An Open Label Cryptosporidium Controlled Human Infection Model (CHIM) to Assess the Efficacy and Safety of ABO809 in Healthy Participants
Phase: PHASE1
Conditions: Cryptosporidium Infection, Cryptosporidiosis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development
ABO809
Clinical Trial Protocol CABO809A02101
An Open Label Cryptosporidium Controlled Human 
Infection Model (CHIM) to assess the efficacy and safety of 
ABO809 in healthy participants
Document type:
Amended Protocol Version
EUDRACT number:
N/A
Version number:
v02 (Clean)
Clinical Trial Phase:
I
Release date:
02-Dec-2021
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Trial Protocol Template Version 3.0 dated 31-Jan-2020

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Table of contents
Table of contents..................................................................................................................2
List of tables.........................................................................................................................5
List of figures.......................................................................................................................5
List of abbreviations ............................................................................................................6
Glossary of terms.................................................................................................................8
Protocol summary..............................................................................................................14
1
Introduction........................................................................................................................16
1.1
Background............................................................................................................16
1.2
Purpose...................................................................................................................17
2
Objectives and endpoints...................................................................................................18
3
Study design.......................................................................................................................19
3.1
Screening/Baseline Period .....................................................................................21
3.2
ABO809 administration and inpatient monitoring period .....................................21
3.3
Follow-up period and End of Study.......................................................................21
4
Rationale ............................................................................................................................22
4.1
Rationale for study design......................................................................................22
4.2
Rationale for dose/regimen and duration of treatment...........................................24
4.3
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs.......................................................................................................................25
4.4
Purpose and timing of interim analyses/design adaptations ..................................25
4.5
Risks and benefits ..................................................................................................26
4.5.1
Blood sample volume............................................................................28
4.6
Rationale for Public Health Emergency mitigation procedures.............................29
5
Study Population................................................................................................................29
5.1
Inclusion criteria ....................................................................................................29
5.2
Exclusion criteria ...................................................................................................30
6
Treatment...........................................................................................................................33
6.1
Study treatment ......................................................................................................33
6.1.1
Investigational and control drugs ..........................................................33
6.1.2
Additional study treatments...................................................................33
6.1.3
Supply of study treatment......................................................................33
6.2
Other treatment(s) ..................................................................................................33
6.2.1
Concomitant therapy .............................................................................33
6.2.2
Prohibited medication............................................................................34
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6.2.3
Rescue medication.................................................................................34
6.2.4
Restriction for study participants...........................................................35
6.3
Participant numbering, treatment assignment, randomization...............................37
6.3.1
Participant numbering ...........................................................................37
6.4
Treatment blinding.................................................................................................38
6.5
Dose escalation and dose modification..................................................................38
6.5.1
Dose escalation guidelines ....................................................................38
6.6
Additional treatment guidance...............................................................................39
6.6.1
Treatment compliance ...........................................................................39
6.6.2
Recommended treatment of adverse events ..........................................40
6.7
Preparation and dispensation .................................................................................40
6.7.1
Handling of study treatment and additional treatment ..........................40
6.7.2
Instruction for prescribing and taking study treatment..........................40
7
Informed consent procedures.............................................................................................41
8
Visit schedule and assessments..........................................................................................43
8.1
Screening................................................................................................................51
8.1.1
Eligibility screening...............................................................................51
8.1.2
Information to be collected on screening failures .................................51
8.2
Participant demographics/other baseline characteristics........................................52
8.3
Efficacy..................................................................................................................52
8.3.1
Cryptosporidium Antigen by EIA .........................................................52
8.3.2
Evaluation of Clinical Signs and Symptoms.........................................52
8.3.3
Appropriateness of efficacy assessments ..............................................54
8.4
Safety .....................................................................................................................54
8.4.1
Laboratory evaluations..........................................................................55
8.4.2
Electrocardiogram (ECG)......................................................................57
8.4.3
Pregnancy ..............................................................................................58
8.4.4
Appropriateness of safety measurements ..............................................58
8.5
Additional assessments ..........................................................................................58
9
Study discontinuation and completion...............................................................................60
9.1
Discontinuation and completion ............................................................................60
9.1.1
Study treatment discontinuation and study discontinuation..................60
9.1.2
Withdrawal of informed consent...........................................................61
9.1.3
Lost to follow-up...................................................................................62
9.1.4
Study stopping rules ..............................................................................62
9.1.5
Early study termination by the sponsor.................................................63
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9.2
Study completion and post-study treatment...........................................................63
10 Safety monitoring and reporting........................................................................................64
10.1
Definition of adverse events and reporting requirements......................................64
10.1.1
Adverse events.......................................................................................64
10.1.2
Serious adverse events...........................................................................66
10.1.3
SAE reporting........................................................................................67
10.1.4
Pregnancy reporting...............................................................................68
10.1.5
Reporting of study treatment errors including misuse/abuse ................69
10.2
Additional Safety Monitoring................................................................................69
11 Data Collection and Database management ......................................................................69
11.1
Data collection .......................................................................................................69
11.2
Database management and quality control ............................................................70
11.3
Site monitoring.......................................................................................................70
12 Data analysis and statistical methods.................................................................................71
12.1
Analysis sets...........................................................................................................71
12.2
Participant demographics and other baseline characteristics.................................71
12.3
Treatments..............................................................................................................72
12.4
Analysis of the primary endpoint(s)/estimand(s)...................................................72
12.4.1
Statistical model, hypothesis, and method of analysis ..........................72
12.4.2
Supplementary analysis.........................................................................72
12.5
Analysis of secondary endpoints/estimands ..........................................................72
12.5.1
Efficacy and/or Pharmacodynamic endpoint(s) ....................................72
12.5.2
Safety endpoints ....................................................................................73
12.6
Analysis of exploratory endpoints .........................................................................74
12.7
Interim analyses .....................................................................................................74
12.8
Sample size calculation..........................................................................................75
12.8.1
Primary endpoint(s)...............................................................................75
12.8.2
Secondary endpoint(s)...........................................................................75
13 Ethical considerations and administrative procedures.......................................................75
13.1
Regulatory and ethical compliance........................................................................75
13.2
Responsibilities of the investigator and IRB/IEC..................................................75
13.3
Publication of study protocol and results...............................................................76
13.4
Quality Control and Quality Assurance.................................................................76
14 Protocol adherence.............................................................................................................76
14.1
Protocol amendments.............................................................................................76
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15 References..........................................................................................................................78
16 Appendices.........................................................................................................................81
16.1
Appendix 1: Stool Grading System .......................................................................81
List of tables
Table 2-1
Objectives and related endpoints...........................................................18
Table 4-1
CHIM studies with C. parvum...............................................................25
Table 6-1
Investigational drug...............................................................................33
Table 6-2
Additional Study Treatment ..................................................................33
Table 6-3
Provisional dose levels ..........................................................................39
Table 6-4
Dose and treatment schedule.................................................................40
Table 8-1
Assessment Schedule.............................................................................44
Table 8-2
Assessments and Specifications ............................................................54
Table 8-3
Laboratory Assessments........................................................................56
Table 10-1
Guidance for capturing the nitazoxanide errors including 
misuse/abuse..........................................................................................69
Table 16-1
Stool Grading System............................................................................81
List of figures
Figure 3-1
Study Design .........................................................................................21

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List of abbreviations
AE
Adverse Event
AESI
Adverse Events of Special Interest
AIDS
Acquired Immune Deficiency Syndrome
ALT
Alanine Aminotransferase
aPTT
Activated Partial Thromboplastin Time
AST
Aspartate Aminotransferase
BMI
Body Mass Index
bpm
Beats Per Minute
BUN
Blood Urea Nitrogen
CDC
Centers for Disease Control and Prevention
CE 
C. parvum oocysts
Center No.
Center Number
CFR
U.S. Code of Federal Regulations
CHIM
Controlled Human Infection Model
CLIA
Clinical Laboratory Improvement Amendments
CMO&PS 
Chief Medical Office and Patient Safety
CRA
Clinical Research Associate
CRF
Case Report/Record Form (paper or electronic)
CRO
Contract Research Organization
CSR
Clinical Study Report
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
eCRF
Electronic Case Record/Report Form
EDC
Electronic Data Capture
EIA
Enzyme immunoassay (detects Cryptosporidium specific antigens in stool samples)
EMA
European Medicines Agency
EOS
End of Study
eSource
Electronic Source
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-Glutamyl Transferase
GMP
Good Manufacturing Practice
HBsAg
Hepatitis B Surface Antigen
HBV
Hepatitis B Virus
HCP
Healthcare Provider
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
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ICH
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use
ID50
Median Infectious Dose
IEC
Independent Ethics Committee
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IN
Investigator Notification
IND
Investigational New Drug
INR
International Normalized Ratio
IRB
Institutional Review Board
IUD
Intrauterine Device
IUS
Intrauterine System
LDH
Lactate Dehydrogenase
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram(s)
mL
Milliliter(s)
n
Number
OTC
Over The Counter
PD
Pharmacodynamic(s)
PK
Pharmacokinetic(s)
PRO
Patient Reported Outcomes
PT
Prothrombin Time
QMS 
Quality Management System
QTcF
QT interval corrected by Fridericia’s formula
RBC
Red Blood Cell(s)
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SGOT
Serum Glutamic Oxaloacetic Transaminase
SGPT
Serum Glutamic Pyruvic Transaminase
SI
International System of Units
SUSAR
Suspected Unexpected Serious Adverse Reaction
THC
Tetrahydrocannabinol
ULN
Upper Limit of Normal
ULQ
Upper Limit of Quantification
USPI
US-Package Insert
WBC
White Blood Cell(s)
WHO
World Health Organization 
WoC
Withdrawal of Consent
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Glossary of terms
Additional treatment
Medicinal products that may be used during the clinical trial as 
described in the protocol, but not as an investigational medicinal 
product (e.g. any background therapy)
Assessment
A procedure used to generate data required by the study
Biologic Samples
A biological specimen including, for example, blood (plasma, serum), 
saliva, tissue, urine, stool, etc. taken from a study participant 
Coded Data
Personal Data which has been de-identified by the investigative center 
team by replacing personal identifiers with a code.
Cohort
A group of individuals who share a common exposure, experience, or 
characteristic, or a group of individuals followed up or traced over time.
Discontinuation from 
study
Point/time when the participant permanently stops receiving the study 
treatment and further protocol required assessments or follow-up, for 
any reason. No specific request is made to stop the use of their 
samples or data.
Discontinuation from 
study treatment
Point/time when the participant permanently stops receiving the study 
treatment for any reason (prior to the planned completion of study drug 
administration, if any). Participant agrees to the other protocol required 
assessments including follow-up. No specific request is made to stop 
the use of their samples or data.
Dosage
Dose of the study treatment given to the participant in a time unit (e.g. 
100 mg once a day, 75 mg twice a day)
Electronic Data Capture 
(EDC)
Electronic data capture (EDC) is the electronic acquisition of clinical 
study data using data collection systems, such as Web-based 
applications, interactive voice response systems and clinical laboratory 
interfaces. EDC includes the use of Electronic Case Report Forms 
(eCRFs) which are used to capture data transcribed from source 
data/documents used at the point of care
End of the clinical trial
The end of the clinical trial is defined as the last visit of the last 
participant or at a later point in time as defined by the protocol 
Enrollment
Point/time of participant entry into the study at which informed consent 
must be obtained. The action of enrolling one or more participants.
eSource (DDE)
eSource Direct Data Entry (DDE) refers to the capture of clinical study 
data electronically, at the point of care. eSource Platform/Applications 
combines source documents and case report forms (eCRFs) into one 
application, allowing for the real time collection of clinical trial 
information to sponsors and other oversight authorities, as appropriate
Healthy volunteer
A person with no known significant health problems who volunteers to 
be a study participant 
Investigational drug/ 
treatment
The drug whose properties are being tested in the study
Medication number
A unique identifier on the label of medication kits
Other treatment
Treatment that may be needed/allowed during the conduct of the study 
(i.e. concomitant or rescue therapy)
Participant
A trial participant (can be a healthy volunteer or a patient). “Participant” 
terminology is used in the protocol whereas “Subject” is used in data 
collection

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Participant number
A unique number assigned to each participant upon signing the 
informed consent. This number is the definitive, unique identifier for the 
participant and should be used to identify the participant throughout the 
study for all data collected, sample labels, etc.
Patient-Reported 
Outcome (PRO)
A measurement based on a report that comes directly from the patient 
about the status of a participant's health condition without amendment 
or interpretation of the patient's report by a clinician or anyone else
Period
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-
up) which are described in the Protocol. Periods define the study 
phases and will be used in clinical trial database setup and eventually in 
analysis
Personal data
Participant information collected by the Investigator that is coded and 
transferred to Novartis for the purpose of the clinical trial. This data 
includes participant identifier information, study information and 
biological samples.
Randomization
The process of assigning trial participants to investigational drug or 
control/comparator drug using an element of chance to determine the 
assignments in order to reduce bias.
Re-screening
If a participant fails the initial screening and is considered as a Screen 
Failure, he/she can be invited once for a new Screening visit after 
medical judgment and as specified by the protocol
Remote
Describes any trial activities performed at a location that is not the 
investigative site where the investigator will conduct the trial, but is for 
example a home or another appropriate location
Screen Failure
A participant who did not meet one or more criteria that were required 
for participation in the study
Source Data/Document
Source data refers to the initial record, document, or primary location 
from where data comes. The data source can be a database, a dataset, 
a spreadsheet or even hard-coded data, such as paper or eSource
Start of the clinical trial
The start of the clinical trial is defined as the signature of the informed 
consent by the first participant
Study treatment
Any drug or combination of drugs   or intervention administered to the 
study participants as part of the required study procedures; includes 
investigational drug(s), control(s) or background therapy
Study treatment 
discontinuation
When the participant permanently stops taking any of the study drug(s) 
prior to the defined study treatment completion date (if any) for any 
reason; may or may not also be the point/time of study discontinuation 
Tele-visit
Procedures or communications conducted using technology such as 
telephone or videoconference, whereby the participant is not at the 
investigative site where the investigator will conduct the trial.
Treatment arm/group 
A treatment arm/group defines the dose and regimen or the 
combination, and may consist of 1 or more cohorts.
Variable (or endpoint)
The variable (or endpoint) to be obtained for each participant that is 
required to address the clinical question. The specification of the 
variable might include whether the participant experiences an 
intercurrent event.

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Withdrawal of study 
consent (WoC) / 
Opposition to use of data 
/biological samples
Withdrawal of consent from the study occurs when the participant 
explicitly requests to stop use of their data and biological samples 
(opposition to use data and biological samples) AND no longer wishes 
to receive study treatment, AND does not agree to further protocol 
required assessments. This request should be in writing (depending on 
local regulations) and recorded in the source documentation.
Opposition to use data/biological samples occurs in the countries where 
collection and processing of personal data is justified by a different legal 
reason than consent.

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IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation.

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Protocol summary
Protocol 
number
CABO809A02101 
Full Title
An Open Label Cryptosporidium Controlled Human Infection Model (CHIM) to 
assess the efficacy and safety of ABO809 in healthy participants.
Brief title
Study of efficacy and safety of ABO809 in healthy participants.
Sponsor and 
Clinical Phase
Novartis
Phase I study
Investigation 
type
Biological
Study type
Interventional
Purpose and 
rationale
The goal of this Phase I CHIM study is to determine if oral administration of a 
GMP supply of Cryptosporidium parvum oocysts (ABO809) to healthy volunteers 
results in Cryptosporidium infection and diarrheal illness. The study will measure 
fecal Cryptosporidium oocysts (parasitological endpoint) as well as diarrhea and 
associated signs and symptoms (clinical endpoint). A similar CHIM model would 
be used in future studies to evaluate the efficacy of novel therapies and vaccines 
for the treatment and prevention of Cryptosporidium infection in healthy 
participants before they are assessed in the pediatric target population.
Primary 
Objective(s)
The primary objective of this study is to evaluate the incidence of 
Cryptosporidium infection following an oral administration of ABO809.
Secondary 
Objectives
The secondary objectives of this study are to evaluate the incidence and 
characteristics of diarrheal illness following an oral administration of ABO809, to 
evaluate the time to onset and resolution of Cryptosporidium infection in 
participants who developed an infection following administration of an oral 
ABO809 administration, and to assess the safety and tolerability of ABO809.
Study design
The study will consist of up to a 28-day Screening/Baseline period, after which a 
single dose of ABO809 will be administered to all participants. This will be 
followed by a 10-day inpatient monitoring period, an outpatient follow-up period, 
and a study completion visit on Day 56. Following the Day 56 visit, there will be a 
Post-Study Follow-Up call conducted at 6 months and 12 months. Participants 
who develop a Cryptosporidium infection, with or without clinical symptoms, will 
receive a standard 3-day course of nitazoxanide treatment per the U.S. 
Prescribing Information on Day 21. A total of up to 6 sequential cohorts of 
approximately 10 participants each will be enrolled.
Study 
population
Up to approximately 60 healthy male and female participants between 18 to 50 
years of age without a history of Cryptosporidium infection will be enrolled in this 
study.
Key Inclusion 
criteria
Key inclusion criteria include demonstrated understanding of Cryptosporidium 
disease, safety measures and transmission risks, good health, and ability to 
communicate well with the Investigator.
Key Exclusion 
criteria
Key exclusion criteria are history of Cryptosporidium infection, gastrointestinal 
conditions (including diarrheal syndromes, gastroenteritis and gastrointestinal 
tract surgery), immunodeficiency, infections, significant medical concerns, 
hypersensitivity to nitazoxanide or other specified antibiotics.

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ABO809 
administration
GMP Cryptosporidium parvum oocysts (ABO809) administered orally.
Treatment of 
interest
There is no "Treatment of interest" per se since this study aims to establish a 
human controlled infection model for cryptosporidiosis. In this protocol, we 
consider ABO809 as the “Intervention of interest” instead. 
Efficacy 
assessments
The primary endpoint is the number of participants with Cryptosporidium infection 
(presence of fecal oocysts) ≥72 hours following administration of an oral 
administration of ABO809 (or sooner if associated with symptoms suggestive of 
diarrheal illness). Secondary endpoints include characterization of diarrheal 
illness, safety and tolerability.
Key safety 
assessments
Safety assessments will include vital signs, ECG, safety laboratory assessments, 
AEs and SAEs.
Other 
assessments
Data analysis
The number and proportion (in percentage) of participants 
with Cryptosporidium infection will be summarized. The 1-sided 80% exact 
confidence interval with a lower limit of the proportions will also be reported. In 
addition, the number and proportion of participants with diarrheal illness will be 
reported in the same fashion.
Key words
Controlled Human Infection Model, CHIM, infection, diarrhea, safety, tolerability, 
healthy volunteers, Phase I, cryptosporidiosis, Cryptosporidium, oral, ABO809
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1
Introduction
1.1
Background
Recent studies have found Cryptosporidium infections to be a leading cause of pediatric 
diarrhea worldwide (Kotloff et al 2013, Platts-Mills et al 2015). In certain vulnerable 
populations, the infection is protracted and potentially life threatening, including young children 
(i.e., aged 0-2), malnourished children of any age, and immunocompromised individuals (e.g., 
those with HIV/AIDS). Furthermore, repeated Cryptosporidium infections in children are 
associated with long-term and debilitating growth-stunting as well as impairment in cognitive 
development (Guerrant et al 2013, Checkley et al 1998, Platts-Mills et al 2015). In children, 
even asymptomatic infections are associated with growth deficits (Checkley et al 1997). In 
addition, cryptosporidiosis remains a common cause of chronic diarrhea in HIV/AIDS patients 
in developing countries (Panel on Opportunistic Infections 2018).
Cryptosporidium species (spp.) are protozoan parasites responsible for enteritis with watery 
diarrhea as the primary clinical symptom. Cryptosporidiosis in humans is caused primarily by 
two species, Cryptosporidium hominis and Cryptosporidium parvum (Checkley et al 2015). 
Transmission typically occurs when feces containing Cryptosporidium oocysts from infected 
animals/humans contaminate food and water supplies, thereby infecting humans via the fecal-
oral route. Once ingested, the oocysts reach the small intestine where motile, infectious 
sporozoites are released from the oocysts and infect intestinal epithelial cells. The organism 
typically then goes through multiple cycles of asexual followed by sexual reproduction, 
ultimately resulting in excretion of numerous mature oocysts in the feces. Individuals may shed 
108-109 oocysts during an infection period and may excrete oocysts for up to 50 days after 
resolution of diarrhea (Putignani and Menichella 2010).
Cryptosporidiosis typically is a self-limiting infection in immunocompetent adults. Following 
infection, healthy, immunocompetent individuals may experience profuse, watery, non-bloody 
diarrhea after an incubation period of 3-12 days (Chappell et al 1999). Acute watery diarrhea 
as the cardinal symptom of cryptosporidiosis has been described to last approximately 2 weeks 
(Chen et al 2002), but can persist for longer (Mac Kenzie et al 1994). Other symptoms can 
include weight loss, abdominal pain, anorexia, fatigue, cramps, headache, fever, and vomiting 
(Painter et al 2015). Some healthy individuals may remain asymptomatic after exposure. In this 
Controlled Human Infection Model (CHIM) study, Cryptosporidium parvum will be used. Post-
infectious irritable bowel syndrome has been described in patients with enteritis due to bacterial 
pathogens such as Campylobacter, Salmonella or Shigella (Ozgül et al 1999). Seronegative 
reactive arthritis, including Reiter’s syndrome, and relapse in Crohn’s disease and ulcerative 
colitis have also been reported (Cron and Sherry 1995, Colussi et al 2010). In one study, 
persistent gastrointestinal symptoms were reported up to 25-36 months post-infection 
(Insulander et al 2013). Interpretation of self-reported data from outbreak-associated cohorts 
requires caution given the potential for bias towards those most adversely affected and those 
who attributed post-acute symptoms to acute cryptosporidiosis. Long-term sequelae have not 
been described in CHIM studies.

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Currently, nitazoxanide (Alinia®) is the only drug approved by the United States Food and Drug 
Administration for the treatment of cryptosporidiosis. The drug is indicated for treatment of 
diarrhea caused by C. parvum in patients 1 year of age and older. However, nitazoxanide has 
not been shown to be effective for the treatment of diarrhea caused by C. parvum in HIV-
infected or immunodeficient patients (Romark 2017). As the global competitive drug discovery 
landscape in cryptosporidiosis is sparse, there is an urgent need to identify new compounds that 
directly inhibit Cryptosporidium.
The goal of this study is to develop a method for establishing a reproducible and controlled 
Cryptosporidium infection in healthy adults that temporarily results in symptoms of 
cryptosporidiosis and is expected to resolve naturally within approximately 7-21 days. A 
healthy volunteer CHIM study is expected to allow for a careful, early examination of the 
pharmacokinetic-pharmacodynamic (PK-PD) relationship of a future investigational drug in a 
controlled setting, providing valuable data that informs future trial designs (Darton et al 2015, 
Pollard et al 2012). In contrast to real-world settings, participants in a cryptosporidiosis CHIM 
will have diarrhea due to a single pathogen, not potentially multiple ones. This will allow for 
unbiased interrogation of the effect of an investigational drug on clinical and parasitological 
endpoints. The safety and feasibility of controlled human Cryptosporidium parvum studies are 
well 
documented 
in 
the 
literature 
(Chappell et al 2006, 
DuPont et al 1995, 
Okhuysen et al 1999). If successful, this CHIM methodology would be used in the future (with 
different study participants) to enable assessment of novel therapies and vaccines for the 
treatment and prevention of cryptosporidiosis. A Cryptosporidium CHIM will provide 
important data demonstrating the prospect of benefit and informing dose selection of new 
therapies and vaccines before they are tested in vulnerable pediatric populations.
1.2
Purpose
The goal of this Phase I CHIM study will be to determine if oral administration of a Good 
Manufacturing Practice (GMP) supply of C. parvum oocysts (ABO809) to healthy volunteers 
results in Cryptosporidium infection and diarrheal illness. The study will measure fecal 
Cryptosporidium oocysts (parasitological endpoint) as well as diarrhea and associated signs and 
symptoms (clinical endpoint).
It is expected that approximately 90-100 percent of participants receiving ABO809 may become 
infected. The incidence of diarrheal illness will also be evaluated and may be somewhat lower 
than the incidence of infection.
This study, if successful, would enable a robust CHIM model that can be used in future studies 
to evaluate the efficacy of novel therapies and vaccines for the treatment and prevention of 
Cryptosporidium infection in healthy participants before they are assessed in the pediatric target 
population.

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2
Objectives and endpoints
Table 2-1
Objectives and related endpoints
Objective(s)
Endpoint(s)
Primary objective(s)
Endpoint(s) for primary objective(s)

To evaluate the incidence of 
Cryptosporidium infection following an 
oral administration of ABO809

Cryptosporidium infection as indicated by 
Cryptosporidium oocysts in fecal samples 
measured by EIA 
 
 at ≥72 hours post-administration (or 
sooner if associated with symptoms of diarrheal 
illness) up to Day 10 (inclusive).
Secondary objective(s)
Endpoint(s) for secondary objective(s)

To evaluate the incidence and 
characteristics of diarrheal illness 
following an oral administration of 
ABO809 

Presence of clinical diarrheal illness by Day 10 
(inclusive) and Day 28

Number of diarrhea episodes

Stool weight

Grading of stool consistency

Time to onset and time to resolution of diarrheal 
illness

Characteristics of clinical signs and symptoms 
associated with clinical diarrheal illness such as 
(abdominal pain, abdominal cramping, nausea, 
vomiting, fever, electrolyte imbalance, 
dehydration) up to Day 28

Cryptosporidium infection as indicated 
by Cryptosporidium oocysts in fecal samples 
measured by EIA 
 
 at ≥72 hours post-administration (or 
sooner if associated with symptoms of diarrheal 
illness up to Day 28)

To evaluate the time to onset and 
resolution of Cryptosporidium infection 
in participants who developed an 
infection following an oral 
administration of ABO809 

Detection of fecal shedding of C. parvum oocysts 
by EIA 
 up to 28 
days after administration of ABO809

Time to onset and time to resolution 
of Cryptosporidium infection following an oral 
administration of ABO809

To assess the safety and tolerability of 
ABO809

Adverse events, vital signs, ECG findings, safety 
laboratory assessments including chemistry, 
hematology, and urinalysis results up to and 
including the Day 28 visit

Adverse events of special interest by telephone 
follow-up after Day 28 through 12 months after 
ABO809 administration
Exploratory objective(s)
Endpoint(s) for exploratory objective(s)
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Objective(s)
Endpoint(s)
3
Study design
This Phase 1 Cryptosporidium CHIM study employs a single-center, open-label design to 
characterize the incidence of infection and associated symptoms following the administration 
of single doses of C. parvum oocysts (ABO809).
The study will enroll healthy volunteers in cohorts of approximately 10 participants who will 
receive ABO809 on the same day. A dose level group will receive the same ABO809 dose and 
can be comprised of multiple cohorts. The first dose level group will start with a cohort of 10 
participants who will receive ABO809 at a dose of 1x104 oocysts. The study will continue to 
enroll participants in the same dose level group if the desired incidences of infection and 
diarrheal illness are observed, up to a total of approximately 30 participants. If the desired 
incidences of infection and diarrheal illness are not observed, a new dose level group, receiving 
ABO809 at a dose of 1x106 oocysts, may be initiated. If needed to optimize the model, 
intermediate ABO809 doses may be evaluated (see Section 6.5).
The study will consist of three (to a maximum of six) sequential cohorts of approximately 10 
participants each. The cohorts will be dosed one after the other for a total of 30 (to a maximum 
of approximately 60) participants. This is an adaptive study and for a particular cohort, safety, 
incidence of infection and incidence of clinical illness will be evaluated on Day 14 to inform 
whether the ABO809 dose needs to be changed for dosing of the next cohort (see Section 6.5.1). 
If there are no safety issues, and the expected incidence of infection and illness are observed in 
one cohort, the next cohort will be dosed at the same dose level (see Section 6.5.1 for details). If 
the dose of ABO809 is changed from one cohort to the next, additional cohorts may be added 
to further evaluate Cryptosporidium infection and clinical illness following dosing with 
ABO809.
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The study will consist of up to a 28-day Screening/Baseline period, an ABO809 administration 
and inpatient monitoring period, an outpatient follow-up period, and a study completion 
evaluation on Day 56. Additionally, Post-Study Follow-Up Calls will be conducted at 6 and 12 
months after ABO809 administration. A CHIM diary will be provided to each participant to 
collect information on the participant's clinical symptoms.
Participants will receive a single oral dose of ABO809 on Day 1.
Cryptosporidium infection is defined as the presence of oocysts in at least 1 stool sample 
starting 72 hours following the administration of ABO809 (or sooner if associated with 
symptoms suggestive of diarrheal illness) and up to Day 10.
If clinical symptoms associated with cryptosporidiosis occur earlier than 72 hours post-
administration, then stool samples after the onset of symptoms can be collected for 
parasitological evaluation for the primary endpoint. Normal bowel transit time varies from 30 
to 40 hours, and therefore ≥72 hours is chosen to minimize the chance of detecting only 
passively excreted oocysts given orally.
Resolution of Cryptosporidium infection is defined as no evidence of Cryptosporidium in stool 
samples collected over ≥2 consecutive days.
Stool samples will also be collected and sent to the laboratory in instances of relapse symptoms 
suggestive of Cryptosporidium infection until Day 28. Participants experiencing diarrheal 
symptoms between Day 28 and Day 56 may return for an unscheduled visit and provide stool 
for assessment of Cryptosporidium infection.
A participant will be considered as showing clinical diarrheal illness if diarrhea is observed with 
at least two diarrheal bowel events within 24 hours on at least two days during the observation 
period beginning after the ABO809 administration (Day 1) and ending on Day 28 (see 
Section 8.3.2)
Resolution of diarrheal illness from Cryptosporidium infection requires ≥2 consecutive days 
with no diarrheal stools (stool sample grades 1 or 2).
Participants will be monitored daily for infection (parasitological evaluation) and diarrheal 
illness (clinical evaluation) during the domicile period. The monitoring of symptoms will 
continue in the outpatient setting with the collection of information via the CHIM diary and 
Safety Follow-Up Calls. Participants will provide a health and stool update daily from Day 1 
through 28 in the CHIM diary. Safety Follow-Up Calls will occur on Days 35, 42, 49, and 56. 
The primary endpoint is Cryptosporidium infection as indicated by detection of oocysts in fecal 
samples by EIA 
 ≥72 hours 
following an oral administration of ABO809 (or sooner if associated with symptoms suggestive 
of diarrheal illness). Secondary endpoints include characterization of diarrheal illness, safety 
and tolerability.
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Figure 3-1
Study Design
3.1
Screening/Baseline Period
After written informed consent has been obtained, healthy participants 18 to 50 years of age 
will be enrolled and educated about Cryptosporidium and its potential effects in humans. 
Following the provision of consent, volunteers will then take a written quiz to ascertain their 
level of understanding about the characteristics of Cryptosporidium infection, its transmission 
and appropriate safety precautions to avoid secondary infection. Participants who score 100% 
on the quiz and meet the eligibility criteria at Screening can advance in the study to receive one 
dose of ABO809. Participants will have the opportunity to retake the quiz. The quiz should be 
repeated before any additional screening assessments are obtained.
3.2
ABO809 administration and inpatient monitoring period
ABO809 will be administered at the study site on Day 1. All participants, whether or not they 
are symptomatic, will be domiciled in a unit with adequate infection control until completion 
of Day 10 assessments. Participants who experience symptoms will remain domiciled for the 
duration of the diarrheal illness up to a maximum of Day 21. After Day 10, participants will be 
released from the study site only after they have had no diarrheal stools for at least 24 hours. 
Signs, symptoms, stool characteristics and parasitological assessment of oocyst shedding will 
be monitored daily. Safety assessments will include physical exams, ECGs, vital signs, standard 
clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), adverse event 
and serious adverse event monitoring (see Table 8-1).
3.3
Follow-up period and End of Study
Participants will return for outpatient follow-up visits on Day 14, 17, 21, 24, and 28 for clinical 
assessments and to provide collected stool samples for analysis. To minimize the risk of long 
term asymptomatic shedding and recurrence, participants may receive nitazoxanide per the U.S. 
Prescribing Information (see Section 6.2.3).
If a participant experiences diarrhea after Day 10 (after the participant has been discharged from 
the study site), the participant may be readmitted, at the discretion of the Investigator, to remain 
domiciled until the cessation of symptoms or Day 21, whichever is earlier. If diarrhea is not 
associated with any additional risks to participants, the Investigator can decide that the 
participant can be managed in an outpatient setting. In this case, the participant is requested to 
make a reasonable effort to collect all diarrheal stool samples for delivery to the study site. If a 
participant is still experiencing diarrheal illness at Day 28, the participant's stool will be 
analyzed for ongoing shedding of oocysts and the participant may be referred to specialty care 
for further diagnostic work-up and treatment at the discretion of the Investigator.

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All participants will return for a follow-up visit on Day 28 to provide collected stool samples. 
A physical examination and laboratory tests will also be conducted.
 
 
 
 
 
 
 
 
 Alternatively, between 
Day 28 and Day 56, participants may seek medical support from his/her healthcare provider 
(HCP). Participants may come back to the study site for an unscheduled visit until EOS. The 
end of study (EOS) visit will occur on Day 56 via phone call. Additional Post-Study Follow-
Up phone calls will be conducted after EOS at 6 and 12 months after ABO809 administration. 
During the phone calls, data will be collected on the development of new onset persistent 
symptoms that may be related to administration with ABO809, including but not limited to 
diarrhea, abdominal pain, eye pain and joint pain in all participants (see Section 10.1.1.1).
4
Rationale
4.1
Rationale for study design
Randomization and blinding: All participants will receive ABO809 with a dose escalation 
strategy (see Section 6.5.1). Therefore the study is not randomized and is not 
blinded. Participants will be informed about the nature of Cryptosporidium infection and 
potential for asymptomatic infection in healthy adults. The likelihood of potential bias in 
reporting gastrointestinal symptoms will be mitigated by education of participants prior to 
enrollment in the study. A residual risk of bias remains in terms of reporting of anticipated 
symptoms (e.g. abdominal pain, nausea), however, the primary endpoint of oocysts detected in 
stool samples is objective. Similarly, diarrhea as the expected cardinal symptom of 
cryptosporidiosis in this study population is at little risk to be confounded by bias. Bias in 
efficacy endpoints will also be mitigated by having standardized clinical assessments to grade 
diarrhea and associated symptoms. The use of a central laboratory and validated assays will 
further decrease bias in safety and efficacy assessments.
ABO809 administration and Inpatient Follow-Up periods: To fully characterize the clinical 
course of disease, participants will remain domiciled and monitored for safety and study 
endpoints for 10 days after ABO809 administration. Participants will be discharged from the 
study site on Day 10 if diarrheal symptoms have been resolved for ≥24 hours. If clinical 
symptoms still persist on Day 10, the domicile period will be extended until the participant is 
free of clinical symptoms for ≥24 hours. Based on published data from previous CHIM studies 
conducted with strains of C. parvum and other Cryptosporidium species, the median incubation 
period from time of administration to the onset of diarrhea ranges from 3-11 days, with a median 
duration of diarrhea ranging from 2.3 to 7 days (see Table 4-1). It is expected that up to 30% or 
greater of healthy participants may remain asymptomatic after ABO809 administration. If 
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diarrhea persists at the Day 28 visit, the participant may be referred to specialty care for further 
diagnostic work-up and treatment at the discretion of the Investigator. A participant can be 
referred to specialty care earlier at the clinical judgement of the Investigator. This precautionary 
procedure will be implemented as it is possible that an underlying, previously 
undetected/unknown condition could contribute to continuing clinical symptoms. In previous 
CHIM studies, all participants experienced resolution of symptoms and were able to clear 
Cryptosporidium infection.
Outpatient follow-up period: After the domicile period, participants will be followed on an 
outpatient basis ending on Day 56 following the ABO809 administration. Infection is expected 
to be self-limiting in healthy adults and resolve by Day 21. Published literature on the intensity 
of infection and oocyst excretion patterns of C. parvum in healthy volunteers suggests that 
oocyst excretion is limited to the first 14 days in up to 86% participants with diarrhea, and 
excretion prolonged beyond 28 days is observed in only 5% of participants 
(Chappell et al 1996). Participants will return for follow-up visits on Day 14, 17, 21, 24 and 28 
for physical examination and/or to provide collected stool samples (for measurement of oocyst 
shedding) (see Table 8-1). Safety Follow-Up Calls will be conducted with participants up to 
Day 56 to collect adverse events that are considered related to administration with ABO809 
(see Section 10.1.1.1). Any participants who experience diarrheal symptoms between Day 28 
and Day 56 may provide a stool sample for analysis and may return to the study site for an 
unscheduled visit to consult with the Investigator.
Treatment with nitazoxanide: Nitazoxanide is a safe and well-tolerated drug approved in the 
United States to treat diarrhea caused by Cryptosporidium parvum. In a 2015 C. muris challenge 
study, two subjects with persistent oocyst shedding were successfully treated with nitazoxanide 
and the infection was resolved in both subjects, demonstrating the potential of nitazoxanide as 
a rescue drug (Chappell et al 2015). Following resolution of diarrhea, C. parvum infection may 
be associated with shedding of oocysts with a 21% relapse rate as suggested by the 1993 
Milwaukee outbreak (MacKenzie et al 1995). Participants who develop an infection (i.e. oocyst 
shedding), with or without clinical symptoms will receive a standard 3-day course of 
nitazoxanide treatment per the U.S. Prescribing Information on Day 21. Given the variability 
in the onset and duration of oocyst shedding and clinical symptoms in healthy adults, 
administering nitazoxanide on Day 21 is considered appropriate to enable the full 
characterization of the study endpoints. Nitazoxanide may be administered earlier, based on 
clinical findings (see Section 3.3 and Section 6.2.3). Once initiated, nitazoxanide treatment is 
expected to decrease or eliminate any persistent oocyst shedding to safeguard participants, their 
household contacts and public health interests. Participants will be informed about reasons of 
nitazoxanide treatment to improve compliance, which will be recorded in a participant diary. 
Although nitazoxanide has proven efficacy in reducing oocyst shedding and acute diarrhea in 
80-93% of treated participants, there have been no studies looking at the effect of nitazoxanide 
on the incidence of long-term oocyst shedding or sequelae of cryptosporidiosis. Given this 
background, Safety Follow-Up Calls will be conducted up to Day 56.
Adaptive study design: The goal is to maximize the incidence of infection. The study cohorts 
of approximately 10 participants each are designed to enable domiciling of participants in an 
inpatient unit with adequate infection control, isolation and monitoring. Cohorts are sequential 
to enable adjustment of the ABO809 dose from one cohort to the next for efficacy and safety 
reasons. After the Day 14 visit, a Dose Adjustment Data Review will be conducted for the 

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cohort (see Section 6.5.1) and may result in a dose adjustment for the subsequent cohort. The 
dose may be adjusted upward to increase the incidence of infection and clinical symptoms or 
may be reduced due to safety concerns.
End of the Study (EOS): For each participant, the study will end at the Day 56 visit. Additional 
Post-Study Follow-Up phone calls will be conducted after EOS at 6 and 12 months after 
ABO809 administration.
4.2
Rationale for dose/regimen and duration of treatment
A total of 10 publications have described CHIM studies conducted with a number of 
Cryptosporidium isolates, including C. parvum, C. hominis, C. meleagriditis, and C. muris, with 
the first study conducted more than two decades ago. These studies aimed to confirm the 
infectivity of various Cryptosporidium species in humans, to identify the human infectious dose, 
or to explore mechanisms of pathogenesis. Sample size across these published studies is small. 
The median infectious dose (ID50) among these various C. parvum isolates range from 100 to 
5,000 oocysts. For the studies conducted with the C. parvum Iowa strain in naive patients 
(seronegative), 100% infectivity (defined by positive detection of oocysts shed in stools) was 
observed in participants who had received an administration of ≥103 oocysts. The highest dose 
administrated in these studies was 106 oocysts. No safety concerns, other than the expected 
diarrheal illness associated with Cryptosporidium infection, were reported for any of the doses 
or species used for these CHIM studies. No clear relationship between the number of oocysts 
administered and the presence or severity of clinical syndromes has been described. While the 
link between the occurrence of diarrhea and size of the inoculum is unclear from published 
CHIM studies, increasing the size of the inoculum may produce more consistent clinical and 
parasitological outcomes in a larger proportion of participants.
This CHIM study seeks to safely maximize the incidence of infection and clinical symptoms, 
and based on the published data, an adaptive study design will be utilized to evaluate oocyst 
doses of approximately 104 up to 106 oocysts. The clinical dose is prepared using the most 
recent available % viability stability data per clinical batch. An administration of 104 oocysts 
has been selected for the first dose-level, and an initial 10 participants will be dosed in cohort 1 
at this dose-level. This dose is expected to establish an infection resulting in shedding 
of Cryptosporidium oocysts in the majority of participants, however, the occurrence of clinical 
symptoms may occur at a lower incidence. If no safety issues are encountered and the desired 
incidence of infection or clinical diarrheal illness is not achieved (see Section 6.5.1), the 
anticipated next dose-level is approximately 106 oocysts (see Table 6-2). If the clinical 
symptoms occur at the desired incidence and no safety concerns are observed, additional cohorts 
will be added to the same dose level. Previously, 106 oocysts have been shown to be safe 
(DuPont et al 1995), however only small numbers of participants (n=7) received doses ≥1000 
oocysts. As 106 oocysts has been the largest dose administered in previous CHIM studies, no 
higher dose of ABO809 is considered for this study. Since administration of 106 oocysts was 
not associated with safety concerns, it is considered acceptable to escalate the dose level from 
104 to 106 without intermediate dose levels. This will support reaching the maximally obtainable 
incidence of infection in a Cryptosporidium CHIM with the fewest number of participants 
enrolled. In the unlikely event of safety concerns associated with any dose, a lower dose may 
subsequently be used. This dose will be approximately 1 log lower than the previous dose in 
which safety concerns were noted. Dosing steps between 0.5 and 1 log were used in previous 

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CHIM studies (see Table 4-1). However, to our knowledge no dose reduction was required at 
any time in any of these previous CHIM studies since no safety concerns were observed. Since 
doses of <103 oocysts did not consistently lead to infection in previous studies (see Table 4-1), 
a dose lower than approximately 103 oocysts is not currently considered for this study.
Details of the dose escalation scheme are provided in Section 6.5.1.
Table 4-1
CHIM studies with C. parvum
Species
Dose
N 
Infection 
rate (%)
Diarrhea 
incidence 
(%)
Diarrhea 
incubation 
(days)
Diarrhea  
duration 
(hours) 
C. parvum Iowa1
30-106
29
20-100
0-38
6.5 da
74 hb
C. parvum Iowa2
5x102
19
84
58
8.2 db
60 hb
C. parvum Iowa3
5x102-5x104
17
41
59
5 da
155 ha
C. parvum UCP4
5x103-104
20
44-100
56-75
6 da 
56 ha
C. parvum Iowa, 
UCP, TAMU5
10-105
60
20-100
52-86
5-11 db 
64-95 hb
C. parvum Iowa, 
TAMU6
102-103
15
50-67
33-83
n/a
n/a
aexpressed as median value
bexpressed as mean value
1 DuPont et al 1995, 2Okhuysen et al 1998a , 3Chappell et al 1999, 4 Okhuysen et al 1998b, 
5 Okhuysen et al 1999, 6 Alcantara et al 2003 
4.3
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs
Not applicable
4.4
Purpose and timing of interim analyses/design adaptations
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4.5
Risks and benefits
There is no benefit expected for participants enrolling in this study. All participants will receive 
thorough medical examinations.
A majority of participants (up to 100% based on prior data) are expected to develop 
Cryptosporidium infection after an oral administration of C. parvum. Development of diarrheal 
illness has been highly variable in previous CHIM studies (see Table 4-1). In one study, 100% 
of healthy volunteers (n=7) receiving ≥1000 C. parvum oocysts, i.e. approximately 10 times 
above ID50 (median infective dose) developed infection as measured by fecal oocyst shedding; 
71% had enteric symptoms, but of these only 29% had diarrheal illness (DuPont et al 1995). 
The Iowa strain of C. parvum used in this study has been suggested to be associated with the 
shortest duration of diarrhea in comparison to the TAMU and UCP strains 
(Okhuysen et al 1999).
Cryptosporidiosis typically is a self-limiting infection in immunocompetent adults. The risk to 
healthy participants is derived from published literature of previous Cryptosporidium studies 
(see Table 4-1), our understanding of the natural history of Cryptosporidium infection in 
healthy adults, and known complications of severe infectious and non-infectious diarrheal 
illness. Potential risks include:

Gastrointestinal cryptosporidiosis: Cryptosporidium can cause asymptomatic infection, 
mild diarrhea, or severe enteritis with or without biliary tract involvement. Asymptomatic 
infections have been observed in immunocompetent adults and children with natural 
infection. This is substantiated in healthy adult human challenge studies, for subjects 
receiving >1000 oocysts (n=7), 71% had enteric symptoms, but of these only 29% had 
diarrheal illness (DuPont et al 1995) (see Table 4-1). Diarrhea associated with 
cryptosporidiosis may be acute or chronic; transient, intermittent or continuous; and scant 
or voluminous, with up to 25 L/day of watery stool. Patients who develop frequent 
diarrhea may experience associated malaise, nausea and anorexia, crampy abdominal pain, 
and low-grade fever. In healthy adults, the illness usually resolves without therapy in 10 to 
14 days, although it can persist longer or relapse after initial improvement. Moderate to 
severe diarrheal illness and associated complications may occur, including but not limited 
to persistent vomiting, abdominal pain, dehydration, acute renal failure. The risk of severe 
and/or prolonged disease is increased in patients with cellular and humoral immune 
deficiencies (e.g. AIDS, organ transplantation, IgA deficiency, hypogammaglobulinemia, 
and receipt of immunosuppressive therapy); all participants with these conditions will be 
excluded from the study.
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
Extraintestinal cryptosporidiosis and extraintestinal symptoms of cryptosporidiosis: 
A number of other clinical manifestations of cryptosporidiosis have been described in 
patients with AIDS and prolonged disease. Clinical manifestations can include 
cholecystitis, cholangitis, hepatitis, and pancreatitis (Chalmers and Davies 2010). 
Pulmonary involvement has also been described, but it is unclear whether 
Cryptosporidium is a true pathogen or merely colonizes the respiratory tract. Nonspecific 
respiratory symptoms, including cough, have been reported. Disseminated 
cryptosporidiosis has not been described. Extraintestinal manifestations, as observed in 
AIDS patients (Lopez-Velez et al 1995), are expected to be rare in healthy adults. 
Extraintestinal symptoms of cryptosporidiosis have been reported in immunocompetent 
patients: it has been suggested that C. parvum (used in this study) is less associated with 
occurrence of non-intestinal sequelae (joint and eye pain, recurrent headache, dizzy spells, 
fatigue) than C. hominis (Hunter et al 2004a) but this is not uniformly reported 
(Igloi et al 2018). Extraintestinal symptoms of cryptosporidiosis had already occurred 
more frequently among cases even before infection with Cryptosporidium as compared to 
what was observed in population controls. Hence, people acquiring cryptosporidiosis may 
be a particular group of the population with a generally increased susceptibility to illness 
(e.g. people with underlying chronic conditions) (Igloi et al 2018). In this study, 
participants with chronic/recurring gastrointestinal symptoms will not be enrolled. 
Extraintestinal manifestations in immunocompetent healthy adults have not been 
described in the published Cryptosporidium human challenge studies (see Table 4-1). 

Persistent/recurrent illness and non-intestinal sequelae/post-infectious syndromes: 
After resolution of the acute infection, longer-term health effects have been described in 
longitudinal studies of adult outbreak-associated cryptosporidiosis. Self-reported post-
infection symptoms up to 12 months included weight loss, abdominal pain, diarrhea, eye 
pain, joint pain, fatigue, and symptoms consistent with irritable bowel syndrome 
(Stiff et al 2017). A case-control study found that infection with C. hominis (but not C. 
parvum) was associated with joint pain, eye pain, headaches, and fatigue during the two 
months after infection (Hunter et al 2004b). While there was no difference between C. 
parvum and C. hominis infection with regard to post-infectious irritable bowel syndrome, 
fatigue and abdominal pain were reported more frequently after C. hominis infection than 
after C. parvum infection within 1 year after acute infection (Carter et al 2019). Based on 
this information, participants may continue to have symptoms after resolution of acute 
infection. In immunocompetent hosts, persistent gastrointestinal and joint symptoms (e.g., 
painful and inflamed joints involving the knees, ankles, and feet) after natural infection 
can last for many months after the initial infection (Carter et al 2019, Rehn et al 2015) and 
may be related in part to the specific species that is causing infection. None of these health 
concerns have been described in any of the previously conducted Cryptosporidium CHIM 
studies (see Table 4-1). It is not known whether treatment with nitazoxanide may further 
decrease any potential risk.

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
Potential adverse events from Nitazoxanide therapy: Nitazoxanide (Alinia®) will be 
administered to all participants with Cryptosporidium positive stool and/or clinical 
symptoms on Day 21. Nitazoxanide may be administered earlier to participants with 
persistent diarrhea on or after Day 10 to resolve diarrheal illness and minimize the risk of 
shedding or recurrent disease. To avoid unnecessary medication, participants without 
oocyst shedding at any time after Day 3 and without any diarrhea between Day 1 and Day 
21 and without household contacts with diarrhea between Day 10 and Day 21 will not 
receive nitazoxanide. Nitazoxanide may also be administered as part of "rescue 
medication" to treat severe diarrheal illness before Day 10 (see Section 6.2.3). The most 
common adverse reactions in ≥2% of patients were abdominal pain, headache, 
chromaturia and nausea. In placebo-controlled clinical trials using the recommended dose 
of nitazoxanide, the rates of occurrence of these events did not differ significantly from 
those of the placebo. In controlled trials of patients age 12 years and older who received 
nitazoxanide for the treatment of diarrhea caused by Giardia lamblia or C. parvum, less 
than 1% of patients discontinued therapy because of an adverse event (Romark 2017). In 
the unlikely event that symptoms persist, the participant will, at the discretion of the 
Investigator, obtain additional diagnostic work-up and subsequent therapy (potentially 
including a second course of nitazoxanide) as appropriate (see Section 6.2.3).
The risks to participants in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close monitoring. Refer to the Investigator's Brochure.
4.5.1
Blood sample volume
A volume smaller than a typical blood donation will be collected during the Screening/Baseline, 
Inpatient Follow-Up and Outpatient Follow-Up portions of the study (up to 8 weeks total). 
Additional samples may be required for safety monitoring. The timing and intended use of 
blood samples is outlined in the Assessment Schedule (see Table 8-1). Instructions for sample 
collection, 
processing, 
storage 
and 
shipment 
information 
are 
available 
in 
the Laboratory Manual. See Section 8.5.1.2 on the potential use of residual blood samples.
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4.6
Rationale for Public Health Emergency mitigation procedures
During a Public Health emergency as declared by Local or Regional authorities (i.e. pandemic, 
epidemic or natural disaster), mitigation procedures to ensure participant safety and trial 
integrity are listed in relevant sections. Notification of the Public health emergency should be 
discussed with Novartis prior to implementation of mitigation procedures, and 
permitted/approved by Local or Regional Health Authorities and Ethics Committees as 
appropriate.
5
Study Population
The study population will be comprised of adult male and female healthy participants. Up to 
approximately 60 participants may be enrolled in the study.
The Investigator must ensure that all participants being considered for the study meet the 
following eligibility criteria. No additional criteria should be applied by the Investigator, in 
order that the study population will be representative of all eligible participants.
Participant selection is to be established by checking through all eligibility criteria at Screening 
and Baseline. A relevant record (e.g. checklist) of the eligibility criteria must be stored with the 
source documentation at the study site.
Deviation from any entry criterion excludes a participant from enrollment into the study. See 
Section 9.1.1.1 for information on replacement participants.
5.1
Inclusion criteria
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent from the participant must be obtained prior to participation in the 
study.
2. At Screening, participants will be educated on facts about Cryptosporidium disease, safety 
measures and transmission risks. Participants must then score 100% on a quiz assessing 
their understanding of Cryptosporidium infection and transmission. Participants will have 
the opportunity to retake the quiz. The quiz should be repeated before any additional 
Screening assessments are obtained.
3. Male and female participants must be between 18 to 50 years of age and in good health as 
determined by medical history, physical examination, vital signs, electrocardiogram, and 
laboratory tests at Screening and Baseline.
4. At Screening and Baseline, vital signs will be assessed in the sitting position, and must be 
within the following ranges:

oral body temperature between 35.0-37.0 oC

systolic blood pressure between 90-139 mmHg

diastolic blood pressure between 59-89 mmHg

pulse rate between 50-90 bpm
5. Participants must weigh at least 50 kg, and have a body mass index (BMI) within the 
range of 18-30 kg/m2. 

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6. Ability to communicate well with the Investigator, and to understand and comply with the 
requirements of the study including restrictions provided in Section 6.2.4.
7. Participant must be in compliance with current local COVID-19 testing policies.
5.2
Exclusion criteria
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
No additional exclusions may be applied by the Investigator, in order to ensure that the study 
population will be representative of all eligible participants.
1. History of Cryptosporidium infection.
2. Current (based on screening laboratory tests) or history of infectious diarrhea associated 
with international travel in the last 12 months or C. difficile infection within 6 months 
prior to Screening.
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6
Treatment
6.1
Study treatment
Details on the requirements for storage and management of study treatment, and dispensing and 
taking study treatment will be outlined in the Pharmacy Manual. If vomiting occurs within 30 
minutes of administration of ABO809 a second administration of ABO809, at the same dose 
may be given.
6.1.1
Investigational and control drugs
Table 6-1
Investigational drug
Investigational Drug 
(Name and Strength)
Pharmaceutical 
Dosage Form
Route of 
Administration
Supply Type
ABO809, 3x106 CE/3 
mL
Concentrate for oral 
suspension
Oral use
Open label bulk 
supply; glass vials
CE, C. parvum oocysts
No control drug will be used in this study.
6.1.2
Additional study treatments
Participants may receive nitazoxanide (see Section 6.2.3).
Table 6-2
Additional Study Treatment
Drug
(Name and Strength)
Pharmaceutical 
Dosage Form
Route of 
Administration
Supply Type
Nitazoxanide 500 mg
Tablet
Oral use
Bottle
Nitazoxanide to be provided by clinical site
6.1.3
Supply of study treatment
Refer to Pharmacy Manual.
6.2
Other treatment(s)
Participants may receive nitazoxanide and/or other treatments as detailed below.
6.2.1
Concomitant therapy
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant is enrolled into the study must be recorded 
on the appropriate Case Report Forms. Fluid replacement (e.g. as needed with diarrheal 
symptoms) will be recorded as a concomitant medication.
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Each concomitant medication must be individually assessed against all exclusion 
criteria/prohibited medication. If in doubt, the Investigator should contact the Novartis medical 
monitor before administering a new medication.
6.2.2
Prohibited medication
Except for protocol allowed concomitant medication or any medication which may be required 
to treat adverse events, no medication other than study treatment will be allowed from the date 
the participant signs the inform consent until EOS.
Participants should not receive any antiperistaltic, antidiarrheal agents or stool softeners from 
Screening through Day 28. These agents include, but are not limited to, bismuth subsalicylate, 
atropine and diphenoxylate, loperamide, octreotide, opium tincture, cholestyramine, colestipol, 
colace, or lactulose. Participants should not consume yogurt, kefir or probiotics (e.g. 
Saccharomyces boulardii) up to Day 21 or initiation of nitazoxanide, whichever comes first. 
All medications, procedures and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant is enrolled into the study must be recorded 
on the appropriate Case Report Forms.
In addition, other than those administered per protocol, participants should not receive any 
antibacterial or anti-parasitic therapy with possible activity against Cryptosporidium up to Day 
28 (see Section 6.2.3).
Warfarin or drugs that prolong the QTc interval are not permitted between Screening and Day 
28 unless deemed necessary by the Investigator (participants on warfarin or drugs that prolong 
the QTc interval are not permitted to enter the study (see Section 5.2).
Vaccinations are not permitted between Day -14 and Day 28 but are permitted outside this 
window (including COVID-19 vaccinations).
6.2.3
Rescue medication
To minimize the risk of severe clinical illness, long-term asymptomatic shedding and recurrence 
of Cryptosporidium infection, nitazoxanide may be administered at 500 mg by mouth every 12 
hours with food for 3 days as per the U.S. Prescribing Information, under the clinical conditions 
outlined below. Nitazoxanide is the standard of care for the treatment of cryptosporidiosis. In 
double-blind, controlled trials in adults and adolescents with diarrhea and with or without 
enteric symptoms caused by C. parvum, nitazoxanide administered at 500 mg BID for 3 days 
resulted in a 96% clinical response rate 4 to 7 days following the end of treatment. In this study, 
clinical response was defined as "no symptoms, no watery stools and no more than 2 soft stools 
within the past 24 hours" or "no symptoms and no unformed stools within the past 48 hours" 
(Romark 2017).
All participants who receive ABO809 and develop an infection (i.e. oocyst shedding after Day 
3), will receive nitazoxanide on Day 21 or as soon as EIA analysis 
 
 of Day 17 sample becomes available whether or not they develop clinical symptoms. 
There are conditions under which participants may receive nitazoxanide earlier: (i) participants 
with diarrhea persisting until Day 10 will start nitazoxanide on Day 10, (ii) participants with 
severe diarrheal illness (≥ Grade 3 as per Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007)) may receive 
CCI

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nitazoxanide unless deemed contraindicated by the Investigator irrespective of timing. 
Whenever nitazoxanide treatment is administered to participants experiencing clinical 
symptoms, participants may be domiciled at the discretion of the Investigator until free of 
clinical symptoms for ≥24 hours.
A second course of nitazoxanide and/or other antiparasitic drug(s) (e.g. paromomycin alone or 
in combination with azithromycin) may be considered for participants with severe diarrhea or 
treatment failure after nitazoxanide monotherapy at the discretion of the Investigator. The 
duration of treatment will depend upon the participant's response to therapy. Although 
controlled, large-scale trials are lacking, the use of combination therapy is supported by findings 
from small case series (Smith et al 1998). Paromomycin (500 mg three times daily for one 
week) is generally used as an alternative agent if nitazoxanide cannot be used. All antimicrobial 
therapy for cryptosporidiosis administered before Day 28 will be recorded in eCRF as a 
concomitant medication.
Participants will not receive nitazoxanide if:

they did not shed oocysts at any time after Day 3 and

they did not have diarrhea between Day 1 and Day 21 and

there was no diagnosis of cryptosporidiosis in any of the participant's household contacts 
between Day 11 and Day 21
In participants with severe diarrheal illness, oral and/or intravenous hydration, and replacement 
of electrolytes as needed, is expected as part of the standard of care management of adverse 
events (dehydration and severe diarrhea). Fluid replacement therapy will be recorded as a 
concomitant medication in the eCRF.
6.2.4
Restriction for study participants
Participants should be informed and reminded of the restrictions outlined in this section.
6.2.4.1
Dietary restrictions and smoking

No alcohol from Day-2 until after the Day 28 visit.

No cannabis use from Screening until after the Day 28 visit.

No cigarettes/use of nicotine products from Screening until the Day 28 visit.

Only thoroughly cooked meat, fish and seafood will be allowed from Day-4 until after the 
Day 28 visit (all meat must be "well done" so that no red is evident).

Participants should not consume yogurt, kefir or probiotics (e.g. Saccharomyces boulardii) 
up to Day 21 or initiation of nitazoxanide, whichever comes first.
Meals will be provided when all study procedures scheduled for that time have been completed.
6.2.4.2
Other restrictions

No strenuous physical exercise (e.g. weight training, aerobics, football) from Day 1 until 
discharged

Participants must abstain from using public pools and waterparks from Day 1 until after 
the Day 28 visit. Refraining from using private swimming pools is also recommended.

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
Employment as a healthcare worker with direct patient care, in a daycare center (for 
children or the elderly), or direct food handler (individuals who work directly with food in 
commercial establishments) is prohibited between Screening and Day 28.

Sharing a home with a pregnant woman or anyone <7 years old or >65 years old, infirmed, 
or immunocompromised is prohibited between Screening and Day 28.

Sexual practices that may increase the risk of fecal-oral transmission of Cryptosporidium 
should be avoided or appropriate safety measures used from Day 1 until after the Day 28 
visit. Participants will be informed about CDC recommendations to practice safer sex in 
case of cryptosporidiosis. 
(Parasites-Cryptosporidium-Prevention & Control-General Public 2019): 

Wait to have sex (vaginal, anal, and oral) for 2 weeks after you no longer have 
diarrhea.

Reduce your contact with stool during sex by: 

Washing your hands, genitals, and anus with soap and water before and after 
sexual activity

Using barrier methods during sex. Barrier methods include condoms, dental 
dams, and cut-open condoms. Sex includes oral (mouth-to-penis, mouth-to-
vagina, mouth-to-anus), anal (penis-to-anus), and vaginal (penis-to-vagina) sex

Using latex gloves during anal fingering or fisting

Using condoms the right way, every time you have anal and vaginal sex, which 
will also help prevent other sexually transmitted infections

Washing your hands with soap and water immediately after touching a used 
condom or other barrier method

Washing sex toys with soap and water after each use, and washing hands after 
touching used sex toys
Participants will receive educational material explaining all applicable restrictions and 
recommendations to avoid spread of Cryptosporidium oocysts.
6.2.4.2.1 Additional Recommendations
Handwashing Procedures
Alcohol-based sanitizers are not effective against Cryptosporidium. Use of good hygiene 
practices, especially washing hands with soap and water is essential, in particular at the 
following key times (When and How to Wash Your Hands 2020):

Before, during, and after preparing food

Before and after eating food

Before and after caring for someone who is sick with vomiting or diarrhea

Before and after treating a cut or wound

After using the toilet

After changing diapers or cleaning up a child who has used the toilet

After blowing your nose, coughing, or sneezing

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
After touching an animal, animal feed, or animal waste

After handling pet food or pet treats

After touching garbage

There can also be other times when it is important to wash hands
House-cleaning Procedures
Participants will be informed that Cryptosporidium is not sensitive to chlorine or bleach 
disinfectants and no disinfectant is completely effective against Cryptosporidium. The chance 
of spreading the infection can be lowered by recommended cleaning procedures, which will 
be provided to the participants:
(Parasites – Cryptosporidium – General Information for the Public)

Wash linens, clothing, dishwasher- or dryer-safe soft toys, etc. soiled with feces or vomit 
as soon as possible 

Flush excess vomit or feces on clothes or objects down the toilet 

Wash linens, clothing, etc. soiled with feces or vomit as soon as possible 

Use laundry detergent and wash in hot water (113°F or hotter for at least 20 minutes or 
122°F or hotter for at least 5 minutes) 

Machine dry on the highest heat setting  
For other household objects and surfaces: 

Remove all visible feces 

Clean with soap and water 

Let dry completely for at least 4 hours (if possible, expose to direct sunlight during the 4 
hours)
6.3
Participant numbering, treatment assignment, randomization
6.3.1
Participant numbering
Each individual may participate only once in this study and will be identified by a Participant 
Number (Participant No.) that will be assigned when the participant is enrolled for screening 
and will be retained for the participant throughout his/her participation in the study. A new 
Participant No. will be assigned at every subsequent enrollment if the participant fails screening 
and is re-screened. The Participant No. consists of the Center Number (Center No.) (as assigned 
by Novartis to the investigative site) with a sequential participant number suffixed to it, so that 
each participant’s participation is numbered uniquely across the entire database. Upon signing 
the informed consent form, the participant is assigned to the next sequential Participant No. 
available.
The informed consent procedures need to be re-started if the Investigator chooses to re-screen 
the participant after a participant has screen failed, and the participant will be assigned a new 
Participant No.
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6.4
Treatment blinding
Treatment will be open to participants, investigator staff, person performing the assessments 
and the Novartis clinical trial team (CTT).
6.5
Dose escalation and dose modification
Prior to any dose adjustment, a review of efficacy and safety/tolerability data in the dose cohort 
will be performed, in order to decide about dose escalation.
6.5.1
Dose escalation guidelines
Data to be reviewed for dose escalation
After each cohort, and prior to any dose adjustment for the subsequent cohort, a review of all 
available safety data will be performed to determine if it is safe to dose additional participants 
in subsequent cohorts.
The data to be reviewed to inform dose-adjustment include the incidence of clinical symptoms 
and the incidence of infection up to Day 10, as well as all available safety information including 
safety information obtained up to Day 14, AEs, safety laboratory assessments (hematology, 
chemistry, urinalysis), ECGs, vital signs, physical examination) for that cohort.
Criteria for dose escalation
The Sponsor and site Investigator will perform a joint Dose Adjustment Data Review after all 
participants in a cohort have completed the Day 14 visit, with the expectation that 10 
participants will provide evaluable data. Evaluable data is defined as data received from any 
participant who provided at least one stool sample for parasitological assessment and/or in 
whom we have a clinical evaluation of potential diarrheal illness via CHIM diary or AE 
reporting with at least two diarrheal bowel events within 24 hours after ≥72 hours post 
administration of ABO809. For definitions of infection and diarrheal illness, see Section 3. If 
there are no safety concerns that will prevent continuation of a given dose level or dose 
escalation, the dose escalation decision will be guided by the following criteria. If at the data 
review the criteria below are achieved, a subsequent cohort may be dosed at the current dose 
level:

There are approximately 80%-90% of participants showing infection

There are approximately 60%-70% of participants showing diarrheal illness
Otherwise, a dose escalation decision may be made. The decision will take into consideration 
the totality of data available at the time of decision making.
In the case of safety concerns associated with any ABO809 dose, the next cohort may be dosed 
with an inoculum approximately one order of magnitude smaller than the preceding one. For 
example, if safety concerns are noted in the cohort receiving an inoculum of approximately 106 
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oocysts, the next cohort of 10 participants may be dosed with an inoculum of approximately 105 
oocysts (see Section 6.5.1.2).
Safety Review Team
Participating functions (tasks can be delegated to appropriately qualified deputies) in all safety 
reviews include:

Sponsor 

medical lead

operational lead

research lead (optional)

statistician (optional)

biomarker expert (optional)

Study site 

Investigator

operational lead
Additional functions can be added on an ad-hoc basis.
For timing of safety data reviews see Section 4.4 (Purpose and timing interim analyses), 
Section 6.5.1 (Dose escalation), and Section 9.1.4 (Study stopping rules).
6.5.1.1
Starting dose
The starting dose to be administered to the first cohort of 10 participants will be a single dose 
of approximately 104 oocysts administered as oral suspension to be taken with approximately 
one glass of water (approximately 200 mL).
6.5.1.2
Provisional dose levels
Table 6-3 describes the starting dose and the maximum dose level that may be evaluated during 
this trial; additional doses between 1x103 and 1x106 may be considered.
Table 6-3
Provisional dose levels
Dose level
Oocyst dose (approximate viable oocyst 
count)
Starting dose
1x104
Maximum dose
1x106
6.6
Additional treatment guidance
6.6.1
Treatment compliance
Each participant will be supervised while receiving their single dose of ABO809, and will be 
domiciled for a minimum of 10 days to support compliance with study requirements.

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6.6.2
Recommended treatment of adverse events
Based on the expected symptomatology following Cryptosporidium administration, treatment 
to stabilize electrolyte and water homeostasis may need to be initiated. This may include 
parenteral fluid administration and, in case of persistent clinical symptoms, the administration 
of medications (see Section 6.2.3).
Any interventions to treat adverse events (AEs) must be recorded on the appropriate eCRF.
6.7
Preparation and dispensation
The study site will be supplied with ABO809 in packaging as described in the Investigational 
and control drugs section (see Section 6.1.1). A unique medication number will be printed on 
the study medication label. ABO809 should be prepared/diluted as per the instructions for use 
provided in the Pharmacy Manual.
6.7.1
Handling of study treatment and additional treatment
6.7.1.1
Handling of study treatment
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels.
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Corporate Organization Quality Assurance.
Medication labels will be in the local language and comply with the legal requirements of the 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number.
The Investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a Drug Accountability Log. Monitoring of drug accountability will be performed 
by monitors during site visits or remotely and at the completion of the trial. Participants will be 
asked to return all unused nitazoxanide and packaging at the end of the study or at the time of 
discontinuation of study treatment.
At the conclusion of the study, and as appropriate during the course of the study, the Investigator 
will return all unused study treatment, packaging, drug labels, and a copy of the completed Drug 
Accountability Log to the Novartis monitor or to the Novartis address provided in the 
Investigator folder at each site.
6.7.2
Instruction for prescribing and taking study treatment
Table 6-4
Dose and treatment schedule
Investigational / Control Drug
(Name and Strength)
Dose
Frequency and/or Regimen
ABO809, 3x106 CE/3m L
Approximate oocyst count 
1x103 - 1x106
A single dose on Day 1

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Investigational / Control Drug
(Name and Strength)
Dose
Frequency and/or Regimen
Nitazoxanide (Rescue 
medication)
500 mg
Every 12 hours with food for 3 
days
7
Informed consent procedures
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), IRB/IEC-approved Informed Consent.
Informed Consent must be obtained before conducting any study-specific procedures (e.g. all 
of the procedures described in the protocol). The process of obtaining Informed Consent must 
be documented in the participant source documents.
Novartis will review the study site proposed Informed Consent form to ensure it complies with 
the ICHE6 GCP guidelines and regulatory requirements and is considered appropriate for this 
study. Any further changes to the proposed consent form suggested by the Investigator must be 
agreed to by Novartis before submission to the IRB/IEC.
Information about common side effects already known about ABO809 and nitazoxanide can be 
found in Section 4.5, the Investigator's Brochure (IB) and the USPI for nitazoxanide. This 
information will be included in the participant Informed Consent and should be discussed with 
the participant during the study as needed. Any new information regarding the safety profile of 
ABO809 that is identified between IB updates will be communicated as appropriate, for 
example, via an Investigator notification (IN) or an aggregate safety finding. New information 
might require an update to the Informed Consent and must be discussed with the participant.
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e. pandemic, epidemic, or natural disaster, that may challenge the ability to obtain 
a standard written Informed Consent due to limits that prevent an on-site visit, Investigator may 
conduct the Informed Consent discussion remotely (e.g. telephone, videoconference) if 
allowable by a local Health Authority.
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g. the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining Informed Consent, etc.).
The following Informed Consents are included in this study:

Main study consent, which also includes: 

A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study

As applicable, Pregnancy Outcomes Reporting Consent for female participants or the 
female partners of any male participants who took study treatment
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Women of child-bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirements.
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval.
Participants may be asked to complete an optional questionnaire to provide feedback on their 
clinical trial experience.
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8
Visit schedule and assessments
The Assessment Schedule (Table 8-1) lists all of the assessments when they are performed. All data obtained from these assessments must be 
supported in the participant’s source documentation.
Participants should be seen for all visits/assessments as outlined in the Assessment Schedule (Table 8-1) or as close to the designated day/time 
as possible. Missed or rescheduled visits should not lead to automatic discontinuation.
Participants who discontinue from the study treatment are to return for the end of treatment visit as soon as possible, and attend the follow-up 
visits as indicated in the Assessment Schedule.
The “X” in the table denotes the assessments to be recorded in the clinical database or received electronically from a vendor. The “S” in the 
table denotes the assessments that are only in the participant’s source documentation and do not need to be recorded in the clinical database. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional authorities i.e. pandemic, epidemic, or natural disaster, 
that limits or prevents on-site study visits, alternative methods of providing continuing care may be implemented by the investigator as the 
situation dictates. If allowable by a local Health Authority and depending on operational capabilities, phone calls, virtual contacts (e.g. tele 
consult) or visits by site staff/home nursing staff to the participant home, can replace on-site study visits, for the duration of the disruption 
until it is safe for the participant to visit the site again.
Participants may be asked to check‑in to the study site prior to Day 1 to undergo additional COVID‑19 precaution procedures.
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Table 8-1
Assessment Schedule
Period
Screening
Treatment
In-Patient Follow-Up
Outpatient Follow-Up
Visit Name Screening Baseline Treatment
Inpatient Follow-Up
Outpatient Follow-Up 
Visits
Safety Follow-Up 
Call
End 
of 
Study 
Call
Visit Number
1
2
101
102
103 104 105 106 107
108
109
110
111 112 113 114
115
116
117
118
199
Days
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
14
17
21
24
28
35
42
49
56
Informed consent
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Understanding of 
Cryptosporidium 
Infection & 
Transmission 
Quiz
S
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
history/current 
medical 
conditions
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
Examination
S
S
 
 
 
 
 
 
 
 
 
S
 
 
 
 
S
 
 
 
 
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Period
Screening
Treatment
In-Patient Follow-Up
Outpatient Follow-Up
Visit Name Screening Baseline Treatment
Inpatient Follow-Up
Outpatient Follow-Up 
Visits
Safety Follow-Up 
Call
End 
of 
Study 
Call
Visit Number
1
2
101
102
103 104 105 106 107
108
109
110
111 112 113 114
115
116
117
118
199
Days
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
14
17
21
24
28
35
42
49
56
Inclusion / 
Exclusion criteria
S
S
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol Test, 
Drug Screen, and 
Cotinine Test
S
S
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV2 
Screen
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis screen
S
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV screen
S
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid 
stimulating 
hormone
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
T4 (Free)
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy2
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
 
 
 
 
Body Height
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight11
X
X
X3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
 
Vital Signs11
X
X
X3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
 
Electrocardiogram 
(ECG)11
X
X
X3
 
 
 
 
 
 
 
 
X
 
 
 
 
X
 
 
 
 
Hematology11
X
 
X3
 
 
 
 
 
 
 
 
X
 
 
 
 
X
 
 
 
 
Clinical 
Chemistry11
X
 
X3
 
 
 
 
 
 
 
 
X
 
 
 
 
X
 
 
 
 
Urinalysis11
X
X
X3
 
 
 
 
 
 
 
 
X
 
 
 
 
X
 
 
 
 
ABO809 
administration
 
 
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Period
Screening
Treatment
In-Patient Follow-Up
Outpatient Follow-Up
Visit Name Screening Baseline Treatment
Inpatient Follow-Up
Outpatient Follow-Up 
Visits
Safety Follow-Up 
Call
End 
of 
Study 
Call
Visit Number
1
2
101
102
103 104 105 106 107
108
109
110
111 112 113 114
115
116
117
118
199
Days
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
14
17
21
24
28
35
42
49
56
Participants 
domiciled13
 
X 
 
 
 
 
 
 
Stool Collection 12
X
X
X
X
X
X
X
X
X
X
X
X
X4
X4
X4
X4
X4
 
 
 
 
Occult Blood
X
X
 
X
 
X
 
X
 
X
 
X
 
 
 
 
 
 
 
 
 
Cryptosporidium 
Antigen by EIA10, 
12
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
 
IgA
X
Evaluation of 
Clinical Signs and 
Symptoms6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
 
CHIM Diary
 
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
X14
 
 
 
 
Standard of Care 
Drug 
Administration 
(Nitazoxanide)8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
 
 
 
 
 
 
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Period
Screening
Treatment
In-Patient Follow-Up
Outpatient Follow-Up
Visit Name Screening Baseline Treatment
Inpatient Follow-Up
Outpatient Follow-Up 
Visits
Safety Follow-Up 
Call
End 
of 
Study 
Call
Visit Number
1
2
101
102
103 104 105 106 107
108
109
110
111 112 113 114
115
116
117
118
199
Days
-28 to -2
-1
1
2
3
4
5
6
7
8
9
10
14
17
21
24
28
35
42
49
56
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 X
 X
X 
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
X 
 X
X
Safety Follow-Up 
Call for Study 
Participants
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S
S
S
S
Study completion 
information
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
Period
Post-Study Follow-Up
Visit Name
Post-Study Follow-Up Call
Days
6 Month Phone Contact
12 Month Phone Contact
Informed consent
 
 
Understanding of Cryptosporidium Infection 
& Transmission Quiz
 
 
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Period
Post-Study Follow-Up
Visit Name
Post-Study Follow-Up Call
Days
6 Month Phone Contact
12 Month Phone Contact
Medical history/current medical conditions
Physical Examination
Inclusion / Exclusion criteria
Demography
Alcohol Test, Drug Screen, and Cotinine 
Test
SARS-CoV2 Screen
Hepatitis screen
HIV screen
Thyroid stimulating hormone
T4 (Free)
Pregnancy2
Body Height
Body Weight11
Vital Signs11
Electrocardiogram (ECG)11
Hematology11
Clinical Chemistry11
Urinalysis11
ABO809 administration
Participants domiciled13
Stool Collection12
Occult Blood
Cryptosporidium Antigen by EIA10, 12
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Period
Post-Study Follow-Up
Visit Name
Post-Study Follow-Up Call
Days
6 Month Phone Contact
12 Month Phone Contact
IgA
Evaluation of Clinical Signs and Symptoms6
 
 
CHIM Diary
 
 
Standard of Care Drug Administration 
(Nitazoxanide)8
 
 
Concomitant medications
 
 
Adverse Events
S15
S15
Safety Follow-Up Call for Study Participants
S
S
Study completion information
 
 
2 Serum pregnancy tests at Screening and Day 28. Urine pregnancy test at Baseline.
3 Before ABO809 administration. 
4 Participants should make every attempt to bring self-collected stool specimen to the clinic for each Outpatient Follow-Up visit. In the 24 hours prior to each Outpatient 
Follow-Up visit, all stools should be collected.
5 During screening, the first diarrheal stool, and the first diarrheal stool with relapse after clinical clearance will be tested for enteral pathogenic micro-organisms. 
6 Includes number and frequency of diarrheal episodes, stool weight, volume, and grading (see Section 8.3.2, Section 8.4.1, and Appendix 1). Additionally, includes 
evaluation of nausea, vomiting, abdominal pain or discomfort, abdominal tenderness, abdominal rebound, abdominal distension, fecal urgency, diarrhea, flatulence, 
tenesmus, poor appetite, dehydration, fever, and electrolyte imbalance 
8 Nitazoxanide to be administered per Prescribing Information (i.e. 500 mg every 12 hours for 3 days). Nitazoxanide administration will be captured on the standard 
concomitant medication page, and no specific CRF is required.
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Period
Post-Study Follow-Up
Visit Name
Post-Study Follow-Up Call
Days
6 Month Phone Contact
12 Month Phone Contact
11 Additional tests can be done at the discretion of the Investigator e.g., in the case of dehydration.
13 All participants, whether or not they are symptomatic, will be domiciled in a unit until completion of Day 10 assessments. Participants who experience symptoms will 
remain domiciled for the duration of the diarrheal illness up to a maximum of Day 21. If a participant experiences diarrhea after Day 10 (after the participant has been 
discharged from the study site), the participant may be readmitted, at the discretion of the Investigator, to remain domiciled until the cessation of symptoms or Day 
21, whichever is earlier.
14 CHIM diary eCRF page will capture only if the diary was fully complete or not. No data from the diary will be recorded on this diary eCRF page. AEs will be captured 
on the standard AE eCRF, and nitazoxanide administration will be captured on the standard concomitant medication eCRF page. 
15 Adverse events of special interest (AESI) defined in Section 10.1.1.1 will be recorded at the 6 and 12 month Post-Study Follow-up calls as source data and reported to 
Novartis Safety if the Investigator considers there is a reasonable possibility that  ABO809 caused the event, unless otherwise specified by local law/regulations.
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8.1
Screening
It is permissible to re-screen a participant once if s/he fails the initial Screening (see Section 5.1). 
Participants need to re-consented (see Section 7) for re-screening and a new participant number 
must be assigned (see Section 6.3).
In the case where a safety laboratory assessment at Screening and/or Baseline is outside of the 
range specified in the eligibility criteria (see Section 5.2), the assessment may be repeated once. 
If the repeat value remains outside of the specified ranges, the participant must be excluded 
from the study.
8.1.1
Eligibility screening
Results of below screening measurements will be available as source data at the study site and 
will not be recorded within the eCRF unless specified below.
8.1.1.1
Hepatitis screen, HIV screen
All participants will be screened for Hepatitis B surface antigen (HBsAg) and, if standard local 
practice, Hepatitis B core antigen (HBcAg). Screening for Hepatitis C will be based in HCV 
antibodies and if positive, HCV RNA levels should be determined.
Evaluation for HIV seropositivity will be performed, and, if positive, confirmed by a second 
technique available at the laboratory site or a central lab e.g. Western blot. Appropriate 
counseling will be made available by the Investigator in the event of a positive confirmatory 
test. Notification of state and federal authorities, as required by law, will be the responsibility 
of the Investigator.
8.1.1.2
Alcohol test, Drug screen, Urine cotinine
Participants will be tested for evidence of alcohol and substances of abuse (e.g. alcohol, 
amphetamines, barbiturates, benzodiazepines, cannabinoids including tetrahydrocannabinol 
(THC), cocaine and opiates). Each participant will be tested for urine cotinine levels.
8.1.1.3
Understanding of Cryptosporidium Infection & Transmission Quiz
Participants will be educated on facts about Cryptosporidium disease, safety measures and 
transmission risks. They must then score 100% on a quiz assessing their understanding 
of Cryptosporidium infection and transmission. Participants will have the opportunity to retake 
the quiz.
8.1.1.4
SARS CoV-2 Screen
As applicable by local guidelines and regulations, participants will undergo testing of SARS 
CoV-2 infection to be allowed to participate in the study. COVID-19 prevention policies will 
be followed. SARS CoV-2 screen results will be entered into the database.
8.1.2
Information to be collected on screening failures
Participants who sign an Informed Consent form and subsequently found to be ineligible will 
be considered a screen failure. The reason for screen failure should be entered on the applicable 

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Case Report Form. The demographic information, informed consent, and Inclusion/Exclusion 
pages must also be completed for screen failure participants. No other data will be entered into 
the clinical database for participants who are screen failures, unless the participant experienced 
a serious adverse event during the screening phase (see Section 10.1.3).
Participants who sign an Informed Consent and are considered eligible but fail to receive a dose 
of ABO809 for any reason will be considered an early terminator. The reason for early 
termination should be captured on the appropriate disposition Case Report Form.
8.2
Participant demographics/other baseline characteristics
Participant demographics including full date (only if required and permitted) or year of birth or 
age, sex, race/predominant ethnicity (if permitted) and relevant medical history/current medical 
conditions (until date of signature of informed consent) will be recorded in the eCRF. Where 
possible, the diagnosis and not symptoms should be recorded. Participant race/ethnicity data 
are collected and analyzed to identify any differences in the safety and/or efficacy profile of the 
treatment due to these characteristics. In addition, the diversity of the study population will be 
assessed as required by Health Authorities.
All prescription medications, over-the-counter drugs and significant non-drug therapies prior to 
the start of the study must be documented. See Section 6.2.1 (Concomitant Therapy) for further 
details on what information must be recorded on the appropriate page of the eCRF.
8.3
Efficacy
8.3.1
Cryptosporidium Antigen by EIA
To assess the incidence of Cryptosporidium infection, fresh stool samples will be collected at 
Screening and during the study as detailed in the Assessment Schedule (see 
Table 8-1). While participants are domiciled, all stools will be collected for grading and 
quantity record, however, up to 3 stool samples per day, each separated by approximately 4 
hour intervals, will be analyzed by EIA 
 at a CLIA 
laboratory for parasitological assessment of oocyst shedding. If the participant passes less than 
3 stools on any given day during domiciling (1 or 2) then these stool samples will be used for 
parasitological assessment.
8.3.2
Evaluation of Clinical Signs and Symptoms
To assess the incidence and characteristics of cryptosporidiosis, the signs and symptoms 
associated with cryptosporidiosis will be monitored as described in the Assessment Schedule 
(Table 8-1).
Onset, progression, improvement and resolution of signs and symptoms associated 
with Cryptosporidium infection will be recorded in the eCRF at Baseline and approximately 
CCI
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every 8 hours during the Inpatient Follow-Up period, at Outpatient Follow-Up visits/Safety 
Follow-Up Calls and at any unscheduled visits. Symptoms of cryptosporidiosis will be AEs; 
these and any SAEs will be recorded as such (see Section 10).
Diarrhea is defined as at least one stool sample grading 3-5 on the Stool Grading System (see 
Section 16.1) in one day. Grades 3-5 stools are defined as thick liquid diarrhea taking the shape 
of the container, opaque watery, rice water or clear watery stools. Diarrhea will be further 
characterized by measuring the form of the stool, the total weight of stool, the number and 
frequency of diarrheal episodes and the time to resolution of diarrheal illness.
Diarrhea data will be collected as follows: onset, progression, total stool output (weight in 
grams) and severity of diarrhea (Grading will be assessed using the U.S. Food and Drug 
Administration's (FDA) "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007)"; the worst grade each day will be 
recorded).
Data on other gastrointestinal symptoms associated with Cryptosporidium infection will be 
recorded in the eCRF as follows: presence (yes/no), onset, severity (mild, moderate, severe), 
therapeutic intervention (yes/no; if yes what) and progression (ongoing, resolved). These 
gastrointestinal symptoms include: 

abdominal pain or discomfort

abdominal tenderness

abdominal rebound

abdominal distension

fecal urgency

nausea/vomiting

flatulence

tenesmus

poor appetite

presence of blood

fever
Since nausea/vomiting, diarrhea, headache, fatigue, and myalgia are listed in the US FDA 
“Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials (2007)” these symptoms should be graded according to provided 
definitions in the guidance document (compare Section 10.1.1).
Other symptoms the Investigator considers potentially related to ABO809 administration will 
also be recorded in the eCRF as free text.
A participant will be considered as showing clinical diarrheal illness if diarrhea is observed on 
at least two days during the observation period beginning after the ABO809 administration (Day 
1) and ending on Day 28.
Resolution of diarrheal illness from Cryptosporidium infection requires ≥2 consecutive days 
with no diarrheal stools (stool sample grades 1 or 2).

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8.3.2.1
CHIM Diary
Participants will provide a health and stool update daily from Day 1 to Day 28 in a Participant 
CHIM 
Diary. 
 Any 
clinical 
symptoms, 
and/or 
diarrheal 
episodes 
associated 
with Cryptosporidium infection should be recorded. The Diary will be submitted to the site at 
Day 28.
8.3.3
Appropriateness of efficacy assessments
Presence of Cryptosporidium oocysts in the stool following oral administration is well 
established as an indicator of Cryptosporidium infection (DuPont et al 1995). Analysis of stool 
by EIA 
 is considered an appropriate method to detect the 
presence of fecal Cryptosporidium oocysts (see Section 8.3.1).
Systematic measurement and assessment of cryptosporidiosis-associated signs and symptoms 
(see Section 8.3.2) and AEs (see Section 10) are considered appropriate to assure participant 
safety and qualify/quantify the illness expected to be elicited by ABO809 administration.
8.4
Safety
Safety assessments are specified in the Assessment Schedule (see Table 8-1 which details when 
each assessment is to be performed.
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, 
regular phone or virtual calls can occur (every 2 weeks or more frequently if needed) for safety 
monitoring and discussion of the participant´s health status until it is safe for the participant to 
visit the site again.
Table 8-2
Assessments and Specifications
Assessment
Specification
Physical Examination
A complete physical examination at screening 
will include the examination of general 
appearance, skin, neck (including thyroid), eyes, 
ears, nose, throat, lungs, heart, abdomen, back, 
lymph nodes, extremities, vascular, and 
neurological. If indicated based on medical 
history and/or symptoms, rectal, external 
genitalia, breast, and pelvic exams will be 
performed.
At other visits, a shorter physical exam may be 
performed to include the examination of general 
appearance.
Information for all physical examinations must be 
included in the source documentation at the 
study site. Clinically relevant findings that are 
present prior to signing informed consent must 
be included in the Medical History part of the 
eCRF. Significant findings made after signing 
informed consent which meet the definition of an 
Adverse Event must be recorded on the Adverse 
Event section of the eCRF.
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Assessment
Specification
Vital Signs
Vital signs will include the collection of body 
temperature (recorded in °C), blood pressure 
(BP) and pulse measurements.
After the participant has been sitting for 3 
minutes, with back supported and both feet 
placed on the floor, systolic and diastolic BP will 
be measured using an automated validated 
arm device, e.g. OMRON with an appropriately 
sized cuff. In case the cuff sizes available are 
not large enough for the participant's arm 
circumference, a sphygmomanometer with an 
appropriately sized cuff may be used.
If vital signs are out-of-range at screening and/or 
baseline (see Inclusion Criteria Section 5.1 of 
the protocol for details), two additional readings 
can be obtained, so that up to three consecutive 
assessments are made, with the participant 
seated quietly for approximately five minutes 
preceding each repeat assessment. The last 
reading must be within the ranges provided in 
the eligibility criteria in order for the participant to 
qualify.
In case of repeated vital assessments, the eCRF 
should contain all repeat measurements
Height and weight
Height in centimeters (cm) and body weight (to 
the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured.
Body mass index (BMI) will be calculated using 
the following formula:
· BMI = Body weight (kg) / [Height (m)]2
The Screening Visit height measurement will be 
used for BMI calculations throughout the study.
Additional laboratory assessments, vital signs assessments, physical exams, ECGs and other 
safety measures can be conducted any time when indicated in the opinion of the investigator 
(e.g. in case of diarrheal illness with substantial loss of fluid volume, orthostatic dysregulation, 
fever).
For details on AE collection and reporting, refer to Section 10.1.
8.4.1
Laboratory evaluations
Clinically significant abnormalities must be recorded either as medical history/current medical 
conditions or adverse events as appropriate.
In the case where a laboratory range is not specified by the protocol, but a value is outside the 
reference range for the laboratory at screening and/or initial baseline, a decision regarding 
whether the result is of clinical significance shall be made by the Investigator in consultation 
with the Sponsor. The decision shall be based upon the nature and degree of the observed 
abnormality. The assessment may be repeated at Screening.

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In all cases, the Investigator must document in the source documents, the clinical considerations 
(i.e., result was/was not clinically significant and/or medically relevant) in allowing or 
disallowing the participant to continue in the study.
A local laboratory will be used for analysis of all safety specimens collected. Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
to Investigators in the central laboratory manual.
Urinalysis
A midstream urine sample (approx. 30 mL) will be obtained, in order to avoid contamination 
with epithelial cells and sediments, and allow proper assessments.
Special clinical laboratory evaluations
Refer to Section 8.3.2
Table 8-3
Laboratory Assessments
Test Category
Test Name
Hematology
Hemoglobin, hematocrit, red blood cell (RBC) 
count, white blood cell (WBC) count with 
differentials and platelet count. Coagulation 
testing including prothrombin time (PT) (also 
reported as INR) and activated partial 
thromboplastin time (aPTT)
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Test Category
Test Name
Chemistry
Sodium, potassium, creatinine, BUN or urea, 
uric acid, chloride, albumin, calcium, 
magnesium, alkaline phosphatase, total bilirubin 
(direct and indirect), bicarbonate/HCO3, LDH, 
GGT, AST, ALT, amylase, lipase, CK, glucose, 
total cholesterol, triglycerides and total protein
Urinalysis
Dipstick measurements for bilirubin, blood, 
glucose, ketones, leukocytes, nitrite, pH, protein, 
specific gravity, urobilinogen will be performed. If 
dipstick measurement results are positive 
(abnormal),then microscopy must be assessed 
with results loaded into the database.
Microscopic Panel (Red Blood Cells, White 
Blood Cells, Casts, Crystals, Bacteria, Epithelial 
cells)
Macroscopic Panel (Dipstick) (Color, Bilirubin, 
Blood, Glucose, Ketones, Leukocytes esterase, 
Nitrite, pH, Protein, Specific Gravity, 
Urobilinogen)
Thyroid
T4 [free], TSH
Screening Tests
Hepatitis (HBV-DNA, HBsAg, HBsAb, HBcAb, 
HCV RNA-PCR), HIV screen, alcohol test, drug 
screen, urine cotinine
Pregnancy Test
Serum / Urine pregnancy test
8.4.2
Electrocardiogram (ECG)
All ECGs will be measured after a 10 minute rest in the supine position. The following 
parameters will be reported: PR interval, QRS duration, heart rate, RR interval, QT interval and 
QTcF interval.
The Fridericia QT correction formula (QTcF) must be used for clinical decisions: QTcF = 
QT/(RR/1s)1/3 
 As applicable, QTcF and QTcB may be calculated at the site. Unless auto-calculated by the 
ECG machine, the Investigator must calculate QTcF at the Screening and/or Baseline visit(s) 
(as applicable) to assess eligibility and continuation in the study.
Additional, unscheduled, safety ECGs may be repeated at the discretion of the investigator at 
any time during the study as clinically indicated, e.g. in the case of dehydration.
For any ECGs with participant safety concerns, two additional ECGs must be performed to 
confirm the safety finding. ECG safety monitoring, or a review process, should be in place for 
clinically significant ECG findings at baseline before administration of study treatment and 
during the study.
Clinically significant abnormalities must be recorded on the eCRF as either medical 
history/current medical condition or adverse event as appropriate.

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8.4.3
Pregnancy
All pre-menopausal women who are not surgically sterile will be tested for pregnancy at 
Screening, Baseline and the Day 28 visit. Additional pregnancy testing might be performed if 
requested by local requirements.
At Screening and on Day 28, a serum pregnancy test will be performed. A urine pregnancy test 
will be performed at Baseline. During the study duration, urinary pregnancy tests are sufficient. 
In case the pregnancy urine test is positive, the result needs to be confirmed with serum test. 
Pregnancy testing information will be captured in the database.
8.4.4
Appropriateness of safety measurements
The safety assessments selected cover all standard assessments for studies in healthy 
participants. In addition, the assessments address the potential health impact of a C. parvum 
oocyst administration, which is expected to results in diarrhea and other mainly gastrointestinal 
symptoms as well as potential changes in water and electrolyte balance.
8.5
Additional assessments
Additional assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed.
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9
Study discontinuation and completion
9.1
Discontinuation and completion
This is a single dose study, therefore discontinuation of study treatment is not applicable.
9.1.1
Study treatment discontinuation and study discontinuation
Discontinuation from study treatment is when the participant permanently stops receiving 
ABO809 and further protocol-required assessments or follow-up for any reason.
If a participant agrees to a final evaluation at the time of the participant's discontinuation, the 
evaluation should be performed as detailed in the assessment schedule (see Section 8).
Stopping the study for an individual participant can be initiated by either the participant or the 
Investigator. There is no discontinuation of ABO809 administration since this is a single dose 
study. The Investigator must discontinue the study for a given participant if he/she believes that 
continuation would negatively impact the participant's safety.
The study must be discontinued for an individual participant under the following circumstances:

Participant decision

The Investigator believes that continuation would negatively impact the safety of the 
participant or the risk/benefit ratio of study participation

Any other protocol deviation that results in a significant risk to the participant’s safety 
prior to dosing

Any confirmed COVID -19 case that warrants discontinuation of the study for the 
participant in the judgment of the Investigator or Sponsor to protect the safety of the 
participant, other study participants or study site staff 
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Participants who discontinue the study or who decide they do not wish to participate in the study 
further should NOT be considered withdrawn from the study UNLESS they withdraw their 
consent (see Section 9.1.2). Where possible, they should return for the assessments as indicated 
in the Assessment Schedule (see Table 8-1).
Participants who discontinue from the study after ABO809 administration will be treated with 
nitazoxanide as described in Section 4.1.
If participants fail to return for these assessments for unknown reasons, every effort (e.g., 
telephone, e‑mail, letter) should be made to contact the participant as specified in the Lost to 
follow‑up section (see Section 9.1.3).
After a participant discontinues the study, the following data should be collected at clinic visits 
or via telephone/email contact if possible:

New / concomitant treatments

AEs / SAEs
Participants meeting study discontinuation and stopping criteria will continue to be monitored 
for safety if possible and will be included in the safety analyses.
9.1.1.1
Replacement policy
Participants will not be replaced on this study. Should fewer than 10 participants be evaluable 
in a given cohort, the number of participants may be increased in subsequent cohorts. A total of 
up to 6 sequential cohorts may be enrolled (see Section 4 and Section 6.5).
9.1.2
Withdrawal of informed consent
Withdrawal of consent/opposition to use data/biological samples occurs when a participant:

Explicitly requests to stop use of their biological samples and/or data (opposition to use 
participant’s data and biological samples)
and

No longer wishes to receive study treatment
and

Does not want any further visits or assessments (including further study-related contacts)
The Investigator should make a reasonable effort (e.g. telephone, e-mail, letter) to understand 
the primary reason for the participant’s decision to withdraw their consent/opposition to use 
data/biological samples and record this information.
Where consent to the use of Personal and Coded Data is not required in a certain country's legal 
framework, the participant therefore cannot withdraw consent. However, they still retain the 
right to object to the further collection or use of their Personal Data.
ABO809 administration must be discontinued and no further assessments conducted, and the 
data that would have been collected at subsequent visits will be considered missing.
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up.

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If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/opposition to use data/biological samples should be made as detailed in the assessment 
table (refer to Section 8).
Novartis will continue to retain and use all research results (data) that have already been 
collected for the study evaluation, including processing of biological samples that has already 
started at time of consent withdrawal/opposition. No new Personal Data (including biological 
samples) will be collected following withdrawal of consent/opposition.
9.1.3
Lost to follow-up
If the participant cannot or is unwilling to attend any Outpatient Follow-Up visit(s), the site 
staff should maintain regular telephone contact with the participant if possible. This telephone 
contact should preferably be done according to the Schedule of Assessments.
For participants whose status is unclear because they fail to appear for Outpatient Follow-Up 
visits and/or 6 and 12 month Safety Follow-Up Calls without stating an intention to discontinue 
or withdraw, the Investigator must show "due diligence" by documenting in the source 
documents steps taken to contact the participant, e.g. dates of telephone calls, registered letters, 
etc. A participant should not be considered as lost to follow-up until due diligence has been 
completed or until the end of the study.
9.1.4
Study stopping rules
Dosing of ABO809 will be done approximately simultaneously by cohort. The temporal spacing 
between one cohort and the next is anticipated to be approximately 21 days. Dosing of 
additional participants may be stopped due to safety concerns. Participants who have already 
been dosed with ABO809 at the time safety concerns become apparent will continue in the 
study until the Day 56 visit is completed (see Section 3 and Section 4).
Dosing in this study may be placed on hold if safety concerns are observed, and a safety review 
will be conducted within approximately 48 hours. No further dosing will take place until this 
safety review is completed.
Criteria leading to a decision to not dose additional participants are:  

One or more ABO809 related-SAEs, such as signs and symptoms of extra-intestinal 
cryptosporidiosis or complications.

At least 2 of the participants in the same cohort experience a similar AE which is assessed 
as severe in intensity, and is potentially related to study treatment (illness consistent with 
gastrointestinal cryptosporidiosis which is expected and desired in the context of this 
study is not in scope for this criterion)

The Sponsor considers that the number and/or severity of AEs, abnormal safety 
monitoring tests or abnormal laboratory findings justify putting the study on hold
Should a decision be made to not dose additional participants, already dosed participants will 
continue to be monitored for safety and included in the safety analysis (Safety Follow-Up Calls 
will be conducted).
Dosing of the next cohort / additional participants may resume following the safety review, if 
the Investigator and Sponsor agree it is safe to proceed (also see Section 8.4).

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9.1.5
Early study termination by the sponsor
The study can be terminated by Novartis at any time. Potential reasons for early termination 
may include but are not limited to:

Unexpected, significant, or unacceptable safety risk to participants enrolled in the study

Discontinuation of ABO809 clinical supply
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a participant who discontinued from dosing of ABO809 (see Section 9.1.4). The Investigator 
may be informed of additional procedures to be followed in order to ensure that adequate 
consideration is given to the protection of the participant’s interests. The Investigator or Sponsor, 
depending on the local regulations, will be responsible for informing IRBs/IECs of the early 
termination of the study.
9.2
Study completion and post-study treatment
Study completion is defined as when the last subject finishes their EOS visit, and any repeat 
assessments associated with this visit have been documented and followed-up appropriately by 
the Investigator, or in the event of an early study termination decision, the date of that decision.
Each participant will be required to complete the study in its entirety.
All participants who received ABO809 should have a safety follow-up call conducted 
approximately 60 days after administration of ABO809. All AEs reported during this time 
period must be reported as described in Section 10.1.3.
Post-study Follow-Up calls scheduled after the EOS visit will be conducted at 6 and 12 months 
after the Day 1 visit to collect adverse event of special interest (AESI) information.
Documentation of attempts to contact the participant should be recorded in the source 
documentation.

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10
Safety monitoring and reporting
As part of a CHIM study, AEs associated with Cryptosporidium infection are expected.
AEs and SAEs will be monitored, treated and appropriately recorded by the Investigator from 
Day 1 until EOS (Day 56). AESI information will be collected at the 6 month and 12 month 
Post-Study Follow-Up Phone Calls.
10.1
Definition of adverse events and reporting requirements
10.1.1
Adverse events
An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease in a participant after providing written informed 
consent for participation in the study. An AE is temporally associated with the use of a medical 
treatment or procedure and may or may not be considered related to the medical treatment or 
procedure.
The Investigator has the responsibility for managing the safety of individual participants and 
identifying adverse events. Expected symptoms following Cryptosporidium infection are 
described in Section 8.3.2 and in the Investigator’s Brochure (IB).
All clinical signs and symptoms associated with Cryptosporidium infection will be 
characterized as AEs and entered in the eCRF. The AE should be described using the diagnosis 
"Gastrointestinal Cryptosporidiosis," rather than listing individual underlying signs and 
symptoms.
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems.
Recording and Grading of AEs
Adverse events may be detected through physical examination findings, laboratory test findings, 
or other assessments made by site personnel or when they are volunteered by the participant 
during or between visits. Information on adverse events must be obtained by non-directive 
questioning of the participant.
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than only individual underlying signs and 
symptoms.
All AEs must be recorded and accompanied by the following information (as far as possible):
1. The AE severity grade:
Grading will be assessed using the U.S. Food and Drug Administration's (FDA) "Toxicity 
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials (2007)". For AE reporting based on laboratory values, local laboratory normal 
ranges may be used at the discretion of the Investigator, and if so, must be used consistently 
throughout the study. These may differ from the normal ranges given in the FDA grading scale. 
In case of such discrepancies, the Investigator will take into consideration the FDA 

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recommendations as to the magnitude of deviations from normal provided in the FDA grading 
scale.
For AEs that are not contained in the "Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007)", the following categorization 
will be used:

Mild: usually transient in nature and generally not interfering with normal activities

Moderate: sufficiently discomforting to interfere with normal activities

Severe: prevents normal activities
2. The AE relationship (causality) to the study treatment will be assessed for all AEs recorded 
during treatment and follow-up by the investigator. The criteria for assessing the AE 
relationship to the study treatment are listed below:
a.
Related – There is reasonable possibility that the study treatment caused the AE. 
Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study treatment and the AE.
b. Not related – There is no reasonable possibility that the administration of the 
study treatment caused the event.
3. The AE duration (start and end dates) or if the event is ongoing, an outcome of not 
recovered/not resolved must be reported
4. Whether the AE constitutes an SAE (see Section 10.1.2 for the SAE definition)
5.  Its outcome (i.e. recovery status or whether it was fatal)
AEs Follow-up
All adverse events must be treated appropriately. Conditions that were already present at the 
time of informed consent should be recorded in medical history of the participant.
Once an adverse event is detected, assessment must be made at each visit (or more frequently, 
if necessary) of any changes in severity, the suspected relationship to the interventions required 
to treat it, and the outcome. AEs must be followed, in person or by phone call as appropriate, 
until resolution or until judged to be permanent (i.e. unresolved at the EOS).
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:

they induce clinical signs or symptoms

they are considered clinically significant

they require therapy
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in participants 
with the underlying disease.

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10.1.1.1 Adverse events of special interest
All participants may report adverse events associated with Cryptosporidium infection as 
detailed in Section 4.5 Risks and benefits.  The Investigator will report AESI and follow-up 
accordingly; these include:

Gastroenteritis in the absence of Cryptosporidium infection: In the event of 
gastroenteritis in the absence of Cryptosporidium infection, the event will be considered 
an AESI. The Investigator will investigate other potential causes of diarrhea, including 
infectious diarrhea and manage participant's care according to local standards.

Extraintestinal cryptosporidiosis: Cryptosporidium infection involving the biliary tract, 
lungs, liver, pancreas, or other organs will be considered AESI (also see Section 4.5 Risks 
and benefits).

Persistent or recurrent cryptosporidiosis: Persistent clinical symptoms after 
administration of standard of care, or after initial resolution of Cryptosporidium oocysts in 
the stool and/or diarrheal symptoms, will be considered an AESI.

Persistent Cryptosporidium shedding: Persistent detection of Cryptosporidium oocysts in 
stools after treatment with nitazoxanide will be considered an AESI. Participants with 
persistent shedding may be treated with combination therapy as detailed in Section 6.2.3.

Dehydration: Moderate or severe dehydration, as defined below will be considered an 
AESI. 

Mild: dry mucous membranes; diminished skin turgor; increased oral fluids are 
indicated

Moderate: IV fluids are indicated

Severe: hospitalization is indicated or it is considered to have life-threatening 
consequences; or an urgent intervention is indicated

Non-intestinal sequelae: Development of new onset non-intestinal symptoms, including 
eye pain or joint pain, will be considered AESI.
If any AESIs are experienced after EOS (i.e. Post-Study Safety Follow-up calls at 6 and 12 
months) in which the Investigator considers there is a reasonable possibility that ABO809 
caused the event, the event will be recorded and reported following the same procedure as SAEs 
as described in Section 10.1.3. These AESIs will be captured in the Novartis safety database, 
included in an addendum to the CSR and reported to the competent authorities and relevant 
ethics committees as per national regulatory requirements in participating countries. 
10.1.2
Serious adverse events
An SAE is defined as any adverse event [appearance of or worsening of any pre-existing] 
undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the following 
criteria:

Fatal

Life-threatening
A life-threatening SAE refers to a reaction in which the participant was at risk of death at the 
time of the reaction; it does not refer to a reaction that hypothetically might have caused death 

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if it were more severe (please refer to the ICH E2D (2004) Clinical Safety Data Management: 
Definitions and Standards for expedited reporting).

Results in persistent or significant disability/incapacity

Constitutes a congenital anomaly/birth defect

Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 

Social reasons and respite care in the absence of any deterioration in the participant’s 
general condition

Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission

Is medically significant, i.e. defined as an event that jeopardizes the participant or 
may require medical or surgical intervention to prevent one of the outcomes listed 
above
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant”. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions that do 
not result in hospitalization or development of dependency or abuse (please refer to the 
ICH E2D (2004) Clinical Safety Data Management: Definitions and Standards for expedited r
eporting).
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All reports of intentional misuse and abuse of ABO809 are also considered serious adverse 
event irrespective if a clinical event has occurred.
10.1.3
SAE reporting
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until EOS (Day 56) must be reported to Novartis Safety 
immediately, without undue delay, under no circumstances later than within 24 hours of 
learning of its occurrence. Detailed instructions regarding the submission process and 
requirements are to be found in the Investigator folder provided to the study site. Information 
about all AEs is collected and recorded on the Serious Adverse Event Report Form: all 
applicable sections of the form must be completed in order to provide a clinically thorough 
report.
SAEs occurring after the participant has provided informed consent until the time the participant 
is deemed a Screen Failure must be reported to Novartis.
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 

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within 24 hours of the Investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event.
If the SAE is not previously documented in the Investigator’s Brochure and is thought to be 
related to ABO809, a CMO & PS Department associate may urgently require further 
information from the Investigator for health authority reporting. Novartis may need to issue an 
Investigator Notification (IN) to inform all Investigators involved in any study with ABO809 
that this SAE has been reported.
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees as per national regulatory 
requirements in participating countries.
If any SAEs are experienced after EOS (i.e. Post-Study Safety Follow-up calls at 6 and 12 
months) in which the Investigator considers there is a reasonable possibility thatABO809 
caused the event, the event should be recorded, reported, and captured in the Novartis safety 
database. All such SAEs will be included in an addendum to the CSR and reported to the 
competent authorities and relevant ethics committees as per national regulatory requirements in 
participating countries.
10.1.4
Pregnancy reporting
Pregnancies
Women of child-bearing potential, defined as all women physiologically capable of becoming 
pregnant, are excluded from study unless they are using highly effective methods of 
contraception while in the study (see Section 5.2). Therefore, pregnancies are not expected 
during the study.
However, if a female trial participant becomes pregnant, ABO809 must not be administered (if 
detected before dosing), and the pregnancy consent form should be presented to the trial 
participant. The participant must be given adequate time to read, review, and sign the pregnancy 
consent form. This consent form is necessary to allow the Investigator to collect and report 
information regarding the pregnancy. To ensure participant safety, each pregnancy occurring 
after signing the informed consent must be reported to Novartis within 24 hours of learning of 
its occurrence. If the pregnancy is detected between Day 1 and EOS the pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications.
Pregnancy should be recorded and reported by the Investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported.
Pregnancy outcomes should also be collected for the female partners of any males who received 
ABO809 in this study if the calculated day of conception is between Day 1 and EOS. Consent 
to report information regarding these pregnancy outcomes should be obtained from the mother.

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The newborn conceived between Day1 and EOS will be followed up for a minimum of 1 year 
after delivery.
10.1.5
Reporting of study treatment errors including misuse/abuse
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition).
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects.
Nitazoxanide errors and uses outside of what is foreseen in the protocol will be recorded on the 
appropriate eCRF irrespective of whether or not associated with an AE/SAE and reported to 
Novartis Safety only if associated with an SAE. Misuse or abuse will be collected and reported 
in the safety database irrespective of being associated with an AE/SAE within 24 hours of 
Investigator’s awareness.
Table 10-1
Guidance for capturing the nitazoxanide errors including 
misuse/abuse
Treatment error type
Document in Dosing 
eCRF (Yes/No)
Document in AE 
eCRF
Complete SAE form
Unintentional 
nitazoxanide error
Yes
Only if associated with 
an AE
Only if associated with 
an SAE
Misuse/Abuse
Yes
Yes
Yes, even if not 
associated with a SAE
For more information on AE and SAE definition and reporting requirements, please 
see Section 10.1.1 and Section 10.1.2.
10.2
Additional Safety Monitoring
Not applicable
11
Data Collection and Database management
11.1
Data collection
The Investigator or designated staff will enter the data required by the protocol into the 
Electronic Case Report Forms (eCRF). The eCRFs have been built using fully validated secure 
web-enabled software that conforms to 21 CFR Part 11 requirements; the Investigator and site 
staff will not be given access to the EDC system until they have been trained. Automatic 
validation programs check for data discrepancies in the eCRFs, allow modification and/or 
verification of the entered data by the investigator or designated staff.
The Investigator/designee is responsible for assuring that the data (recorded on eCRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate.

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Certain data may be captured via other source documentation (such as safety laboratory data 
report) and then transcribed, uploaded or transferred into the system. This, and any additional 
data treated in this manner, will be source data verified by the Novartis study monitor per the 
monitoring plan and the location of source data (i.e., source, paper or a local electronic system) 
will be documented prior to study start in the Data Quality Plan. The system has the ability to 
illustrate when a document has been entered from another source. When using an electronic 
source record as the original point of data capture, there is no additional data entry step for the 
site for data collected directly into the application; rather, the electronic source record directly 
populates the study database. Automatic validation programs check for data discrepancies and, 
by generating appropriate error messages, allow the data to be confirmed or corrected before 
transfer of the data to Sponsor. Remote monitoring of the original electronic source records will 
take place, however on-site monitoring inspections will continue to take place in order to review 
data entry of source documentation directly captured on paper and transcribed into the system, 
to ensure protocol adherence, to assess site operational capabilities, and to perform other 
monitoring activities that cannot be performed remotely.
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site.
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification.
11.2
Database management and quality control
Novartis personnel (or designated CRO) will review the data entered by investigational site 
staff for completeness and accuracy. Electronic data queries stating the nature of the problem 
and requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the EDC system. The Investigator or designated site staff are required to 
respond promptly to queries and to make any necessary changes to the data.
Concomitant treatments and prior medications entered into the database will be coded using the 
WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical classification 
system. Medical history/current medical conditions and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology.
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and made available for data analysis. Any changes to 
the database after that time can only be made after written agreement by Novartis development 
management.
11.3
Site monitoring
Before study initiation, at a site initiation visit or at an Investigator’s meeting, a Novartis or 
delegated CRO representative will review the protocol and data capture requirements (i.e. 
eSource or eCRFs) with the Investigators and their staff. During the study, Novartis employs 
several methods of ensuring protocol and GCP compliance and the quality/integrity of the site’s 
data. The Novartis field monitor will visit the site to check the completeness of participant 
records, the accuracy of data capture / data entry, the adherence to the protocol and to Good 
Clinical Practice, the progress of enrollment, and to ensure that study treatment is being stored, 

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dispensed, and accounted for according to specifications. Key study personnel must be available 
to assist the field monitor during these visits. Continuous remote monitoring of the site’s data 
may be performed by a centralized Novartis/delegated CRO/CRA organization. Additionally, 
a central analytics organization may analyze data & identify risks & trends for site operational 
parameters, and provide reports to Novartis clinical teams to assist with trial oversight.
The Investigator must maintain source documents for each participant in the study, consisting 
of case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
subject’s file. The Investigator must also keep the original informed consent form signed by the 
participant (a signed copy is given to the participant).
The Investigator must give the Novartis monitor access to all relevant source documents to 
confirm their consistency with the data capture and/or data entry. Novartis monitoring standards 
require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for all 
primary and secondary objectives. Additional checks of the consistency of the source data with 
the eCRFs are performed according to the study-specific monitoring plan. No information in 
source documents about the identity of the participants will be disclosed,
12
Data analysis and statistical methods
The statistical analysis of this study will be performed by Novartis or a designated CRO. Any 
data analysis carried out independently by the Investigator should be submitted to Novartis 
before publication or presentation. Procedures for data analysis will be further specified in the 
Statistical Analysis Plan (SAP). A Clinical Study Report (CSR) will be prepared following the 
Day 56 visit.
12.1
Analysis sets
For all analysis sets, participants will be analyzed according to the dose of ABO809 (C. parvum 
oocysts, also referred to as “treatment”).
The safety analysis set will include all participants that received ABO809.
The PD analysis set includes all participants with available safety, parasitological and clinical 
data and with no protocol deviations with relevant impact on PD data.
12.2
Participant demographics and other baseline characteristics
Demographic and other baseline data will be listed and summarized descriptively by treatment 
for all participants. Categorical data will be presented as frequencies and percentages. For 
continuous data, mean, standard deviation, median, minimum, and maximum will be presented. 
All demographic data and data on other baseline characteristics (e.g., alcohol, HIV and hepatitis 
screening etc.) will be listed by treatment and participant in detail. Relevant medical history, 
current medical conditions, results of laboratory screens, and any other relevant information 
will be listed by treatment and participant.

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12.3
Treatments
Dose administration will be listed by treatment arm, date and time.
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed and summarized according to the Anatomical Therapeutic 
Chemical (ATC) classification system by treatment.
12.4
Analysis of the primary endpoint(s)/estimand(s)
The primary endpoint is Cryptosporidium infection (detection of oocysts in fecal samples by 
EIA 
 at ≥72 hours post-administration or sooner if associated 
with symptoms suggestive of diarrheal illness) up to Day 10 (inclusive). The 10 day observation 
window may be extended as described in Section 4.1.
12.4.1
Statistical model, hypothesis, and method of analysis
The number and proportion (in percentage) of participants with Cryptosporidium infection will 
be summarized. The lower limit of the 1-sided 80% exact confidence interval of the proportions 
will also be reported.
12.4.2
Supplementary analysis
Not applicable.
12.5
Analysis of secondary endpoints/estimands
The secondary endpoints include the presence of clinical symptoms (diarrheal and associated 
symptoms) by Day 10 and Day 28 as described in Section 8.3.2, Cryptosporidium infection up 
to Day 28, time to infection and symptom on-set, time to resolution of infection and diarrheal 
illness, and characteristics of clinical signs and symptoms associated with diarrheal illness, as 
well as safety and tolerability endpoints.
12.5.1
Efficacy and/or Pharmacodynamic endpoint(s)
The number and proportion (in percentage) of participants with clinical symptoms (by Day 10 
(inclusive) and Day 28) and with Cryptosporidium infection up to Day 28 will be summarized 
by treatment. The lower limit of the 1-sided 80% exact confidence interval of the proportions 
will be reported by treatment. The clinical symptoms are defined as diarrheal and associated 
gastrointestinal symptoms, evaluated from symptom onset up to Day 10. The observation 
window for clinical symptoms may be extended as described in Section 4.1. 
Frequency and percentage will be presented for categorical data such as grading of stool 
consistency and number of diarrhea episodes. Mean, standard deviation, median, minimum, and 
maximum will be presented for continuous data such as stool weight. On-set, duration, time to 
resolution of infection and diarrheal illness as well as severity of other clinical signs and 
symptoms associated with diarrheal illness (including but not limited to abdominal pain, 
abdominal cramping, nausea, vomiting, fever, electrolyte imbalance, dehydration) will be 
analyzed as appropriate. Details will be documented in the Statistical Analysis Plan.
CCI

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12.5.2
Safety endpoints
For all safety analyses, the safety set will be used. All listings and tables will be presented by 
treatment group.
Safety summaries (tables, figures) include data from Day 1 until the EOS with the exception of 
Baseline data which will also be summarized where appropriate (e.g. change from baseline 
summaries). In addition, a separate summary for death including on-treatment and post 
treatment deaths will be provided.
Adverse events
The number (and percentage) of participants with adverse events will be summarized in the 
following ways:

by Primary system organ class and preferred term

by Primary system organ class and preferred term and maximum severity
Separate summaries will be provided for ABO809 related AEs, SAEs, AESIs and deaths.
A participant with multiple AEs within a primary system organ class is only counted once 
towards the total of the primary system organ class.
Vital signs
All vital signs data will be listed by treatment group, participant, and visit/time and if ranges 
are available, abnormalities (and relevant orthostatic changes) will be flagged. Summary 
statistics will be provided by treatment and visit/time.
ECG findings
For ECG parameters, summary statistics for baseline value, actual assessment values, and 
change from baseline values will be presented by time of measurement. All ECG data will be 
listed; notably abnormal values will be flagged, and the overall interpretation of abnormality 
will be presented.
Clinical laboratory evaluations 
Clinical laboratory data will include chemistry, hematology and urinalysis results up to EOS. 
All laboratory values will be converted into International System of Units (SI) units. If grades 
are not defined by the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007), results will be graded by the 
low/normal/high classifications based on laboratory normal ranges. Continuous laboratory data 
will be summarized by presenting summary statistics of raw data and change from baseline 
values (means, medians, standard deviations, ranges) by time point.

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12.6
Analysis of exploratory endpoints
12.7
Interim analyses
Commercially Confidential Information
Commercially Confidential Information

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12.8
Sample size calculation
12.8.1
Primary endpoint(s)
Approximately 10 participants in each cohort will be enrolled to receive ABO809. The sample 
size is driven by practical reasons. Assuming the true incidence of infection is 90%, there is at 
least 80% chance to claim that the incidence is at least 78% with a sample size of 30 participants, 
and 74% with a sample size of 20 participants, and 81% with a sample size of 60 participants. 
The calculation is based on the 1-sided 80% exact confidence interval.
12.8.2
Secondary endpoint(s)
Assuming the true incidence of clinical symptoms is 70%, there is at least 80% chance to claim 
that the incidence is at least 53% with a sample size of 30 participants, and 48% with a sample 
size of 20 participants, and 58% with a sample size of 60 participants. The calculation is based 
on the 1-sided 80% exact confidence interval. 
13
Ethical considerations and administrative procedures
13.1
Regulatory and ethical compliance
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki.
13.2
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the Investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, participant recruitment procedures (e.g., 
advertisements) and any other written information to be provided to participants. Prior to study 
start, the Investigator is required to sign a protocol signature page confirming his/her agreement 
to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol and to give access to all relevant data and records to Novartis 
monitors, auditors, Novartis Quality Assurance representatives, designated agents of Novartis, 
IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site is 
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requested by a regulatory authority, the Investigator must inform Novartis immediately that this 
request has been made.
13.3
Publication of study protocol and results
This study only involves healthy volunteers and as such Novartis will register the protocol as 
required to databases specified by local regulations (e.g. clinicaltrials.gov during CTA filing). 
After study completion and finalization of the study report, results of this trial may be submitted 
for publication (e.g. peer-reviewed journal) or registered to databases where required by local 
regulations.
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials provided at the site initiation visit.
13.4
Quality Control and Quality Assurance
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines.
Audits of Investigator sites, vendors, and Novartis systems are performed by auditors 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach.
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis processes.
14
Protocol adherence
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving ABO809 under the protocol, other than the 
purpose of the study. If despite this interdiction prohibition, data, information, observation 
would be incidentally collected, the Investigator shall immediately disclose it to Novartis and 
not use it for any purpose other than the study, except for the appropriate monitoring on study 
participants.
Investigators will apply due diligence to avoid protocol deviations. If an investigator feels a 
protocol deviation would improve the conduct of the study this must be considered a protocol 
amendment, and unless such an amendment is agreed upon by Novartis and approved by the 
IRB/IEC and Health Authorities, where required, it cannot be implemented.
14.1
Protocol amendments
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation.

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Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified.
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations.

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15
References
References are available upon request
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Chappell CL, Okhuysen PC, Langer-Curry R (2015) Cryptosporidium muris: infectivity and 
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in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G. Am J Trop Med 
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Guerrant RL, DeBoer MD, Moore SR, et al (2013) The impoverished gut--a triple burden of 
diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol p. 220-9.
Hunter PR, Hughes S, Woodhouse S, et al (2004a) Health sequelae of human 
cryptosporidiosis in immunocompetent patients. Clin Infect Dis p. 504-10.
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reporting. Accessed from: 
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00002807.pdf Accessed on: 02Dec2016.
Igloi Z, Mughini-Gras L, Lochlainn L (2018) Long-term sequelae of sporadic 
cryptosporidiosis: a follow-up study. Eur J Clin Microbiol Infect Dis. 2018;37(7):1377-1384
Insulander M, Silverlas C, Lebbad M (2013) Molecular epidemiology and clinical 
manifestations of human cryptosporidiosis in Sweden.2013;141:1009-1020
Kotloff KL, Nataro JP, Blackwelder WC, et al (2013) Burden and aetiology of diarrhoeal 
disease in infants and young children in developing countries (the Global Enteric Multicenter 
Study, GEMS): a prospective, case-control study. Lancet p. 209-22.
Levine MM, Kaper JB, Herrington D, et al (1988) Safety, immunogenicity, and efficacy of 
recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet p. 467-70.
Lopez-Velez R, Tarazona R, Garcia Camacho A (1995) Intestinal and extraintestinal 
cryptosporidiosis in AIDS patients. Eur J Clin Microbiol Infect Dis. 1995; 14(8):677-81
Mac Kenzie WR, Hoxie NJ, Proctor ME, et al (1994) A massive outbreak in Milwaukee of 
cryptosporidium infection transmitted through the public water supply. N Engl J Med; 
331(3):161-167
MacKenzie WR, Kazmierczak JJ, Davis JP (1995) An outbreak of cryptosporidiosis 
associated with a resort swimming pool. Epidemiol Infect p. 545-53.
Okhuysen PC, Chappell CL, Sterling CR, et al (1998a) Susceptibility and serologic response 
of healthy adults to reinfection with Cryptosporidium parvum. Infect Immun 66:441-443.
Okhuysen PC, Chappell CL, Crabb J, et al (1998b). Prophylactic effect of bovine anti- 
Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged 
with Cryptosporidium parvum. Clin Infect Dis 26:1324-1329.
Okhuysen PC, Chappell CL, Crabb JH, et al (1999) Virulence of three distinct 
Cryptosporidium parvum isolates for healthy adults. J Infect Dis p. 1275-81.
Ozgül A, Tanyüksel M, Yazicioglu K, et al (1999) Sacroiliitis associated with 
Cryptosporidium parvum in an HLA-B27-negative patient. Rheumatology (Oxford) p. 288-9.
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Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents (2018). Guidelines 
for the prevention and treatment of opportunistic infections in HIV-infected adults and 
adolescents: recommendations from the Centers for Disease Control and Prevention, the 
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protozoan pathogen cryptosporidium. Interdiscip Perspect Infect Dis. 2010:1-39
Rehn M, Wallensten A, Widerström M, et al (2015) Post-infection symptoms following two 
large waterborne outbreaks of Cryptosporidium hominis in Northern Sweden, 2010-2011. 
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from:  (Accessed 25 February 2019)
Sack DA, Tacket CO, Cohen MB, et al (1998) Validation of a volunteer model of cholera 
with frozen bacteria as the challenge. Infect Immun p. 1968-72.
Smith NH, Cron S, Valdez LM, et al (1998) Combination drug therapy for cryptosporidiosis 
in AIDS. J Infect Dis p. 900-3.
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Cryptosporidium parvum infection: a 1-year follow-up of outbreak associated cases. Journal 
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Vaccine Clinical Trials (2007). Guidance for Industry. U.S. Food and Drug Administration 
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Tribble DR, Baqar S, Carmolli MP, et al (2009) Campylobacter jejuni strain CG8421: a 
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16
Appendices
16.1
Appendix 1: Stool Grading System
All collected stool samples will be graded according to the system detailed below. Stools will 
be graded according to this Stool Grading System by the Investigator. Grades 1 and 2 are 
considered normal stool and Grades 3-5 are considered diarrheal stool.
Table 16-1
Stool Grading System
Clinical Stool Classification 
Stool Grade
Stool Description
Normal stool
1
Formed stool which does not 
take the shape of the container
Normal stool 
2 
Soft stool which does not easily 
take the shape of the container
Diarrheal stool 
3 
Thick liquid stool which does 
take the shape of the container
Diarrheal stool 
4
Opaque watery stool
Diarrheal stool 
5
Rice water stool, clear watery 
stool
Levine et al 1988, Sack et al 1998, Tribble et al 2009