Efficacy and Safety of Moxidectin-albendazole Combination for Trichuris Trichiura Infections in School-aged Children: a Double-blind Randomised Controlled Superiority Trial
Phase: PHASE3
Conditions: Trichuriasis, Ascariasis, Hookworm Infections
Sponsor: Jennifer Keiser

Efficacy and safety of moxidectin-albendazole combination for 
Trichuris trichiura infections in school-aged children: a double-blind 
randomised controlled superiority trial 
 
NCT Number: NCT06188715 
 
Document date: 02 April 2024 

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Efficacy and safety of moxidectin-albendazole combination for Trichuris 
trichiura infections in school-aged children: a double-blind randomised 
controlled superiority trial 
Document Version 
1 
Document Date 
02 April 2024 
Sponsor Contact 
Prof. Dr. Jennifer Keiser, 
Swiss Tropical and Public Health Institute, 
Tel.: +41 61 284 82 18 
Fax: +41 61 284 81 05 
E-mail: jennifer.keiser@unibas.ch 
Principle Investigator 
Prof. Dr. Jennifer Keiser, 
Swiss Tropical and Public Health Institute, 
Tel.: +41 61 284 82 18 
Fax: +41 61 284 81 05 
E-mail: jennifer.keiser@unibas.ch 
Funding Agency 
Swiss National Science Foundation 

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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), Allschwil, 
Switzerland 
Unit head 
Principal 
Investigator 
MSc 
Said Mohammed 
Ali 
Public Health 
Laboratory Ivo de 
Carneri (PHL-IdC) 
Foundation, Pemba, 
Tanzania 
CEO 
Co-PI 
Dr. 
Ibrahim Said 
Mohammed 
Ministry of Health, 
Pemba, Tanzania 
Project leader, 
physician 
Study physician 
MSc 
Viviane Sprecher 
Swiss TPH, 
Allschwil, 
Switzerland 
Doctoral student 
Co-PI, 
Study pharmacist 
MSc 
Annina Schnoz 
Swiss TPH, 
Allschwil, 
Switzerland 
Doctoral student 
Co-PI 
Dr. 
Jan Hattendorf 
Swiss TPH, 
Allschwil, 
Switzerland 
Project leader 
Statistician 

moxiped_protocol_v1.1_20240402 
II.
Signatures
Principal investigator 
Signature & 
Date 
Name 
Jennifer Keiser 
Title 
Prof. Dr. 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Kreuzstrasse 2 
CH-4123 Allschwil, Switzerland 
Phone 
+41 61 284 82 18
Statistician 
Signature & 
Date 
Name 
Jan Hattendorf 
Title 
Dr. 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Epidemiology and Public Health 
Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 
CH-4123 Allschwil, Switzerland 
Phone 
+41 61 284 81 93
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 fulfil 
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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02-Apr-2024 | 16:39:51 CET
02-Apr-2024 | 17:26:00 CET

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Co-Principal investigator 
Signature & 
Date 
Name 
Said Mohammed Ali 
Title 
MSc 
Institution 
Public Health Laboratory Ivo de Carneri 
Address 
P.O. Box 122 Wawi, Chake Chake, 
Pemba, Tanzania 
Phone 
+255 24 245 20 03
Study physician 
Signature & 
Date 
Name 
Ibrahim Said Mohammed 
Title 
Dr. 
Institution 
Ministry of Health Pemba 
Address 
P.O. Box 122 Wawi, Chake Chake,
Pemba, Tanzania 
Phone 
+255 77 253 05 31
Co-Principal investigator, Study pharmacist
Signature & 
Date 
02-Apr-2024 | 17:54:08 CET
Name 
Viviane Sprecher 
Title 
MSc 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Kreuzstrasse 2 
CH-4123 Allschwil, Switzerland 
Phone 
+41 61 284 92 44
Co-Principal investigator 
Signature & 
Date 
02-Apr-2024 | 17:46:44 CET
Name 
Annina Schnoz 
Title 
MSc 
Institution 
Swiss Tropical and Public Health Institute 
Address 
Department of Medical Parasitology and Infection Biology 
Swiss Tropical and Public Health Institute, Kreuzstrasse 2 
CH-4123 Allschwil, Switzerland 
Phone 
+41 61 284 92 86

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Table of contents 
1.
General information ........................................................................................................................ 2
2.
Background information ................................................................................................................ 13
3.
Trial objective and purpose ........................................................................................................... 14
4.
Methodology ................................................................................................................................. 15
4.1
Primary and secondary endpoint ........................................................................................... 15
4.2
Trial design ............................................................................................................................ 15
4.3
Procedures ............................................................................................................................. 16
4.3.1
Diagnosis ....................................................................................................................... 16
4.3.2
FECPAKG2 ................................................................................................................... 16
4.3.3
Clinical examination ...................................................................................................... 17
4.3.4
Treatment of participants ............................................................................................... 17
4.3.5
Pharmacokinetic analysis .............................................................................................. 18
4.3.6
Safety assessment .......................................................................................................... 19
4.3.7
Efficacy assessment ....................................................................................................... 19
4.4
Measure to minimise bias ...................................................................................................... 19
4.5
Study duration and duration of participation ......................................................................... 19
5.
Selection of trial participants ......................................................................................................... 20
5.1
Recruitment ........................................................................................................................... 20
5.2
Inclusion criteria .................................................................................................................... 20
5.3
Exclusion criteria ................................................................................................................... 21
5.4
Criteria for discontinuation of trial ........................................................................................ 21
5.5
Concomitant medication ........................................................................................................ 21
6.
Safety assessments ........................................................................................................................ 21
6.1
Adverse event definitions ...................................................................................................... 22
6.1.1
Severity grading............................................................................................................. 22
6.1.2
Relatedness .................................................................................................................... 23
6.1.3
Expectedness ................................................................................................................. 23
6.1.4
Serious adverse events ................................................................................................... 23
6.1.5
Suspected unexpected serious adverse reactions ........................................................... 24

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6.2 
Methods of recording and assessing adverse events ............................................................. 24 
6.3 
Reporting of serious adverse events ...................................................................................... 25 
6.4 
Safety reporting to Health Authorities, Ethics Committees and other third parties .............. 25 
6.5 
Rescue medication strategy ................................................................................................... 26 
7. 
Data management and data quality control ................................................................................... 26 
7.1 
Source data ............................................................................................................................ 26 
7.2 
Data collection and documentation ....................................................................................... 26 
7.3 
Ethical, legal and security issues ........................................................................................... 27 
7.4 
Data storage and preservation ............................................................................................... 27 
7.5 
Study documents: translations – reference language ............................................................. 28 
8. 
Statistics......................................................................................................................................... 28 
8.1 
Definition of primary endpoint .............................................................................................. 28 
8.2 
Justification of number of trial participants ........................................................................... 28 
8.3 
Description of statistical methods ......................................................................................... 28 
9. 
Duties of the investigator............................................................................................................... 30 
9.1 
Investigator’s confirmation ................................................................................................... 30 
9.2 
Damage coverage .................................................................................................................. 30 
9.3 
Project management .............................................................................................................. 30 
10. 
Ethical considerations ................................................................................................................ 31 
10.1 
Independent Ethics Committee (IEC) ................................................................................... 31 
10.2 
Evaluation of the risk-benefit ratio ........................................................................................ 31 
10.3 
Participant information and consent ...................................................................................... 31 
10.4 
Participants requiring particular protection ........................................................................... 32 
11. 
Quality control and quality assurance ....................................................................................... 32 
11.1 
Monitoring and auditing ........................................................................................................ 32 
11.2 
Data and safety monitoring board (WHO) / data monitoring committee (EU/FDA) ............ 32 
12. 
Funding ...................................................................................................................................... 33 
13. 
Dissemination of results and publication .................................................................................. 33 
14. 
References ................................................................................................................................. 34 

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III. 
Abbreviations 
AE 
Adverse event 
CI 
Confidence interval 
CR 
Cure rate 
CRF 
Case report form 
EKNZ 
Ethikkommission Nordwest- und Zentralschweiz 
EPG 
Eggs per gram 
ERR 
Egg reduction rate 
EU 
European Union 
FDA 
Food & Drug Administration 
GCP 
Good clinical practice 
Hb 
Haemoglobin 
ICF 
Informed consent form 
ICH 
International 
council 
for 
harmonization 
of 
technical 
requirements 
for 
pharmaceuticals for human use 
IEC 
Independent ethics committee 
MDA 
Mass drug administration 
NLME 
nonlinear mixed-effects 
PC 
Preventive chemotherapy 
PHL-IdC 
Public Health Laboratory Ivo de Carneri 
PI 
Principal investigator 
PK 
Pharmacokinetics 
SAC 
School-aged children 
SAE 
Serious adverse event 
SNSF 
Swiss National Science Foundation 
STH 
Soil-transmitted helminths 
SUSAR 
Suspected unexpected serious adverse reaction 
Swiss TPH 
Swiss Tropical and Public Health Institute 
WHO 
World Health Organization 

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IV. 
Synopsis 
 
Sponsor/Sponsor-
Investigator 
Prof. Dr. Jennifer Keiser 
Study title 
Efficacy and safety of moxidectin-albendazole combination for 
Trichuris trichiura infections in school-aged children: a double-blind 
randomised controlled superiority trial 
Short title 
Moxidectin-albendazole combination for Trichuris trichiura–infected 
children 
Study acronym 
Moxiped 
Protocol version and date 
v1, 02 April 2024 
Trial registration 
Registered on https://www.clinicaltrials.gov/ (NCT06188715) 
Clinical phase 
Phase 3 trial 
Sample size 
210 participants 
Indication 
Trichuris trichiura infection (eggs in stool) 
Investigational and 
reference treatment 
Moxidectin-albendazole combination 
Reference: albendazole and placebo 
Study rationale 
To provide evidence on the efficacy and safety of co-administered 
moxidectin and albendazole compared to albendazole monotherapy in 
school-aged children (SAC; aged 6-12 years) infected with T. trichiura. 
Additionally, to substantiate evidence on the safety profile of 
moxidectin-albendazole combination in this age group using a placebo 
(and albendazole) only arm. To date, this has only been established in 
adolescents (aged 16-18 years), who might present different symptoms 
or symptom severity compared with SAC. 
 
 

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Study objectives 
Our primary objective is to demonstrate superiority of 
a) Arm A: moxidectin (4 mg / 8 mg) & albendazole (400 mg) 
combination, 
compared to 
b) Arm B: albendazole (400 mg) 
in terms of cure rate (CR), assessed at 14-21 days post-treatment by 
quadruplicate Kato-Katz microscopy, in SAC (6-12 years) infected with 
T. trichiura. 
The secondary objectives of the trial are: 
a) to determine the T. trichiura egg reduction rates (ERRs) of 
treatments; 
b) to determine the CRs and ERRs of treatments against 
Ascaris lumbricoides and hookworm co-infection; 
c) to evaluate the safety and tolerability of the treatments; 
d) to characterize population pharmacokinetics (PK) of moxidectin 
in T. trichiura infected SAC. 
The exploratory objective of this trial is to assess the diagnostic 
performance of FECPAKG2. 
Study design 
Parallel randomised controlled superiority trial 
Study product / 
intervention 
Administration of a single oral dose of moxidectin (4 mg or 8 mg) and 
albendazole (400 mg) 
Comparator(s) 
Albendazole (400 mg), placebo 
Key inclusion / Exclusion 
criteria 
Inclusion: 
 
Individuals aged 6-12 years (confirmed by birth certificate or 
similar document); 
 
having 
given 
written 
informed 
consent 
signed 
by 
parents/caregivers and assent by participant; 
 
being able and willing to provide two stool samples at baseline 
and at follow-up assessment (14-21 days); 
 
having at least two out of four Kato-Katz slides positive for 
T. trichiura at baseline; 
 
being able and willing to be examined by a study physician 
before and after treatment. 

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Exclusion: 
 
presence or signs of major systemic illness, e.g. fever (temporal 
body temperature of >38.0°C), severe anaemia (haemoglobin 
level of <80 g/l); 
 
history of severe acute disease or unmanaged, severe chronic 
disease (i.e., condition is not as therapeutically controlled as 
necessary); 
 
use of anthelminthic drugs during study period; 
 
known allergy to study medication (i.e., moxidectin or 
albendazole); 
 
being prescribed or taking concomitantly medication with 
known contraindications or drug interactions with the study 
medication; 
 
pregnancy (female participants aged 10-12 years); 
 
concurrent participation in other clinical trials. 
Primary endpoints 
 
T. trichiura infection status of participants at 14-21 days post-
treatment assessed by quadruplicate Kato-Katz 
Secondary endpoints 
 
T. trichiura infection intensity of participants at 14-21 days 
post-treatment assessed by quadruplicate Kato-Katz 
 
A. lumbricoides and hookworm infection status and intensity of 
co-infected participants at 14-21 days post-treatment assessed 
by quadruplicate Kato-Katz 
 
Adverse events (AEs) 
 
Population PK parameters of moxidectin in T. trichiura infected 
SAC 
Exploratory endpoints 
Diagnostic characteristics of FECPAKG2 (infection intensity, 
sensitivity, and specificity) compared to Kato-Katz 
Interim analyses 
None 
Study duration 
2 months 
Schedule 
04/2024: of first participant in (planned) 
06/2024: of last participant out (planned) 

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Study centres 
T. trichiura endemic villages, Wete district, Pemba Island, Tanzania 
Measurements & 
procedures 
For the initial diagnosis and efficacy assessment at 14-21 days post-
treatment, two stool samples will be collected from each participant on 
two consecutive days. All stool samples will be examined for presence 
of T. trichiura, A. lumbricoides, and hookworm eggs with duplicate 
Kato-Katz thick smears assessed via bright-field microscopy. The 
medical history of the participants will be assessed with a standardised 
questionnaire, in addition to a clinical examination carried out by the 
study physician before treatment. All participants will be interviewed 
before treatment and at three and 24 hours and 14-21 days post-treatment 
for the occurrence of AEs. Any potential AEs happening between 3 
hours and the respective follow-up time points will be monitored by 
local healthcare workers and medical intervention provided if necessary. 
Each participant will be asked to provide a finger-prick blood sample for 
haemoglobin 
measurement 
at 
baseline. 
At 
the 
same 
time, 
anthropometric measurements (i.e. height, and weight) will be taken for 
all participants. In addition, female participants aged 10-12 years will be 
asked to provide a urine sample to determine pregnancy. 
To determine PK parameters of moxidectin, a subsample of 12 study 
participants per moxidectin dose (4 mg and 8 mg) will be asked to 
provide a maximum of 5 micro blood samples per participant using 
finger pricks at defined time points between 1 hour and 24 hours. 
Statistical analyses 
An available case analysis (full analysis set according to the intention to 
treat principles) will be performed, including all participants with 
primary endpoint data. Additionally, a per-protocol analysis will be 
conducted. CRs will be calculated as the percentage of egg-positive 
participants at baseline who become egg-negative after treatment. 
Differences in CRs (between treatment arms) will be analysed using 
logistic regression. 
Geometric and arithmetic mean egg counts will be calculated for the 
different treatment arms before and after treatment to assess the 
corresponding ERRs. Bootstrap resampling with 5,000 replicates will be 
used to calculate 95% confidence intervals (CIs) for ERRs and 
differences between ERRs. 

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AEs will be compiled into frequency tables and compared between 
treatment groups using descriptive summary statistics. 
With regard to population PK parameters, Cmax and tmax will be 
observed values, AUC and t1/2 will be calculated using nonlinear mixed-
effects (NLME) modelling with the WinNonlin software package. In 
addition, exploratory pharmacometric PK and exposure-response 
analyses may be performed with the Monolix or NONMEM software 
package. 
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 children 
This study will involve children aged 6-12 years, since an infection with 
T. trichiura occurs most often in children who are therefore the main 
target group of deworming campaigns. The main goal of the study is to 
evaluate for the first time the efficacy and safety of moxidectin-
albendazole in this age group. 
Recruitment procedure 
The trial will be conducted on Pemba Island, Tanzania. It will take place 
in areas with moderate to high T. trichiura endemicity (communities 
with a prevalence of ≥20%) identified from earlier studies and/or based 
on experience of the local collaborating team. 
Coverage of damages 
Winterthur Insurance, Policy No. 4746321; 
Pemba: National Insurance Cooperation of Tanzania LTD, Policy No. 
IMIS/GL/P/25/1/2024/771417 
Storage of data and 
samples for future 
research aims 
After the study has been completed, all samples will be destroyed. Case 
report forms and electronic source data will be kept for a minimum of 
15 years. 
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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2. Background information 
Trichuriasis is a parasitic disease caused by nematodes belonging to the group of soil-transmitted 
helminths (STH). It is estimated that around 400 million people harbour infections with 
Trichuris trichiura globally [1]. As it is the case for all STH infections, trichuriasis is mainly endemic 
in developing countries in tropical and subtropical regions, with highest burden among rural 
communities due to its link to poor sanitation [2]. 
Infection with T. trichiura occurs when ingesting embryonated eggs via soil-contaminated hands, 
drinking water or food. Having reached the small intestine, the eggs hatch realising the larvae. The 
larvae migrate directly into the cecum where they develop into adult worms and begin to oviposit. Eggs 
are excreted into the soil via the faeces, thereby closing the life cycle [3]. 
Acute symptoms of trichuriasis are generally mild or not apparent in infected individuals living in 
endemic areas [2, 4]. The main disease burden results from chronic infection and repeated re-infection, 
in which symptoms related to the location of adult worms such as abdominal pain may develop. Long-
term infection compromises the life of people by hampering their physical and mental development, 
limiting their work performance and overall quality of life [4]. 
The recent World Health Organization (WHO) road map for neglected tropical diseases targets STH 
infections for near to global elimination as a public health problem by 2030 [5]. One important 
intervention to achieve this is preventive chemotherapy (PC) [5-7]. The aim of PC is to reduce worm 
burden and hence morbidity in endemic populations by regular large-scale administration of 
anthelminthic drugs to high-risk groups, e.g. preschool-aged and school-aged children (SAC) [8, 9]. The 
frequency of such mass drug administration (MDA) depends on the local infection prevalence [8, 9]. 
At present, the benzimidazoles albendazole and mebendazole are the most widely used drugs for PC 
campaigns against STH infections [7, 10]. These drugs are characterized by high cure rates (CRs) against 
infections with Ascaris lumbricoides (>95%) and moderate CRs against hookworm infections (80%). 
However, at single oral doses suitable for MDA, these drugs have demonstrated unsatisfactory efficacy 
against T. trichiura infections [11, 12]. 
Therapies combining two or more drugs are widely advocated in different therapeutic areas. The 
advantages of multifactorial pharmacological treatment include the increase and broadening of efficacy 
over drugs being administered in monotherapy and the protection against the selection of drug 
resistance, and hence, a prolongation of the life-span of effective and available drugs [13-15]. In 2017, 
ivermectin in combination with albendazole for treatment of STH was added to the Essential Medicines 
List (EML) paving the way to further evaluate the efficacy of combination treatments among SAC and 
communities in a range of epidemiological settings [16]. 
Moxidectin, a macrocyclic lactone like ivermectin, has been approved by the United States Food & Drug 
Administration (FDA) for the treatment of onchocerciasis in 2018 in individuals aged ≥12 years [17]. 
The combination of moxidectin (at a dose of 8 mg) and albendazole has shown promising efficacy 

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against T. trichiura infections in adolescents and adults [18-20]. However, there is a need to explore 
whether moxidectin could reveal a benefit in the treatment of STH infections in SAC. A phase 1 trial 
determining safety and pharmacokinetics of moxidectin in children aged 4-11 years living in Ghana has 
recently been completed [21]. Based on the findings of this trial, it was recommended to administer 
single doses of 4 mg moxidectin to individuals aged <8 years and 8 mg to individuals aged ≥8 years. 
In this trial, we aim to evaluate if the recommended doses of moxidectin in combination with 
albendazole are a safe and efficacious treatment against T. trichiura infection in SAC on Pemba Island, 
Tanzania, and superior to albendazole monotherapy. Furthermore, given that the most commonly 
reported adverse events of moxidectin and albendazole correspond to the main symptoms of trichuriasis, 
a placebo only arm will be included to better define the safety profile of moxidectin-albendazole 
combination. To date, this has only been established in adolescents (aged 16-18 years), who might 
present different symptoms or symptom severity compared with SAC.[18] Finally, we re-assess 
pharmacokinetic (PK) parameters of moxidectin in SAC. The PK characterization of a drug is essential 
to understand the response of the human body to a drug and vice versa, especially in populations that 
physiologically differ from healthy adults. Physiological characteristics like mal- or undernutrition due 
to intestinal worms, such as T. trichiura, can potentially affect the PK of a drug [22, 23]. Age, sex, 
bodyweight but also the presence of certain enzymes in different populations are important contributors 
to the PK profile of a drug. Our study will be the first one to provide PK information on moxidectin in 
SAC with trichuriasis and thus guide optimal drug dosing in this high-risk population. 
 
3. Trial objective and purpose 
We designed a superiority trial to show that moxidectin-albendazole combination is superior compared 
to albendazole monotherapy in treating trichuriasis in individuals aged 6-12 years on Pemba Island, 
Tanzania. This study will provide further insights on the value of moxidectin-albendazole combination. 
Our data will support the development of moxidectin in children aged <12 years and its implementation 
in control programs. As recommended for new combination therapies, we assess superiority of the drug 
combination compared to standard-of-care monotherapy. In addition, we aim to substantiate evidence 
on the safety profile of moxidectin-albendazole combination in SAC using a placebo only arm. 
The primary objective is to demonstrate that co-administered moxidectin (4 mg / 8 mg) & albendazole 
(400 mg) is superior to albendazole (400 mg) monotherapy in terms of CR in T. trichiura-infected 
children aged 6-12 years assessed at 14-21 days post-treatment by quadruplicate Kato-Katz microscopy. 
The secondary objectives of the trial are: 
a) to determine the T. trichiura egg reduction rates (ERRs) of treatments; 
b) to determine the CRs and ERRs of treatments against A. lumbricoides and hookworm co-
infection; 
c) to evaluate the safety and tolerability of the treatments; 

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d) to characterize population PK of moxidectin in T. trichiura infected SAC. 
The exploratory objective of this trial is to assess the diagnostic performance of FECPAKG2. 
 
4. Methodology 
4.1 
Primary and secondary endpoint 
Primary endpoint: T. trichiura infection status of participants at 14-21 days post-treatment assessed 
by quadruplicate Kato-Katz. 
Secondary endpoints: 
 
T. trichiura infection intensity of participants at 14-21 days post-treatment assessed by 
quadruplicate Kato-Katz; 
 
A. lumbricoides and hookworm infection status and intensity of co-infected participants at 14-21 
days post-treatment assessed by quadruplicate Kato-Katz; 
 
Tolerability of treatments (adverse events (AEs)) at three and 24 hours and 14-21 days post-
treatment; 
 
Population PK parameters of moxidectin in T trichiura infected SAC. 
Exploratory endpoints: Diagnostic characteristics of FECPAKG2 (infection intensity, sensitivity, and 
specificity) compared to Kato-Katz. 
4.2 
Trial design 
A parallel randomised controlled superiority trial will be conducted with three treatment arms (Figure 
1). The study includes a baseline screening (day -30 to -1) and clinical baseline assessment (day 0) 
before treatment and post-treatment assessments for safety (day 0, 1 and 14 to 21) and efficacy (day 14 
to 21). It is designed as a parallel three-arm trial with 210 participants aged 6-12 years randomised to 
either moxidectin (4 mg for 6-7 year-olds and 8 mg for 8-12 year-olds) and albendazole (400 mg), 
moxidectin placebo and albendazole (400 mg), or moxidectin placebo and albendazole placebo, with an 
allocation ratio of 3:2:1 (i.e., 105:70:35). This trial will be conducted in communities in the Wete district 
on Pemba Island with high endemicity as identified in previous studies on T. trichiura. 
 

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Figure 1. Trial design and timeline. 
4.3 
Procedures 
4.3.1 
Diagnosis 
At baseline, all participants will be asked to provide two stool samples. From each stool specimen, 
duplicate Kato-Katz thick smears (41.7 mg each) [24] will be prepared and read under a microscope for 
eggs of T. trichiura, A. lumbricoides and hookworm by experienced technicians. Eggs per gram (EPG) 
will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and 
multiplying this number by a factor of six. For quality control of T. trichiura and A. lumbricoides egg 
counts, 10% of slides will be re-read by another laboratory technician. Results are considered correct if 
the following tolerance margin is not exceeded: (i) No difference in presence/absence of T. trichiura 
and A. lumbricoides (ii) egg counts are +/-10 eggs for counts ≤100 eggs or +/-20% for counts >100 eggs 
(for each species separately). In case discrepancies above the tolerance margin are noted in one or more 
slides, the respective 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. All microscopically analysed 
quadruplicate Kato-Katz thick smears will be destroyed after passing the quality control. The same 
diagnostic approach will be applied at 14-21 days after treatment (see section 4.3.7). 
4.3.2 
FECPAKG2 
Research on new diagnostic tools is necessary, since the currently recommended Kato-Katz technique 
has a low sensitivity for low STH infections and slides with hookworm eggs cannot be re-examined [25-
27]. Once moving towards transmission control and STH elimination, an increased sensitivity of the 
diagnostic method of choice is crucial [28]. Preferably, a diagnostic method that could potentially 

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replace Kato-Katz would be sensitive, specific, fast, simple, cost-effective and re-analysis could be 
conducted at any time. 
The aim of this exploratory objective within this this trial is the comparison of infection intensity, 
sensitivity, and specificity of the Kato-Katz technique with the novel diagnostic tool FECPAKG2 
(Techion). FECPAKG2 is an online, remote location, parasite diagnostic system used in veterinary 
medicine [29]. An image of the Kato-Katz slide is captured, stored offline on a computer, and can be 
uploaded onto a cloud once connected to the internet. Subsequently, specialists around the world can 
analyse the image at any time. Techion’s image capture devices are robust, reliable, versatile and cost 
effective [30]. Baseline quadruplicate Kato-Katz thick smears will be used to take images by 
FECPAKG2 after the slides have been read by technicians under the microscope. 
4.3.3 
Clinical examination 
A clinical examination of the study participants assessing general health, anthropometric parameters 
including height and weight as well as temperature using a non-contact infrared forehead thermometer 
(Braun No touch – NTF3000; Braun, Kronberg, Germany) will precede the treatment. Each participant 
will be asked to provide a finger-prick blood sample to measure haemoglobin (Hb) levels, which will 
be detected using a HemoCue analyzer (Hb 301 system, Angelholm, Sweden). In case of abnormal 
values, results from baseline clinical examination may be reported back to participants and their 
parents/caregivers during the trial period. To avoid accidental treatment of pregnant girls, all female 
participants aged 10-12 years will be asked to provide a urine sample to be subjected to a pregnancy 
RDT during clinical examination All trial participants will further be asked about existing clinical 
symptoms before drug administration using a standardised questionnaire. 
4.3.4 
Treatment of participants 
All eligible participants will be treated with the respective treatment regimen according to their treatment 
arm assigned by randomisation at day 0. Moxidectin tablets (2 mg) and appearance-matching placebo 
tablets will be obtained from Medicines Development for Global Health (MDGH), Australia, and two 
or four tablets of 2 mg will be administered, depending on the age of participants (two tablets of 2 mg 
for 6-7 year-olds and four tablets of 2 mg for 8-12 year-olds). Albendazole will be the product of GSK 
(Zentel®) and a single tablet of 400 mg will be administered. Albendazole placebo tablets will be 
purchased from Fagron, Germany. 
The tablets will be handed out from four drug containers (moxidectin, moxidectin placebo, albendazole 
and albendazole placebo). According to the randomisation list, each person will receive either: 
(i) 
Two or four tablets of moxidectin plus a single tablet of albendazole 
(ii) 
Two or four tablets of moxidectin placebo plus a single tablet of albendazole 
(iii) 
Two or four tablets of moxidectin placebo plus a single tablet of albendazole placebo 
 

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All drugs will be administered in the presence of the Principal Investigator (PI) and/or Co-PI, and 
ingestion confirmed. This will be recorded with the time and date of dosing. Participants will be asked 
to limit the use of any drugs other than those prescribed by the study medical team for the duration of 
the study as described in section 5.5. After ingestion of the medication, the participants will be observed 
for three hours to ensure retention of the drug. Vomiting within one hour post-dosing will require re-
dosing. The participants will not be allowed more than one repeated dose. No re-administration will be 
needed for participants vomiting after one hour. The PI or the Co-PIs are responsible for drug 
accountability at the study site. Maintaining drug accountability includes careful and systematic study 
drug storage, handling, dispensing, and documentation of administration. Prior to administration, drugs 
will be stored at room temperature and protected from light and exposure to moisture in a secure area 
with limited access at the study site. 
To avoid interference of potential on-going control programs against helminthiases with the infection 
status of the trial participants, communication with local stakeholders will be established to ascertain 
that trial participants will not undergo MDA treatment. Missed-out rounds of planned MDA against 
STH infections will be substituted with a free single-dose treatment (albendazole 400 mg) against STH 
infection after the follow-up assessment, offered by the study team to all community members not 
participating in the trial in communities screened. 
4.3.5 
Pharmacokinetic analysis 
The PK and exposure-response correlation study will be performed in 24 participants in the moxidectin-
albendazole arm (12 per moxidectin dose), randomly selected by location. Since PK population 
parameters of moxidectin are available, a sparse sampling approach can be applied to describe the PK 
profile [21, 31]. Within a sparse sampling approach, instead of describing the PK profile for each 
participant separately, samples are allocated to different time points and/or individuals within the same 
treatment. Statistical inferences are performed to characterize the population-based PK profile of a 
specific dose. This approach allows for a reduced number of samplings per dose and renders a PK 
characterization well tolerable. To this end, a small drop of blood from the fingertip will be taken for a 
maximum of 5 finger pricks per participant. The exact time points are 1h, 2h, 4h, 6h, and 24h, covering 
the relevant time span identified previously [21, 31]. Capillary blood (~10 µl) will be collected by 
puncture with a finger prick. Two micro-samples (duplicates) will be taken with one finger prick. Each 
time, the drop of blood (10 µl) will be directly transferred on Mitra® sticks [31]. The dried sticks will be 
transported to Swiss TPH and stored at room temperature until analysis (< 2 months post-treatment). 
The quantification of the study drugs will be performed using the validated liquid chromatography 
tandem mass spectrometry (LC-MS/MS) method as described elsewhere [31]. Drug concentrations will 
be calculated by interpolation from a calibration curve with a lower limit of quantification of 1-5 ng/ml. 
7% of the sample duplicates will be analysed for quality control, and the measured concentrations will 
be used to determine between-run and overall precision and accuracy of the analysis. 

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4.3.6 
Safety assessment 
Participants will be monitored at the site (i.e. school) for three hours after treatment administration to 
observe any possible acute AEs (continuous observation) and reassessment will be done at 24 hours 
post-treatment (follow-up visit). Additionally, interviews will be conducted to determine the emergence 
of clinical symptoms such as headache, abdominal pain, itching, nausea, vomiting and diarrhoea directly 
before treatment within the scope of baseline assessment. At three and 24 hours and 14-21 days after 
treatment participants will again be interviewed for the assessment of AEs. Symptoms arising within 
three hours after treatment and the follow-up time points will be monitored by parents/caregivers, 
teachers or local healthcare workers who will report incidences to the study team. Any symptoms will 
be recorded in the designated case report form (CRF) and immediate action will be undertaken if 
indicated. 
4.3.7 
Efficacy assessment 
The efficacy of the treatment will be determined at 14-21 days post-treatment by collecting another two 
stool samples, which will be microscopically examined for T. trichiura, A. lumbricoides and hookworm 
eggs using quadruplicate Kato-Katz thick smears (two slides per sample). Quality control will be 
performed as described for the initial diagnosis (see section 4.3.1). All microscopically analysed 
quadruplicate Kato-Katz thick smears will be destroyed after passing the quality control. 
Participants will be considered cured for an infection if no corresponding eggs are found in the follow-
up stool samples. At the end of the study, all participants remaining positive for T. trichiura or any co-
infection will be treated with the currently best recommended treatment. 
4.4 
Measure to minimise bias 
Study participants eligible for treatment will be randomly assigned to one of the three treatment arms 
using a computer-generated stratified randomisation code. The random allocation sequence with random 
block sizes of 6 and 12 and stratified by two levels of age category (6-7 years and 8-12 years) and two 
levels of baseline T. trichiura infection intensity (light: 1-999 EPG, and moderate or heavy: ≥1000 
EPG) will be provided by a statistician. Allocation concealment will be warranted using opaque, sealed 
envelopes containing the randomisation lists. All treatment arms will be double-blinded (i.e. study 
participants and trial team members assessing the outcomes will be blinded) using appearance-matching 
placebos. In the case of accidental unblinding or necessary code breaks, the sponsor will be immediately 
notified (within 24 hours) and data will be analysed as set forth in section 8.3. 
4.5 
Study duration and duration of participation 
The trial will last two months. Baseline screening is scheduled to start one month prior to treatment and 
follow-up stool sample collection will take place at 14-21 days after treatment, lasting approximately 
two weeks. Thus, the maximum time for participation will be two months. Schedules of visits are 
summarised in Table 1. 

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Table 1. Schedule of study visits. 
 
Screening 
Baseline/Treatment/Safety 
Follow up 
Day -30 to -1 
Day 0 
Day 14 to 21 
 
 
0h 
Randomisation and treatment 
1h 
2h 
3h 
4h 
6h 
24h 
Informed consent 
X 
 
 
 
 
 
 
 
 
Diagnosis (stool examination) 
X 
 
 
 
 
 
 
 
X 
Medical history 
 
X 
 
 
 
 
 
 
 
Clinical examination 
 
X 
 
 
 
 
 
 
 
Haemoglobin measurement 
 
X 
 
 
 
 
 
 
 
PK (microsampling) 
 
 
X 
X 
 
X 
X 
X 
 
Capturing AEs and SAEs 
 
 
 
 
X 
 
 
X 
X 
 
5. Selection of trial participants 
5.1 
Recruitment 
The trial will be carried out in children aged 6-12 years in the Wete district, Pemba Island, Tanzania. 
The trial will be implemented as school-based study in communities with endemicity of T. trichiura 
infection above 20% identified during previous trials. Parents/caregivers of potential participants will 
be invited to participate in an information session. The research team will explain the purpose and 
procedures of the study, as well as potential benefits and risks of participation. Attendees will be 
encouraged to ask questions which will be discussed in an open setting. 
Parents/caregivers interested in having their child participate in the study will be invited to complete the 
informed consenting process by signing the informed consent form (ICF). In addition, participants will 
be asked to sign an assent form. Participants having a signed ICF and assent form will be assessed for 
eligibility during screening procedures. 
5.2 
Inclusion criteria 
1. 
Aged between 6 and 12 years (confirmed by birth certificate or similar document). 
2. 
Written informed consent signed by parents/caregivers and assent by participant. 
3. 
Agree to comply with study procedures, including provision of two stool samples at the beginning 
(baseline) and at follow-up assessment 14-21 days after treatment. 
4. 
At least two slides of the quadruplicate Kato-Katz thick smears positive for T. trichiura. 
5. 
Willing to be examined by a study physician prior to treatment. 

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5.3 
Exclusion criteria 
1. 
Presence or signs of major systemic illness, e.g. fever (temporal body temperature ≥ 38°C) or severe 
anaemia (Hb level <80 g/l according to WHO [32]) upon initial clinical assessment. 
2. 
History of severe acute disease or unmanaged, severe chronic disease (i.e., condition is not as 
therapeutically controlled as necessary). 
3. 
Use of anthelminthic drugs during study period. 
4. 
Known allergy to study medication (i.e. moxidectin, albendazole). 
5. 
Being prescribed or taking concomitantly medication with known contraindication or drug 
interactions with the study medication. 
6. 
Pregnancy (female participants aged 10-12 years). 
7. 
Concurrent participation in other clinical trials. 
5.4 
Criteria for discontinuation of trial 
A participant can be discontinued from the study for the following reasons: 
1. 
Withdrawal from the study (this can happen anytime as participation is voluntary and there are no 
further obligations once a participant withdraws). 
2. 
At the discretion of the PI or Co-PI, if the participant is not compliant to the requirements of the 
protocol. 
Discontinued participants will not be replaced. If, for any reason, a participant is discontinued from the 
study before the end of treatment evaluations, the AE assessment will still be conducted. Data obtained 
prior to the withdrawal will be included in the analysis to ensure the validity of the trial. Data of 
withdrawn participants are fully anonymised once analysis is complete. 
5.5 
Concomitant medication 
All medications taken between one month before treatment and the follow-up assessment at 14-21 days 
post-treatment must 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 participants 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. Participants receiving active 
anthelminthic concomitant medication during the trial will not be discontinued; however, a case-specific 
assessment will be done at the point of data analysis. 
 
6. Safety assessments 

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6.1 
Adverse event definitions 
The term “adverse event” (AE) is defined as follows: 
Any untoward medical occurrence in a patient or clinical investigation participant administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment. 
An AE could therefore include any of the following events, which develop or increase in severity during 
the course of the study, after administration of the study product: 
a. Any unfavourable and unintended signs, symptoms or disease temporally associated with the use of 
a medicinal product, whether or not considered related to the condition under study and the study 
product. 
b. Any abnormality detected during physical examination. 
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 considered as baseline medical conditions. For the purpose of 
this trial, disease progression and relapse will be considered as failure of prescribed treatment or failure 
of treatment administration, not as an AE. 
The observation time for AEs starts when the treatment is initiated until the end of the study. 
These data will be recorded on the appropriate CRF sections, 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 (see also 
relatedness definitions below). 
6.1.1 
Severity grading 
Adverse signs or symptoms will be graded by the physician or nurse of the trial as mild, moderate, 
severe or life threatening according to the following definitions: 
Grade 
Definition 
1 
Mild: the participant is aware of the event or symptom, but the event or symptom is 
easily tolerated. 
2 
Moderate: the participant experiences sufficient discomfort to interfere with or 
reduce his or her usual level of activity. 
3 
Severe: significant impairment of functioning: the participant is unable to carry out 
his or her usual activities. 
4 
Life-threatening or disabling 
5 
Death related to AEs 
 

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6.1.2 
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 AE, 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”. 
6.1.3 
Expectedness 
Expected adverse drug reaction: Any AE possibly related to the administration of moxidectin, 
albendazole or moxidectin-albendazole combination reported in the literature or on the drug package 
leaflets, if available, and listed in the consent form. 
Unexpected adverse drug reaction: Any AE possibly related to the study drug administration, the nature, 
frequency, specificity or severity of which is unanticipated and not consistent with the available risk 
information described for these drugs. 
6.1.4 
Serious adverse events 
According to the ICH “Clinical Safety Data Management: Definitions and standards for expedited 
Reporting E2A” [33], a serious adverse event (SAE) includes any event (experience) or reaction in any 
untoward medical occurrence that at any dose: 
1. results in death; 
2. is life-threatening, meaning, the participant 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. results in persistent or significant disability/incapacity, i.e. the event causes a substantial 
disruption of a person’s ability to conduct normal life functions; 
4. requires inpatient hospitalization or prolongation of existing hospitalization; 
5. creates a congenital anomaly or birth defect (not relevant for this study); 
6. is an important medical event, based upon appropriate medical judgement, that may 
jeopardize the participant or may require medical or surgical intervention to prevent one 
of the other outcomes defining serious. 
 

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A “severe” AE does not necessarily meet the criteria for a “serious” AE. SAEs are reported from 
treatment until the end of the study. 
SAEs that are still ongoing at the end of the study period will be followed up to determine the final 
outcome. 
The causality of any SAE that occurs after the study period and its possible relatedness to the study 
treatment or study participation will also be assessed by investigators as described in section 6.1.2. 
6.1.5 
Suspected unexpected serious adverse reactions 
A suspected unexpected serious adverse reaction (SUSAR) is an unexpected adverse drug reaction, 
which also meets the definition of SAE. 
6.2 
Methods of recording and assessing adverse events 
Few AEs have been reported following moxidectin, albendazole, or moxidectin-albendazole co-
administration in STH infected individuals. The most common AEs were abdominal cramps, headache, 
fatigue, nausea, diarrhoea, fever, and vertigo. Such symptoms can, however, also result from the 
infection itself. Such side effects may be more frequent and/or serious in patients with a heavy worm 
burden. 
The observation time for AEs starts when the treatment is initiated. Participants will be observed for at 
least three hours following treatment for any acute AE and reassessment will be done at 24 hours and 
14-21 days post-treatment. 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 
at three and 24 hours as well as at 14-21 days after treatment about the occurrence of AEs. Any potential 
AEs happening between three hours post-treatment and the further follow-up time points (24 hours and 
14-21 days) will be monitored and managed with the help of the locally based medical team (including 
specifically trained community health workers, nurses and medical doctors). Medical intervention will 
be provided if necessary. 
Information on all AEs (incidence, intensity, seriousness and causality) will be entered immediately in 
the appropriate AE module of the CRF. 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 Medicines Agency (Note for Guidance on Clinical Safety Data Management). 
All SAEs, unexpected adverse drug reactions or SUSARs must be reported as described in Section 6.3. 

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6.3 
Reporting of serious adverse events 
Any study-related unanticipated problem posing risk of harm to participants or others (including all 
unexpected adverse drug reactions), and any type of SAE will be immediately (within a maximum of 
24 hours after becoming aware of the event) notified to the study sponsor-investigator and Co-PIs: 
Prof. Dr. Jennifer Keiser (Sponsor-Investigator/PI) 
Swiss Tropical and Public Health Institute 
Kreuzstrasse 2, 4123 Allschwil, Switzerland 
Tel.: +41 61 284 82 18 
Fax: +41 61 284 81 05 
Email: jennifer.keiser@swisstph.ch 
 
Mr. Said Mohammed Ali (Co-PI) 
Public Health Laboratory Ivo de Carneri 
P.O. Box 122 Wawi, Chake Chake, Pemba, Tanzania 
Tel.: +255 24 245 20 03 
E-mail: saidmali2003@yahoo.com 
Within the following 48 hours, the local co-investigator must provide further information on the SAE 
or the unanticipated problem in the form of a written narrative to the study sponsor-investigator. 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 SAE 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 SAE 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). 
All pregnancies in enrolled participants will be reported to the sponsor-investigator within 48 hours of 
becoming aware of the pregnancy. In the event of pregnancy in a treated participant, she should be 
monitored until the conclusion of pregnancy. The outcome of the pregnancy and any complications must 
be reported to the sponsor-investigator within 48 hours. 
6.4 
Safety reporting to Health Authorities, Ethics Committees and other third parties 
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 responsible 
ethics committee in Switzerland and Zanzibar according to national rules. Fatal or life-threatening SAEs 
or SUSARs will be reported within 24 hours followed by a complete report within 7 additional calendar 
days. Other SAEs 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. SAEs involving moxidectin will 
be reported to the manufacturer in accordance with agreements. 

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6.5 
Rescue medication strategy 
In case an adverse event requires medical intervention, this will be performed by the study physician 
and in accordance with local medical guidelines. Given the most common adverse events (headache, 
abdominal pain, itching, nausea, vomiting and diarrhoea), analgesics and antipyretics (e.g. paracetamol) 
are allowed to be given to participants in case of pain or fever, antiemetics (e.g. dimenhydrinate) to 
prevent nausea and vomiting and/or antibiotics to prevent or treat bacterial superinfection. In addition, 
electrolyte replacement solution in case of severe vomiting and diarrhoea, immunosuppressants (e.g. 
dexamethasone) in case of allergies or immune system over-reaction (e.g. due to a high amount of worms 
being expulsed) or an adsorptive antidote (e.g. activated charcoal) may be administered. 
At the end of the study, all participants remaining positive for T. trichiura or any co-infection will be 
treated with the currently best recommended treatment. 
 
7. Data management and data quality control 
The investigators are responsible for an adequate data quality. Prior to the initiation of the study, a short 
investigator’s meeting will be held between investigators of Swiss TPH and PHL-IdC. This meeting will 
include a detailed discussion of the protocol, performance of study procedures (standard operating 
procedures from previous studies available on site), CRF completion, specimen collection and 
diagnostic methods. 
7.1 
Source data 
Source data are comprised of clinical findings and observations as well as laboratory data maintained 
and compiled at the study site. Source data are contained in hardcopy source documents and are allowed 
to be accessed by local authorities. Source data will be directly entered in the following documents: 
1. CRF: Primary data collection instrument for the study. It holds records of all clinical and 
physical examination data, treatment information and AEs. For every participant enrolled in the 
clinical trial a corresponding CRF exists. All data requested on the CRF must be recorded, and 
investigators will review and approve each CRF for completion. 
2. Census: Holds name, age and sex of each potential participant. 
3. Laboratory parasitology sheets: Record of the T. trichiura, A. lumbricoides and hookworm egg 
counts at all sample collection time points. 
4. PK: Time records of PK sample collection. 
7.2 
Data collection and documentation 
Data collected and produced within this trial will fall into one of the following categories: 
a) Egg counts of T. trichiura, A. lumbricoides and hookworm derived from quadruplicate Kato-
Katz microscopy performed at baseline as well as at 14-21 days post-treatment. 

moxiped_protocol_v1.1_20240402 
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b) Anthropometric and clinical characteristics of the trial participants collected using the study’s 
CRF such as weight, height, blood pressure, temperature, pregnancy status (for female 
participants aged 10-12 years), overall health status and any abnormal medical condition or 
chronic disease. 
c) Finger prick blood samples for haemoglobin measurement and PK analysis. 
d) Collection date and time of each PK sample. 
e) Measured concentrations analysed from finger prick blood samples and subsequently derived 
PK parameters. 
All data categories will be recorded paper-based (primary data source), e.g. on the CRF, and double-
entered into the electronic data collection software REDCap (Vanderbilt University, US) using tablets. 
In this case, the paper-based data will represent the primary data source. All entries will be printed in 
blue ink and all corrections must be documented with date and initials of the respective team member. 
Double-entered data will be compared using the REDCap internal ‘Data Comparison Tool’ and any 
discrepancies will be reviewed against the hardcopies of the CRF and corrected accordingly. All data 
files in REDCap will be merged into a master file and saved as .xlsx and/or .csv file. Data analysis will 
be conducted with pseudonymised data and reporting of findings will be fully anonymised. 
7.3 
Ethical, legal and security issues 
Information about study participants will be kept confidential and managed accordingly. Screened 
participants will be listed in a confidential “participant screening log” and attributed a unique participant 
ID (PID). In case of enrolment, participants will be listed in a confidential “participant enrolment log” 
utilizing the same PID. The PID will be linked with the participant’s identity on a separate file 
(participant identification list), filed in a secured place at PHL-IdC. This document will constitute the 
only source to decode the pseudonymised data and will only be accessible to investigators. 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 participants. Confidentiality will be ensured throughout the entire 
research project. All databases will be password secured. None of the investigators declare to have any 
conflicts of interest. 
7.4 
Data storage and preservation 
All samples containing biological material will be destroyed after completion of the study. Paper-based 
and electronic source data and related material will be preserved for a minimum of 15 years to enable 
understanding of the study procedures, which allows the work to be assessed retrospectively and 
repeated if necessary. The study site (PHL-IdC) will retain the original hardcopy source documents such 
as CRFs to ensure that local collaborators can provide access to these documents to a monitor, auditor, 
or regulatory agency. Essential infrastructure such as a locked room for safe storage of hardcopy data 
will be made available. Electronic copies of source documents will be transferred to Swiss TPH, 

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Allschwil, Switzerland, for storage on secured network drives with restricted access for study personnel 
only. The primary storage of electronic data will be within REDCap on the Swiss TPH shared server 
and strictly confidential by password protection. The entire REDCap project (including all data) will be 
backed up regularly, e.g. weekly. Secondary data storage will be on personal, password-protected 
laptops of the PI and Co-PIs, and on a flash drive kept by Co-PIs at the study site. 
7.5 
Study documents: translations – reference language 
- 
The protocol master document will be in English, all further language versions (e.g. Kiswahili) 
are translated thereof. 
- 
The ICF master document will be in English, all further language versions (e.g. Kiswahili) are 
translated thereof. 
- 
The CRF master document will be in English, all further language versions (e.g. Kiswahili) 
are translated thereof. 
 
8. Statistics 
8.1 
Definition of primary endpoint 
T. trichiura infection status 14-21 days post-treatment assessed by quadruplicate Kato-Katz is the 
primary endpoint in our study. 
8.2 
Justification of number of trial participants 
The primary analysis of this trial aims to assess whether combined moxidectin and albendazole is more 
efficacious against T. trichiura infection compared to standard of care therapy (albendazole 
monotherapy) in SAC. We assumed a true CR of 30% for moxidectin-albendazole combination and 10% 
for albendazole monotherapy against T. trichiura. Assuming a loss to follow-up of 15% and requiring 
an allocation ratio of 3:2, we estimated that enrolling 105 participants in the moxidectin-albendazole 
combination arm and 70 participants in the albendazole monotherapy arm will be sufficient to identify 
a statistically significant difference with 85% power using a two-sided 5% significance level. 
Additionally, 35 individuals will be included for the placebo only arm to evaluate safety findings. In 
total, we anticipate to recruit 210 participants. 
The suggested sample size of a maximum 5 PK samples from 24 participants (12 per moxidectin dose) 
is sufficiently high to determine the population PK parameters with a sparse sampling scheme. 
8.3 
Description of statistical methods 
The primary analysis will use the full analysis set (available case population) according to the intention-
to-treat principles defined as all randomised participants who provide any follow-up data. Only 
randomised participants not providing follow-up data as well as participants who were negative at 

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baseline and erroneously randomised will be excluded from the analysis. In addition, a per-protocol 
analysis will be conducted. Eligibility for analysis sets will be determined before unblinding. CRs will 
be calculated as the percentage of egg-positive participants at baseline who become egg-negative after 
treatment. Differences between CRs will be assessed by using logistic regression with only treatment 
and stratification variables included in the model. Results will be reported overall and by relevant 
stratification variable. 
EPG will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and 
multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated 
for the different treatment arms before and after treatment to assess the corresponding ERRs (see 
formula). 
𝐸𝑅𝑅=  1 − 
1
𝑛 𝑒 ∑log(𝐸𝑃𝐺𝑓𝑜𝑙𝑙𝑜𝑤−𝑢𝑝 + 1) −1
1
𝑛 𝑒 ∑log(𝐸𝑃𝐺𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒 + 1)      −1
 
Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals 
(CIs) for ERR point estimates and the difference between the ERRs. 
Previous similar trials have shown that the proportion of participants lost to follow-up is usually far 
below 10%, therefore, no imputation of missing data will be performed. Infection status and egg counts 
of participants with incomplete data at follow-up (i.e. only one stool sample available at follow-up) will 
be estimated based on the available data. This means a participant is considered infected if any sample 
is positive and EPGs will be calculated as mean egg count of the available sample multiplied by 12. 
The safety analysis set will include all treated participants. AEs will be evaluated descriptively focusing 
on the proportion of participants reporting symptoms before and after treatment in each arm. 
Previously established nonlinear mixed-effects (NLME) models will be used to compare and determine 
PK parameters [21, 31]. Concentrations are measured with a validated LC-MS/MS method [31]. Using 
NLME, the following key PK parameters will be calculated: 
 
Cmax 
maximal plasma concentration 
 
tmax 
time to reach Cmax 
 
AUC area under the curve, from 0 to 24 h and 0 to inf. 
 
t1/2 
elimination half-life 
Cmax and tmax will be observed values derived from the plasma concentration-time profile. Total drug 
exposure (AUC) and t1/2 will be calculated with the WinNonlin software package using compartmental 
analysis. The elimination half-life will be estimated by the equation: t1/2 = ln2/, where  (the elimination 
rate constant) will be determined by performing a regression of the natural logarithm of the 

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concentration values during the elimination period. Primary PK parameters including absorption rate 
(ka), volume of distribution (V), and clearance (CL) will be estimated utilizing NLME modelling. In 
addition, exploratory pharmacometric PK and exposure-response analyses may be performed with the 
Monolix or NONMEM software package. 
 
9. Duties of the investigator 
9.1 
Investigator’s confirmation 
This trial will be conducted in accordance with the protocol, International Conference on Harmonisation 
Good Clinical Practice E6 (R2) (ICH-GCP) and the current version of the Helsinki Declaration.[34, 35] 
All protocol modifications must be documented in writing. A protocol amendment can be initiated by 
either the Sponsor-Investigator/PI or any Co-PI. The Investigator will provide the reasons for the 
proposed amendment in writing and will discuss with the Sponsor-Investigator/PI and Co-PIs. Any 
protocol amendment must be approved and signed by the Sponsor-Investigator/PI and must be submitted 
to the appropriate Independent Ethics Committee (IEC) for information 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 
participants, or when the change involves only logistical or administrative aspects of the trial, e.g. 
change of telephone number(s). 
9.2 
Damage coverage 
A general liability insurance of the Swiss TPH is in place (Winterthur Insurance, Policy No. 4746321) 
and a participant liability insurance has been issued in Pemba, Tanzania (National Insurance 
Cooperation of Tanzania LTD, Policy No. IMIS/GL/P/25/1/2024/771417). 
9.3 
Project management 
The trial team will include the PI (Prof. Jennifer Keiser), three Co-PIs (Said Mohammed Ali, Viviane 
Sprecher, Annina Schnoz), a study physician (Dr. Ibrahim Said Mohammed), a study pharmacist 
(Viviane Sprecher), and a statistician (Dr. Jan Hattendorf), as well as a local medical team and several 
laboratory technicians. The PI and Co-PIs 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. The Co-PIs are responsible for supervision of the 
lab and field technicians, staff management, participant recruitment and enrolment monitoring, supply 
of the material, contact to the local authorities and participating communities. 
The study site (PHL-IdC) has more than 20 years of research experience with a special focus on 
neglected tropical diseases, including trichuriasis, and owns well-established diagnostic laboratories in 
parasitology and other infectious disease fields, run by trained and experienced technicians. 

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Infrastructure as required for the study needs will be installed as necessary before study launch. The 
investigator team is responsible for ensuring that the protocol is strictly followed. No changes should be 
made without the agreement of the PI and the Co-PIs, except when necessary to eliminate an apparent 
immediate hazard or danger to a study participant. All investigators will work according to the protocol 
and GCP. All investigators 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 Co-PI. All entries have to be made clearly readable with a 
pen. All investigators must be thoroughly familiar with the properties, effects and safety of the 
investigational pharmaceutical product. 
 
10. Ethical considerations 
10.1 
Independent Ethics Committee (IEC) 
The study will be submitted for approval by the institutional research commission of Swiss TPH and the 
ethical committees of Switzerland and Zanzibar. The study will be undertaken in accordance with the 
Declaration of Helsinki and ICH-GCP. 
10.2 
Evaluation of the risk-benefit ratio 
Moxidectin and albendazole are well-known drugs and have little and mainly mild AEs as described to 
date (headache, abdominal pain etc.). Moxidectin is an FDA-approved drug against onchocerciasis and 
has been tested for trichuriasis in adolescents and adults. In the phase 1 study conducted in children and 
adolescents aged 4-17 years moxidectin was well tolerated in all age cohorts in the study, with no 
treatment-limiting adverse events identified during 24 weeks of follow-up and no adverse events leading 
to early study withdrawal. No adverse events were classified as serious, and no deaths were reported. 
Albendazole is a widely used drug in mass treatment programs against STH. All SAC enrolled in the 
study will benefit from a clinical examination and a treatment against STH infections. All participants 
remaining positive for T. trichiura or any co-infection will be treated with the currently best 
recommended treatment. 
10.3 
Participant information and consent 
All parents or caregivers of eligible participants will be asked to sign a written informed consent form. 
In case the parent/caregiver is illiterate, an impartial witness that can read and write has to sign the 
consent and the illiterate person has to give a thumb print. Parents or caregivers will have sufficient time 
for reflection of their child’s participation. In addition, participants will be asked to sign an assent form. 
Information sessions in the respective communities will be conducted to explain to parents/caregivers 
and potential participants the purpose and procedures of the study. Informed consent forms and assent 
forms are orally explained in local language of the parents/caregivers and participants if necessary to 
ensure comprehension. Participation is voluntary and individuals have the right to withdraw from the 

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study at any given point in time with no further obligations. Participation itself will not be awarded with 
compensation. 
10.4 
Participants requiring particular protection 
Our study will include SAC, since this population group is at high risk of T. trichiura infection. 
Superiority studies between moxidectin-albendazole combination and albendazole monotherapy have 
not been conducted to date in this population. Our trial will produce more evidence to support the search 
for a safe and effective treatment of trichuriasis in children and the whole community. 
Throughout the entire study, from the preparation phase to the dissemination of results, community 
representatives (e.g. teachers) will be consulted to ensure any concerns regarding the study can be 
tackled in an anonymous and timely manner and the study addresses the community’s needs as far as 
possible. 
 
11. Quality control and quality assurance 
11.1 
Monitoring and auditing 
We will work with a locally based external monitor. The monitor will conduct site visits to the 
investigational facilities with the purpose of monitoring the study. Details will be described in a separate 
monitoring plan. The investigators will grant access to study documentation, laboratory facilities, 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 
preventive 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. The investigators agree to allow inspectors from regulatory 
agencies to review records and assist the inspectors in their duties, if requested. 
11.2 
Data and safety monitoring board (WHO) / data monitoring committee (EU/FDA) 
In our study, we work with well-known drugs in a small sample size and using a single dose treatment. 
Nevertheless, the project advisors, Dr Said Abdallah Jongo, physician and senior clinical research 
scientist at the Ifakara Health Institute (IHI) in Bagamoyo, Tanzania, and Prof Dr Piero Olliaro, 
infectious disease physician and professor of infectious diseases associated with poverty at Oxford 
University, United Kingdom, will serve as independent data and safety monitoring board, they will be 
informed regularly and the findings discussed. This means they have the responsibility to convene, 
evaluate the study data and give their advice regarding the continuation or stopping of the study before 
the treatment, at the end of the study and in case of an important safety event. 
 
 

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12. Funding 
Funding for this trial is provided by the Swiss National Science Foundation (SNSF). This funding source 
had no role in the design of this study and will not have any role during its execution, analyses, 
interpretation of the data, or decision to submit results for publication. 
 
13. Dissemination of results and publication 
The final results of this study will be published in a peer-reviewed scientific journal and presented at 
scientific conferences. SNSF will be acknowledged as study funder. All results from this investigation 
are considered confidential and shall not be made available to any third party by any member of the 
investigating team before publication. A summary of study findings may be shared with local health 
authorities prior to publication. After publication, study results will be made available to study 
participants.

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14. References 
1. 
Pullan, R.L., et al., Global numbers of infection and disease burden of soil transmitted helminth 
infections in 2010. Parasit Vectors, 2014. 7: p. 37. 
2. 
World Health Organization. Fact sheet: Soil-transmitted helminth infections. 2023  21 August 
2023]; Available from: https://www.who.int/news-room/fact-sheets/detail/soil-transmitted-
helminth-infections. 
3. 
US Centers for Disease Control and Prevention. DPDx - Laboratory Identification of Parasites 
of Public Health Concern. US Centers for Disease Control and Prevention (CDC). 2021  [cited 
2021 31 January]; Available from: https://www.cdc.gov/dpdx/index.html. 
4. 
Jourdan, P.M., et al., Soil-transmitted helminth infections. The Lancet, 2018. 391(10117): p. 
252-265. 
5. 
World Health Organization, Ending the neglect to attain the Sustainable Development Goals: a 
road map for neglected tropical diseases 2021–2030. 2020, World Health Organization: 
Geneva. 
6. 
World Health Organization, Prevention and control of schistosomiasis and soil-transmitted 
helminthiasis: report of a WHO expert committee, in WHO Technical Report Series. 2002, 
World Health Organization: Geneva. 
7. 
World Health Organization, 2030 targets for soil-transmitted helminthiases control 
programmes. 2019, World Health Organization: Geneva. 
8. 
World Health Organization, Preventive chemotherapy in human helminthiasis - Coordinated 
use of anthelminthic drugs in control interventions: a manual for health professionals and 
programme managers. 2006, World Health Organization: Geneva. 
9. 
World Health Organization, Guideline: preventive chemotherapy to control soil-transmitted 
helminth infections in at-risk population groups. Geneva, Switzerland. 2017, World Health 
Organization: Geneva. 
10. 
World Health Organization, Model List of Essential Medicines, 22nd List. 2021, World Health 
Organization: Geneva. 
11. 
Moser, W., C. Schindler, and J. Keiser, Efficacy of recommended drugs against soil transmitted 
helminths: systematic review and network meta-analysis. BMJ, 2017. 358: p. j4307. 
12. 
Farrell, S.H., et al., Investigating the Effectiveness of Current and Modified World Health 
Organization Guidelines for the Control of Soil-Transmitted Helminth Infections. Clin Infect 
Dis, 2018. 66(suppl_4): p. S253-S259. 
13. 
Clarke, N.E., et al., Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-
transmitted Helminths: A Systematic Review and Network Meta-analysis. Clin Infect Dis, 2019. 
68(1): p. 96-105. 
14. 
Moser, W., C. Schindler, and J. Keiser, Drug Combinations Against Soil-Transmitted Helminth 
Infections. Adv Parasitol, 2019. 103: p. 91-115. 
15. 
Hughes, D. and D.I. Andersson, Evolutionary consequences of drug resistance: shared 
principles across diverse targets and organisms. Nat Rev Genet, 2015. 16(8): p. 459-71. 
16. 
World Health Organization, The Selection and Use of Essential Medicines - Report of the WHO 
Expert Committee, 2017 (including the 20th WHO Model List of Essential Medicines and the 
6th Model List of Essential Medicines for Children), in WHO technical report series. 2017, 
World Health Organization: Geneva. 
17. 
Opoku, N.O., et al., Single dose moxidectin versus ivermectin for Onchocerca volvulus infection 
in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, 
double-blind phase 3 trial. The Lancet, 2018. 392(10154): p. 1207-1216. 
18. 
Keller, L., et al., Efficacy and Safety of Ascending Dosages of Moxidectin and Moxidectin-
albendazole Against Trichuris trichiura in Adolescents: A Randomized Controlled Trial. Clin 
Infect Dis, 2020. 70(6): p. 1193-1201. 
19. 
Welsche, S., et al., Efficacy and safety of moxidectin and albendazole compared with ivermectin 
and albendazole coadministration in adolescents infected with Trichuris trichiura in Tanzania: 
an open-label, non-inferiority, randomised, controlled, phase 2/3 trial. Lancet Infect Dis, 2023. 
23(3): p. 331-340. 

moxiped_protocol_v1.1_20240402 
Page 35 of 35 
 
20. 
Sprecher, V.P., et al., Efficacy and Safety of Moxidectin-Albendazole and Ivermectin-
Albendazole Combination Therapy Compared to Albendazole Monotherapy in Adolescents and 
Adults Infected with Trichuris trichiura: A Randomized, Controlled Superiority Trial. Clin 
Infect Dis, 2023. 77(9): p. 1294-1302. 
21. 
Opoku, N.O., et al., Safety and pharmacokinetics of a single oral dose of moxidectin in subjects 
aged 4 to 17 years with (or at risk of) onchocerciasis, to identify an optimal dose for treatment 
of children 4 to 11 years: Results of an open label study. ASTMH 2022 Annual Meeting 
Abstract Book, 2022: p. 12. 
22. 
Geary, T.G., et al., Unresolved issues in anthelmintic pharmacology for helminthiases of 
humans. Int J Parasitol, 2010. 40(1): p. 1-13. 
23. 
Oshikoya, K.A., H.M. Sammons, and I. Choonara, A systematic review of pharmacokinetics 
studies in children with protein-energy malnutrition. European Journal of Clinical 
Pharmacology, 2010. 66(10): p. 1025-1035. 
24. 
Katz, N., A. Chaves, and J. Pellegrino, A simple device for quantitative stool thick-smear 
technique in schistosomiasis mansoni. Rev Inst Med Trop São Paulo, 1972. 14(6): p. 397-400. 
25. 
Dacombe, R.J., et al., Time delays between patient and laboratory selectively affect accuracy of 
helminth diagnosis. Trans R Soc Trop Med Hyg, 2007. 101(2): p. 140-5. 
26. 
Nikolay, B., S.J. Brooker, and R.L. Pullan, Sensitivity of diagnostic tests for human soil-
transmitted helminth infections: a meta-analysis in the absence of a true gold standard. Int J 
Parasitol, 2014. 44(11): p. 765-74. 
27. 
Martin, L.K. and P.C. Beaver, Evaluation of Kato Thick-Smear Technique for Quantitative 
Diagnosis of Helminth Infections *. The American Journal of Tropical Medicine and Hygiene, 
1968. 17(3): p. 382-391. 
28. 
Bergquist, R., M.V. Johansen, and J. Utzinger, Diagnostic dilemmas in helminthology: what 
tools to use and when? Trends Parasitol, 2009. 25(4): p. 151-6. 
29. 
Presland, S.L., E.R. Morgan, and G.C. Coles, Counting nematode eggs in equine faecal samples. 
Vet Rec, 2005. 156(7): p. 208-10. 
30. 
Cooke, I.R., et al., Analysis of menisci formed on cones for single field of view parasite egg 
microscopy. J Microsc, 2015. 257(2): p. 133-41. 
31. 
Hofmann, D., S. Sayasone, and J. Keiser, Development and validation of an LC-MS/MS method 
for the quantification of the anthelmintic drug moxidectin in a volumetric absorptive 
microsample, blood, and plasma: Application to a pharmacokinetic study of adults infected with 
Strongyloides stercoralis in Laos. J Chromatogr B Analyt Technol Biomed Life Sci, 2021. 1166: 
p. 122556. 
32. 
World Health Organization, Haemoglobin concentrations for the diagnosis of anaemia and 
assessment of severity (WHO/NMH/NHD/MNM/11.1). 2011, Vitamin and Mineral Nutrition 
Information System: Geneva. 
33. 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use: ICH Harmonised Tripartite Guideline. Clinical Safety Data 
Management: definition and standards for expedited reporting E2A. 1994. 
34. 
International Council for Harmonization (ICH), Integrated addendum to ICH E6(R1): Guideline 
for good clinical practice E6(R2). 2016, International council for harmonisation of technical 
requirements for pharmaceuticals for human use (ICH): Geneva, Switzerland. 
35. 
World Medical Association (WMA), WMA Declaration of Helsinki – Ethical principles for 
medical research involving human subjects. 2013, World Medical Association: Fortaleza, 
Brazil.