PK parameters for plasma, whole 
blood and capillary blood will be calculated:  
 
Cmax 
maximal plasma concentration 


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 
tmax 
time to reach Cmax 
 
AUC area under the curve, from 0 to 24h and 0 to inf. 
 
t1/2 
elimination half-life 
Cmax and tmax will be observed values derived from the plasma concentration time profile. AUC 
and t1/2 will calculated with the software WinNonlin (Version 5.2, Pharsight Corporation, USA) 
using compartmental analysis. The elimination half-life will be estimated by the equation: t1/2 = 
ln2/, where  will be determined by performing a regression of the natural logarithm of the 
concentration values during the elimination period.  
 
Trial B: The non-inferiority margin is set to 10%-points, i.e. if the lower bound of the 95% CI of 
the differences in cure rates is greater than -0.1 we conclude that moxidectin is non-inferior to 
ivermectin. The 95% confidence interval of the differences in CRs will be estimated using the 
standard formula: 
CI = (CRmox – CRiver) +/- Za/2 * (SEmox2 + SEiver2).  
 
Questionnaires on physical functioning and treatment satisfaction will be evaluated by creating 
summary scores by summing up and transforming the single question scores according to the 
following formula: [(actual raw score-lowest possible raw score)/(possible raw score 
range)]*100 [39]. 
 
8. Duties of the investigator 
8.1. Investigator’s confirmation 
This trial will be conducted in accordance with the protocol, International Conference on 
Harmonisation Good Clinical Practice E6 (ICH-GCP E6 (R2)) and the current version of the 
Helsinki Declaration. 
All protocol modifications must be documented in writing and implemented only with ethical 
approval. A protocol amendment can be initiated by either the sponsor-investigator or any 
investigator. The investigator will provide the reasons for the proposed amendment in writing 
and will discuss with the Sponsor-Investigator. Any protocol amendment must be approved 
and signed by the Sponsor-investigator and must be submitted to the appropriate Independent 
Ethics Committee (IEC) for evaluation and approval, in accordance with local requirements, 
and to regulatory agencies if required. Approval by IEC must be received before any changes 
can be implemented, except for changes necessary to eliminate an immediate hazard to trial 
subjects, or when the change involves only logistical or administrative aspects of the trial, e.g. 
change of telephone number(s). 


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8.2. Damage coverage 
A general liability insurance of the Swiss TPH is in place (Winterthur Police Nr. 4746321). 
Clinical trial compensation insurance is set up with the LAO-VIET insurance company (Policy 
021805872). Another policy will be issue in Cambodia. 
8.3. Project management 
The trial team will include the PI (Prof. Jennifer Keiser), a co-investigator and physician (Dr. 
Somphou Sayasonein Laos, Dr. Virak Khieu in Cambodia), a co-investigator (Dr. Daniela 
Hofmann), a trial statistician (Dr. Jan Hattendorf) and laboratory technicians. Prof. Jennifer 
Keiser, Dr. Somphou Sayasone, Dr. Daniela Hofmann will be responsible for staff 
management, communication with the collaborative group, recruitment monitoring, data 
management, safety reporting, analysis, report writing and dissemination of the trial results. 
Dr. Somphou Sayasone has the main medical responsibility and is responsible for supervision 
of the lab- and field technicians, staff management, recruitment monitoring, supply of the 
material, contact to the local authorities and participating institutions. 
The investigator team is responsible for ensuring that the protocol is strictly followed. The 
investigator should not make any changes without the agreement of the principal investigator 
and the co-investigators, except when necessary to eliminate an apparent immediate hazard 
or danger to a study participant. The investigator will work according to the protocol and GCP. 
The investigator may take any steps judged necessary to protect the safety of the participants, 
whether specified in the protocol or not. Any such steps must be documented. During the 
treatment the records are maintained by the responsible medical doctor. All entries have to be 
made clearly readable with a pen. The investigator must be thoroughly familiar with the 
properties, effects and safety of the investigational pharmaceutical product. 
 
9. Ethical considerations 
9.1. Independent Ethics Committee (IEC) 
The study will be submitted for approval by the institutional research commission of the Swiss 
TPH and the ethical committees of Switzerland, Laos and Cambodia. The study will be 
undertaken in accordance with the Declaration of Helsinki and good clinical practice (GCP E6 
(R2)). 


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9.2. Evaluation of the risk-benefit ratio 
Moxidectin is a well-known, FDA-approved drug against onchocerciasis and has little and 
mainly mild adverse events (headache, abdominal pain etc.). All community members enrolled 
in the study will benefit from a clinical examination and a treatment against STHs. All 
participating subjects remaining positive for S. stercoralis will be treated with ivermectin 
(according to WHO recommendations). 
9.3. Subject information and consent 
Community meetings allowing for open exchange will be organized in every study locality 
where a prescreening for identification of positive cases is to be conducted. The purpose and 
procedures, the benefits and risks of the study will be explained in order to make sure that all 
community members are at the same level in terms of information. All participants will be 
individually informed about benefits and risk associated to the trial. They will have sufficient 
time for reflection of their own participation.  
All eligible adults (≥18, <66) will be asked to sign a written informed consent sheet. They will 
have sufficient time for reflection of their own participation. They will then be asked to sign a 
written informed consent sheet. In case the person is illiterate, an impartial witness that can 
read and write has to sign the consent and the illiterate participant to give a thumb print.  
Information sheets are printed in English Lao and Khmer and will additionally be verbally 
translated into local languages during community meetings. To all participants a signed copy 
of the informed consent form will be given. Participation is voluntary and all participants have 
the right to withdraw from the study at any given point in time with no further obligations. 
Participation itself will not be awarded with compensation. However, transport and meals will 
be covered and free treatment of all diagnosed worms will be provided.  
9.4. Subject confidentiality 
The obtained data will be handled strictly confidentially. Only members of the study team will 
have access to the data.  
Screened patients will be listed in a confidential “subject screening log”. Enrolled patients will 
be listed in a confidential “subject enrolment log” and attributed a unique study number; this 
document will constitute the only source to decode the pseudonymized data and will only be 
accessible to the local principal investigator. Data analysis will be conducted with 
pseudonymised data and reporting of findings will be fully anonymised; personal data will be 
coded for data analysis. No names will be published at any time, and published reports will not 
allow for identification of single subjects. Confidentiality and anonymity will be ensured 


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throughout the entire research project. All databases will be password secured. Subject-
specific information may be provided to other appropriate medical personnel only with the 
subject’s permission. 
The investigators have all been trained in GCP. None of the investigators declare to have any 
conflicts of interest. 
9.5. Subjects requiring particular protection 
This study will be carried out in adults, since S. stercoralis infection occurs often in adults; 
hence this age group is at high risk of infection. Pharmacokinetic, dose-finding and non-
inferiority studies have not been conducted to date in this population. Our trial will provide more 
evidence and pave the further way for a safe and effective treatment of strongyloides infections 
in adults. 
9.6. Other aspects 
We will include one group of adults treated with placebo in each of the arms. However, this 
group will be treated with a standard treatment of a single dose ivermectin (200 µg/kg) at the 
end of the study (already 3-4 weeks later); hence this does not cause any medical concern. 
Considering all security measures (clinical, physical and biochemical exams) set up for 
inclusion of trial participants, any person showing an unfavorable medical condition will not be 
included in the trial. Hence we believe that a treatment delay of 3-4 weeks is not expected to 
cause any problem. Of note, populations at risk are in general treated only in yearly intervals 
to reduce morbidity from chronic infections within MDA campaigns of national control 
programs. 
 
10. Data management 
The investigators are responsible for an adequate data quality. Prior to the initiation of the 
study, a short investigators meeting will be held with the investigators and their study 
coordinators and a member of the Swiss TPH. This meeting will include a detailed discussion 
of the protocol, performance of study procedures, CRF completion, specimen collection and 
diagnostic methods. 
10.1. Data collection 
The data produced from this research project will fall into the following categories:  


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1. Eggs/Larvae counts of hookworm, Ascaris lumbricoides and Trichuris trichiura and S. 
stercoralis found in participants’ stool, soil or water samples using either the Kato-Katz 
or the Baermann technique before (baseline; stool, soil, water) and after (follow-up; 
stool) treatment.  
2. Personal information such as name, age and gender of trial participants. 
3. Anthropometric and clinical characteristics of the trial participants collected using the 
study’s CRF such as weight, height, blood pressure, temperature, any abnormal 
medical condition or chronic disease. 
4. Number and type of adverse events registered in the CRF and actively probed for 3 
and 24 hours after treatment. The same data will be collected during the collection of 
the follow-up, 28 days after treatment. 
5. Pharmacokinetic parameters such as Cmax, AUC, or tmax analyzed from capillary or 
venous blood sampling at 0, 2, 4, 8, 24, and 72 hours, 7 and 28 days post dosing or in 
between 0 and 28 days post dosing. 
6. Questionnaire: Record of the socioeconomic data of each participant’s household  
Data from categories 1-5 will be both paper-captured and directly into tablets using CommCare 
HQ (Digmagi, Inc., Cambridge, MA). CommCare HQ is a routine data management system 
ensuring complete, consistent and reliable data entry. For quality assurance error, range and 
consistency checks will assessed. 15% of data will be controlled by standard operating 
procedure, any discrepancies will be corrected by consulting the hard copy. If more than 1% 
of the double entered data display discrepancies, all data in categories 2-4 will be double 
entered by two independent people for quality assurance and verified as described.  
Data entered into CommCare HQ databases will only be accessible to authorized personnel 
directly involved with the study by use of a password. It will directly be saved on the personal, 
password-protected laptop of one of the Co-PIs and uploaded to a server hosted at Swiss 
TPH, Basel. Data in category 1-4 will be saved both in .xlsx and .csv. 
Data from categories 6 will be captured by software only. All categories will be merged into a 
single master filed saved in .xlsx and .csv. Data will then be analyzed as described in section 
7. PK parameters (category 5) derived from analyzing micro blood and whole blood samples 
will be merged and saved as a .xlsx, .txt or/ and .m file.  
10.2. Data handling and definition of source data - data entered directly in the 
Case Report Form  
Source Data are the clinical findings and observations, laboratory data maintained at the study 
site. Source data are contained in source documents. Local authorities are allowed to access 


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the source data. Data will be entered directly into the case report forms. The CRF is considered 
as a source document.  
 
A CRF will be completed for each subject enrolled into the clinical study. The investigators will 
review, and approve each completed CRF. The study CRF is the primary data collection 
instrument for the study. All data requested on the CRF must be recorded. All missing data 
must be explained. If a space on the CRF is left blank because the procedure was not done or 
the question was not asked “N/D” will be entered. If the item is not applicable to the individual 
case “N/A” will be written. All entries will be printed in black ink. All corrections must be initialed 
and dated.  
 
The study site (National institute of Laos) will retain a copy of the CRF to ensure that local 
collaborators can provide access to the source documents to a monitor, auditor, or regulatory 
agency while a copy of the CRF will be taken to Swiss TPH. 
Digital copies along with the databases will be transferred to the Swiss TPH after a Material 
Transfer Agreement has been signed by both the Swiss TPH and National institute of Laos 
(see Appendix). All data is expected to not exceed 5 GB. 
 
10.3. Definition of reference language – translation of study documents  
- Protocol: Master document in English, all further language versions are translations thereof. 
- CRF: Master document in English, all further language versions are translations thereof. 
- ICF: Master document in English, all further language versions are translations thereof. 
 
10.4. Storage and preservation 
After the study has been completed all samples will be destroyed. Data and related material 
will be preserved for a minimum of 15 years to enable understanding of what was done, how 
and why, which allow the work to be assessed retrospectively and repeated if necessary. 
Essential infrastructure such as lockable cabinets for safe storage of hardcopy data will be 
made available. Storage and backup will be in three places: personal password-protected 
laptops of Jennifer Keiser, Daniela Hofmann, Virak Khieu and Somphou Sayasone, Swiss TPH 
shared server and SWITCHdrive (a cloud storage supported by University of Basel). To the 
shared server and SWITCH drive only the above mentioned study team has access. Electronic 
data files and archiving conditions will be made strictly confidential by password protection. 
 


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11. Quality control and quality assurance 
11.1. Monitoring and auditing 
We will work with a locally based monitor. He/she will conduct site visits to the investigational 
facilities for the purpose of monitoring the study. Details on scope and frequency of monitoring 
activities will be described in a separate monitoring plan. The investigator will permit them 
access to study documentation and the clinical supplies dispensing and storage area. 
Monitoring observations and findings will be documented and communicated to appropriate 
study personnel and management. A corrective and preventative action plan will be requested 
and documented in response to any significant deviation. No sponsor initiated audits are 
foreseen, but audits and inspections may be conducted by the local regulatory authorities or 
ethics committees and ethics committees. The investigator agrees to allow inspectors from 
regulatory agencies to review records and is encouraged to assist the inspectors in their duties, 
if requested. 
11.2. Data and safety monitoring board (WHO) / data monitoring committee 
(EU/FDA) 
In our study no data and safety monitoring board will be established, since we work with well-
known drugs in a small sample size and using a single dose treatment. However, advisors will 
be informed regularly and the findings discussed.  
 
12. Dissemination of results and publication 
The final results of this study will be published in a scientific journal and presented at scientific 
conferences. The European Research Council and the Adiuvare Foundation will be 
acknowledged as study funder. All results from this investigation are considered confidential 
and shall not be made available to any third part by any member of the investigating team 
before publication. A study report will be shared with the local ethics committees and the 
national regulatory authorities. 


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32. 
Korth-Bradley, J.M., et al., Relative Bioavailability of Liquid and Tablet Formulations of 
the Antiparasitic Moxidectin. Clinical Pharmacology in Drug Development, 2012. 1(1): 
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33. 
Campbell, S.J., et al., A Critical Appraisal of Control Strategies for Soil-Transmitted 
Helminths. Trends Parasitol, 2016. 32(2): p. 97-107. 
34. 
Strunz, E.C., et al., Water, sanitation, hygiene, and soil-transmitted helminth infection: 
a systematic review and meta-analysis. PLoS Med, 2014. 11(3): p. e1001620. 
35. 
Kepha, S., et al., Impact of single annual treatment and four-monthly treatment for 
hookworm and Ascaris lumbricoides, and factors associated with residual infection 
among Kenyan school children. Infect Dis Poverty, 2017. 6(1): p. 30. 
36. 
Coulibaly, J.T., et al., Efficacy and safety of praziquantel in preschool-aged and school-
aged children infected with Schistosoma mansoni: a randomised controlled, parallel-
group, dose-ranging, phase 2 trial. Lancet Glob Health, 2017. 5(7): p. e688-e698. 
37. 
Awadzi, K., et al., A randomized, single-ascending-dose, ivermectin-controlled, double-
blind study of moxidectin in Onchocerca volvulus infection. PLoS Negl Trop Dis, 2014. 
8(6): p. e2953. 
38. 
Klingenberg, B., Proof of concept and dose estimation with binary responses under 
model uncertainty. Stat Med, 2009. 28(2): p. 274-92. 
39. 
Furst, T., et al., Questionnaire-based approach to assess schoolchildren's physical 
fitness and its potential role in exploring the putative impact of helminth and 
Plasmodium spp. infections in Cote d'Ivoire. Parasit Vectors, 2011. 4: p. 116. 
 
 
 
 
 
 


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Appendix 1 
 
Material Transfer Agreement 
Between 
 
National Institute of Public Health, Vientiane, Laos 
(Hereinafter referred to as PROVIDER) 
 
And 
 
Swiss Tropical and Public Health Institute 
Socinstrasse 57, CH-4051 Basel 
(Hereinafter referred to as RECIPIENT) 
 
Preamble 
PROVIDER’s has sampled Original Material in the course of or academic research. 
RECIPIENT wishes to conduct non-commercial research with MATERIAL. 
PROVIDER is willing to provide the Original Material to RECIPIENT under the following terms and 
conditions: 
1. 
Definitions: 
“Recipient’s Scientist” is Prof. Jennifer Keiser 
„Original Material“shall mean the following biological material and Data (s): 
- 
Blood samples of PK participants  
- 
CRF data of study participants 
 
 
“MATERIAL” shall mean Original Material and Progeny and Unmodified Derivatives thereof as well 
as any accompanying information. 
 
“Progeny” shall mean unmodified descendant from the MATERIAL, such as cell from cell. 
 
“Unmodified Derivatives” shall mean substances created by RECIPIENT which constitute an 
unmodified functional subunit or product expressed by the Original Material. 
 
“Modifications” shall mean substances created by RECIPIENT which contain/incorporate the 
MATERIAL. 
2. 
The MATERIAL is, regarding the inherent intellectual property rights, the property of PROVIDER 
and is to be used by RECIPIENT solely for non-commercial research purposes at RECIPIENT's 
institution and only under the direction of the Recipient's Scientist. The research to be conducted 
by Recipient's Scientist is restricted to the project described in the study protocol.  
3. 
The Recipient's Scientist agrees not to transfer the MATERIAL to anyone who does not work under 
his or her direct supervision at RECIPIENT's institution without the prior written consent of 
PROVIDER. 
4. 
(a) PROVIDER retains ownership of the MATERIAL, including any MATERIAL contained or 
incorporated in Modifications. 


StrongMoxi, Protocol, v2.2, 01.07.2020 
 
Page 44 of 45 
 
 
(b) RECIPIENT retains ownership of: (i) Modifications (except that, PROVIDER retains ownership 
rights to the MATERIAL included therein) and (ii) those substances created through the use of the 
MATERIAL or Modifications, but which are not Progeny, Unmodified Derivatives or Modifications. 
5. 
Except as expressly provided in this Agreement, no rights are provided to RECIPIENT under any 
patents, patent applications, trade secrets or other proprietary rights of PROVIDER. In particular, 
no rights are provided to use the MATERIAL or Modifications and any related patents of PROVIDER 
for profit making or commercial purposes, such as sale of the MATERIAL or Modifications, use in 
manufacturing, provision of a service to a third party in exchange for consideration, or use in 
research or consulting for a for profit entity under which that entity obtains rights to research 
results. 
6. 
Any MATERIAL delivered pursuant to this Agreement is understood to be experimental in nature 
and may have hazardous properties. PROVIDER MAKES NO REPRESENTATIONS AND EXTENDS NO 
WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED. THERE ARE NO EXPRESS OR IMPLIED 
WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR THAT THE USE 
OF THE MATERIAL WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER 
PROPRIETARY RIGHTS. 
7. 
Except to the extent prohibited by law, RECIPIENT assumes all liability for damages that may arise 
from its use, storage or disposal of the MATERIAL. PROVIDER will not be liable to RECIPIENT for 
any loss, claim or demand made by RECIPIENT, or made against RECIPIENT by any other party, due 
to or arising from the use of the MATERIAL by RECIPIENT, except when caused by the gross 
negligence or willful misconduct of PROVIDER. 
8. 
Recipient's Scientist agrees to provide appropriate acknowledgment of the source of the 
MATERIAL in all publications and agrees to send PROVIDER a copy of any such publications. 
9. 
RECIPIENT acknowledges that the MATERIAL is human material which may underlay specific 
legislations of privacy protection. RECIPIENT agrees (i) to use the MATERIAL in compliance with all 
applicable statutes and regulations including, for example, all applicable data privacy laws, (ii) to 
use the MATERIAL in accordance with patient consent, (iii) to secure that if he is informed by 
PROVIDER that a patient withdraws his or her consent to use his or her material, any such 
MATERIAL which is in RECIPIENT’s possession is immediately destroyed and not longer used.  
11. The Research using the MATERIAL shall last not longer than 10 years, unless the Agreement is 
formally extended. It is the responsibility of the RECIPIENT to seek such a prolongation. In the 
event RECIPIENT is not using and does not intend to use the MATERIAL or as soon as the Research 
will be concluded or this Agreement will expire or be terminated for whatever reason, the 
RECIPIENT is obliged to return to PROVIDER, if possible, or to destroy with required care, all 
MATERIAL. 
12. The MATERIAL is provided without a fee. 
13. The effective date of this Agreement is the date of the last required signature obtained. 
14. This Agreement shall be construed and interpreted in accordance with the laws of Switzerland. 
Place of jurisdiction shall be Basel (Switzerland). 
 
 
 
 
 
In Witness Whereof, the parties hereto have caused this Agreement to be executed on the 
dates set forth below by their duly authorized representatives. 


StrongMoxi, Protocol, v2.2, 01.07.2020 
 
Page 45 of 45 
 
 
For PROVIDER 
 
 
Date: _______________________ 
 
 
 
 
 
By: 
___________________________                                  ______________________ 
 
Dr. MD Somphou Sayasone                                             (Signature) 
           National Institute of Public Health, Vientiane, Laos 
 
 
 
 
For RECIPIENT 
 
 
Date: _______________________ 
 
 
 
 
 
By: 
___________________________     
                ______________________ 
 
Prof. Jennifer Keiser  
                                     (Signature) 
 
 
 
Date: _______________________ 
 
 
 
 
 
By: 
___________________________                                  ______________________ 
          Matthias Schmid Huberty, administrative director Swiss TPH              (Signature)