Clinical trial NCT05205941
Conditions: Malaria
Keywords: Tolerability Safety
Sponsor: Medicines for Malaria Venture
Start date: 2022-03-30; Completion date: 2022-09-02
Enrollment: 9 participants; Allocation: NA; Intervention model: SEQUENTIAL

Brief summary:
A Phase 1b study to assess the safety, tolerability and antimalarial activity of MMV533 against Plasmodium falciparum 3D7 blood stage infection in healthy volunteers

Detailed description:
The study will characterise the effects of single oral doses of MMV533 on the clearance of Plasmodium falciparum 3D7 using the Induced Blood Stage Malaria (IBSM) model. This is a well-established method for obtaining useful pharmacokinetic-pharmacodynamic (PK-PD) information on anti-malarial drugs.

The study will be an open-label, pilot Volunteer Infection Study (VIS) using the IBSM model and single dose IMP. The study will be conducted in healthy malaria-naive adult volunteers infected with Plasmodium falciparum 3D7, in one cohort of approximately 12 volunteers (all receiving active treatment). From an operational perspective, the full cohort may be conducted in subgroups of up to 6 volunteers. Ascending doses will be administered in order of enrolment number (per sub-group, if applicable). Volunteers will be enrolled within a 28 day screening period to ensure volunteers meet all the inclusion criteria and none of the exclusion criteria.

On Day -8 (8 days prior to IMP administration), volunteers will attend the clinical unit to be inoculated with the malaria challenge agent containing approximately 2,800 viable human erythrocytes infected with P. falciparum 3D7 parasites. Parasitaemia will be monitored on an outpatient basis daily on Day -4, and then twice daily on Day -3, Day -2 and until admission to the clinical unit on Day -1 for eligibility check and confinement.

Volunteers will be administered IMP on Day 1 and will have safety monitoring and blood sampling for parasitaemia monitoring and PK analysis on an inpatient basis for at least 108 hours post-IMP administration. Volunteers will be discharged from the clinical unit after review of ECG, vital signs, clinical and laboratory tests safety data by the Principal Investigator or delegate, and will then attend the clinical unit on an outpatient basis regularly for continued safety monitoring and blood sampling for parasitaemia monitoring and PK analysis.

Volunteers will be administered mandatory malaria rescue medication at Day 21±3, or earlier if there is failure to clear parasites or recrudescence and at the discretion of the Principal Investigator or delegate. EOS will be on Day 28±3. Volunteers must have had at least two negative 18S qPCR (18 Svedberg quantitative polymerase chain reaction) results prior to EOS and must have completed their course of anti-malarial rescue medication.

In the event of recrudescence, blood samples will be collected prior to rescue treatment to culture parasites for drug resistance testing.

Arms: arm 1: Approximately 12 volunteers in 1 cohort, Up to six dose levels between 10 and 160mg
Interventions: intervention 1: MMV688533
Intervention descriptions: intervention 1: Not exceeding 200mg

Protocol documents:
ICF_002.pdf: 
 
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Page 1 of 32 
Document No. SPFMA001-03 
Implementation Date: 22-May-2020 
 
 
 
Participant Information and Consent Form 
 
Alfred Project Number
125/21
Full Study Title: 
A Phase 1b study to assess the safety, tolerability and antimalarial activity
of MMV533 against Plasmodium falciparum 3D7 blood stage infection in 
healthy volunteers. 
Protocol Number:
MMV_MMV533_20_01
Test Drug Code:
MMV533
International Sponsor:
Medicines for Malaria Venture (MMV)
Local Sponsor:
Southern Star Research Pty Ltd (SSR)
Coordinating Principal 
Investigator: 
Dr Paul Griffin 
Principal Investigator:
Dr Paul Griffin
Location: 
Q-Pharm Pty Ltd, Level 5 Clive Berghofer Cancer Research Centre, (CBCRC) 
300C Herston Rd, Herston QLD, 4006  
 
PART 1 - What does my participation involve? 
 
1. 
Introduction 
You are invited to take part in this research study because you are a healthy male or female aged 18-55 
years old who potentially meets the study participation requirements. 
 
This project is testing the safety, tolerability, pharmacokinetics (PK, the amount of study drug in your 
blood) and pharmacodynamics (PD, how the study drug affects your body and, in our case, the malaria 
parasite) of a single oral dose of a new drug called MMV533. The study drug is being developed as a 
potential new treatment for acute uncomplicated malaria. You will be inoculated with Plasmodium 
falciparum 3D7 prior to receiving the study drug. 
 
This Participant Information and Consent Form (PICF) tells you about the research study. It also explains 
the tests and treatments that will be completed during study participation. This information is given to you 
to help you decide if you want to take part in this research study. Please read this information carefully and 
ask the study doctor questions about anything that you don’t understand or want to know more about 
before deciding whether or not you want to take part. If you wish to do so, please take the time to talk 
about it with a relative, friend or your local doctor before making a decision to participate. 
 
Once you understand what the study is about and if you agree to take part in it, you will be asked to sign a 
Consent Form attached to this document. By signing the Consent Form, you indicate that you understand 
the information and that you give your consent to participate in the research study. 
 
Upon your confirmation, your information regarding participation in the study will be provided to your 
preferred doctor if you provide their contact details to study staff. It is desirable that your local doctor be 
advised of your decision to participate in this research study. 
 
Participation in this research is voluntary. If you don’t wish to take part, you don’t have to. 


 
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If you decide you want to take part in the research study, you will be asked to sign the consent section. By 
signing it you are telling us that you: 
 
understand the information you have read; 
 
consent to take part in the research study; 
 
consent to follow the study requirements; 
 
consent to have the tests and treatments that are described; 
 
consent to follow the study requirements and to keep follow-up appointments that are described; 
 
consent to the use of your personal and health information as described. 
A description of this clinical trial is available on https://clinicaltrials.gov/. This website will not include 
information that can identify you. At most, the website will include a summary of the results after the trial 
is completed. You can search this website at any time. 
 
You will be given a signed copy of the Participant Information and Consent Form to keep. 
 
2. 
What is the purpose of this research? 
Malaria is an infectious disease caused by Plasmodium parasites that are carried by Anopheles mosquitoes. 
At least five types of Plasmodium parasites can cause malaria in humans. In natural infections, the malaria 
parasite is injected into the blood when an infected Anopheles mosquito bites its victim. Anopheles 
mosquitoes are mostly found in hot and humid regions of the world, but they do not live in Brisbane 
(however, they do live in far north Queensland).  
Unfortunately, current approaches to controlling malaria in endemic areas (in regions where malaria is 
naturally present, for example South East Asia or Africa) are failing because the malaria parasites have 
become resistant or are becoming resistant to the antimalarial drugs we have available (this means the 
parasites are no longer killed by the drugs or they take longer to be killed by the drugs). Therefore, there is 
a need to develop and test new antimalarial drugs or combinations of drugs. One way of accelerating this 
process is to test the drugs in healthy volunteers who have been deliberately given malaria under well-
controlled experimental conditions. To do this, we introduce, using controlled intravenous (directly into a 
vein) administration, very small quantities of parasite to healthy volunteer adults. We call this process the 
Induced Blood Stage Malaria (IBSM) model. 
Medicines for Malaria Venture (MMV) is developing the study drug MMV533 as one such potential new 
oral treatment for the treatment of acute uncomplicated malaria. In this study, we will use the IBSM model 
to investigate whether MMV533 is able to eliminate the plasmodium parasite after single oral dose in 
healthy volunteers. 
Medications, drugs and devices must be approved for use by the Australian Federal Government; the 
Therapeutic Goods Administration (TGA). MMV533 has not been approved for marketing by the TGA in 
Australia (and is not yet approved anywhere else in the world). Therefore, the use of MMV533 in this study 
is experimental. 
MMV533 is being tested in humans in the ongoing First-in-Human (FIH) study investigating safety, 
tolerability and pharmacokinetics of MMV533 in healthy adult male and female volunteers. This study is 
also conducted in Australia (Melbourne). The six cohorts (5, 10, 20, 50, 100, and 160 mg) of the MMV533 
FIH study have been completed (total of n=48 volunteers; 12 placebo and 36 study drug). No serious or 
severe adverse events were observed and the drug was associated with a good safety profile including the 


 
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highest dose of 160 mg. This study is blinded which means that we do not know yet who has received the 
active drug or a placebo. 
 
In other studies, with drugs under development, some unexpected serious, life-threatening side effects 
have occurred following the administration of new experimental treatments. It is unknown, whether some 
unexpected, serious, life threatening side effects could occur with MMV533. Whilst these are considered 
unlikely, you will be monitored closely for them and treated if they occur.  
 
This study is being conducted at Q-Pharm Pty Ltd. The Clinical Research Organisation involved in monitoring 
the study and acting as the local sponsor is Southern Star Research (SSR) and is sponsored by Medicines for 
Malaria Venture (hereafter referred to as MMV).  
 
 
3. 
What does participation in this research involve? 
Before you begin the study, you will be given detailed information about MMV533, the study, and any other 
relevant information by research staff. You are encouraged to ask questions until you are sure that you 
fully understand the nature of and requirements of the study. 
 
If you decide to be assessed for inclusion in the study, you will be asked to visit Q-Pharm Pty Ltd. for an 
initial assessment visit (screening visit). Before any procedures are undertaken, you will be asked to sign a 
consent form. You will then have some tests to check that the study is suitable for you. The screening visit 
may take approximately 3 hours. 
 
Participants deemed eligible after screening will be inoculated with the malaria challenge agent on Day -8 
and first MMV533 dose will be given on Day 1. All safety checks will be performed during the study. Details 
of the study sequence and assessments in each visit are outlined below.  
 
Approximately 12 participants in 1 cohort (group) will be enrolled. Participants will be tested and dosed in 
subgroups of 4 to 6. The doses that will be evaluated in this study have all been tested in the initial "First-
In-Human" study (conducted in Melbourne) and have been be considered safe and well tolerated for 
human volunteers. 
 
The dose levels planned for this study range from 10 mg to 160 mg. Preliminary data from the First In 
Human study have shown that 160 mg is well tolerated in healthy volunteers. You will be informed of the 
exact dose for your cohort when you check in to the clinical unit (Day -1).  
 
Study sequence: 
Your total participation in the study will consist of approximately 10 weeks as follows;  
 
Screening visit: Will occur within 36 days of your first dose. You will undergo assessments to 
determine if you are eligible for the study.  
 
Pre-inoculation: You will be required to attend the study centre on a single occasion (Day -11, Day 
-10, or Day -9) 
 
Inoculation: You will be required to attend the study centre on a single occasion 
 
Post-inoculation: You will be required to attend the study centre on 3 separate occasions 
 
Admission and treatment period: You will be required to attend the study centre for a 5 night, in 
patient stay. 
 
Follow up visits: You will be required to attend the study centre on a maximum of 10 separate 
occasions following your discharge after Day 5.  
 


 
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Below is a schematic outlining the study schedule:  
*Follow up visits on Day 8, 14, 21, 25, and 28 are mandatory. Additional follow-up visits on Day 6, 7, 10, 12, 
and 18 may be required by the study doctor. The study doctor will tell you which of these additional visits 
you will need to attend. 
If you decide to be assessed for inclusion into the study, you will be asked to visit Q-Pharm Pty Ltd. for the 
screening visit.  
 
Screening visit (between Day -36 to Day -12) 
After reading this information sheet and if you agree to participate in the study, you will be asked to sign 
the attached consent form. The study doctor will perform a medical examination to ensure that it is 
appropriate for you to be part of the study. You will undergo the following assessments: 
 
You will be asked about your current health status and about your medical/surgical history, 
including all medications, over-the-counter and herbal medications that you have been, and are 
currently taking. 
 
You will be asked some personal details about yourself, including your date of birth. 
 
For your own health and for correct operation of the study, it is important that you are honest and 
complete with your answers. You may be asked about your use of tobacco (including e-cigarettes 
and other nicotine products), alcohol and other drugs. You will undergo an alcohol breath test. 
 
You will be asked to provide a urine sample to assess your general health and to test for 
substances/drugs of addiction as listed below: 
- 
to test for substances/drugs of addiction (such as amphetamines, methamphetamines, 
barbiturates, 
benzodiazepines, 
cocaine, 
methadone, 
opiates, 
phencyclidine 
and 
tetrahydrocannabinol). This is a study requirement and the results will remain confidential. The 
tests may reveal that you have previously used legal or illegal substances. That information will 
be stored in a re-identifiable (or coded) format. If Q-Pharm Pty Ltd. is ordered by a court of law  
to disclose the information regarding the use of illegal medications or alcohol breath test  
levels, it may be used against you in legal proceedings or otherwise as the court directs. If you 
test positive for any of these substances, you will be excluded from further participation in this 
study. 
- 
to test for use of tricyclic antidepressants  
 
Your vital signs such as blood pressure, pulse rate and body temperature will be measured.  
 
You will have a full physical examination (PE), including measurement of your height and weight 
to determine your body mass index (BMI). 
Screening Visit: 
Day -36 to -12
Pre-inoculation
Day -11 to -9
Inoculation
Day -8
Telephone 
follow-up
Day -7 to Day -5
Post-
inoculation
Day -4 to -2
Admission and treatment period
Admit: Day -1
Dose: Day 1
Discharge: Day 5
Follow up visits*
Day 6, 7, 8, 10, 12, 14, 18, 21, 25 and 28


 
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 
G6PD status testing:  Severe G6PD deficiency (a condition that may potentially have impact on 
your red blood cells during the study) diagnosed through a blood test at screening is an exclusion 
criteria due to increased risk in case of malaria infection.  
 
Red blood cells antibodies: It is possible that you could suffer a transfusion reaction after being 
inoculated with the malaria challenge agent, or develop alloantibodies to the donor red blood cells 
(RBCs) that may make blood transfusion more difficult for you in the future. The risk of developing 
such alloantibodies is considered extremely low as the donor blood used to produce the malaria 
challenge agent was blood group O Rh(D) negative which is generally considered to be a ‘universal 
donor’. 
- 
As part of the safety monitoring for this study, you will be tested for RBC alloantibodies at 
screening and then at the end of the study, and will be monitored for signs and symptoms of 
transfusion reactions immediately after being inoculated with the malaria challenge agent. 
 
Pregnancy test: If you are a woman, your blood will be tested to check that you are not pregnant. 
If you are a woman of non-childbearing potential, your blood will be tested to confirm your 
postmenopausal status. 
 
You will have electrocardiograms (ECG) (recording of your heart’s electrical activity and rhythm).   
 
Safety Lab Test Blood sample will be collected for screening for HIV (AIDS virus), and hepatitis B 
and C and general safety assessments. This is because the study doctors need to know about your 
general health and the health of your immune system. 
o You will receive information and counselling before the HIV and hepatitis tests. If a test 
shows you have HIV or hepatitis you will not be included in this study, but you will have 
follow-up counselling and medical advice. If your test results are positive, the researchers 
are required by law to notify the relevant state government. Signing the consent form 
means you agree to have this testing. It will not be done without your consent. 
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Questionnaire: you will be asked questions by the site staff as part of a questionnaire called the 
Beck Depression inventory to assess your mental health. The purpose of this questionnaire is to 
ensure that participants do not have mood disorders while enrolled in the study. 
 
Concomitant Medication (all medications, supplements and herbal preparations) review: you will 
be asked if you have recently taken any medications as this may interact with the study drug. 
 
Adverse Events: You will be asked about how you are feeling (whether you feel alright, different 
from normal or unwell), please tell a study team member if you have any changes in your health or 
concerns.  
If for any reason, the trial is found to not be suitable for you, staff from Q-Pharm Pty Ltd. will contact you. 
 
Pre-inoculation Day (Three options: Day -11, Day -10 or Day -9) 
 
You will be asked about your current health status and about your medical/surgical history, 
including all medications, over-the-counter and herbal medications that you have been, and are 
currently taking. 
 
Questionnaire: you will be asked questions by the site staff as part of a questionnaire called the 
Beck Depression inventory to assess your mental health.  
 
Physical Examination: will be performed to assess your general health. This will include 
measuring your body weight. 


 
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 
Body Temperature: your body temperature will be measured 
 
Safety blood and urine samples: a blood and urine sample will be collected to assess your 
general health. You will need to have fasted from all food and drink (except water) for at least 8 
hours before providing blood samples. 
 
You will have electrocardiograms (ECG) (recording of your heart’s electrical activity and rhythm).   
 
Pregnancy test: If you are a woman, your blood will be tested to check that you are not pregnant. 
If you are a woman of non-childbearing potential, your blood will be tested to confirm your 
postmenopausal status. 
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Concomitant Medication (all medications, supplements and herbal preparations) review: you will 
be asked if you have recently taken any medications as this may interact with the study drug. 
 
Adverse Events: You will be asked about how you are feeling (whether you feel alright, different 
from normal or unwell), please tell a study team member if you have any changes in your health or 
concerns.  
Inoculation (Day -8) 
To ensure sufficient number of participants are available for inoculation Day -8, additional volunteers called 
‘alternates’ will be recruited. If you are an alternate, you may be asked to participate in the study if 
someone is not included in the inoculation group. You will be informed if you are an alternate on Day -8 
before being inoculated. 
 
You will be asked about your current health status and about your medical/surgical history, 
including all medications, over-the-counter and herbal medications that you have been, and are 
currently taking. 
 
Physical Examination: will be performed to assess your general health.  
 
You will be asked to provide a urine sample to test for substances/drugs of addiction and undergo 
an alcohol breath test 
 
Your vital signs such as blood pressure, pulse rate and body temperature will be measured.  
 
12-Lead Electrocardiogram (ECG): to assess your heart rhythm. 
 
Serum Safety samples: two blood samples will be taken for safety assessments related to the study 
drug and the malaria challenge agent.  
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Malaria clinical score: The Malaria Clinical Score will be used to quantify any signs and symptoms 
of malaria after you have been inoculated with the malaria challenge agent. You will be asked to 
grade your signs/symptoms using a 4-point scale (absent 0; mild: 1; moderate: 2; severe: 3). The 
total score covers 14 possible symptoms/signs associated with malaria. 
 
Pharmacodynamic (PD) blood samples also called "PCR samples": will be collected to quantify the 
malaria parasite in your blood and measure the treatment effect. Blood samples will be collected 
at various times during the study visits (as shown in the schedule below). 


 
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 
IV malaria challenge agent:  The malaria challenge agent is composed of approximately 2800 viable 
human red blood cells infected with the Plasmodium falciparum 3D7 parasite, and is administered 
intravenously to the participant as part of the IBSM model of controlled infection to help study the 
effectiveness of the test drug (MMV533). This parasite is highly sensitive to commercially available 
treatments for malaria. These registered treatments (called "definitive medication") will be also 
administered at the end of the study (or earlier based on blood tests) to ensure full elimination of 
the parasites once the study is completed.  
 
Diary card: You will be given a diary card and thermometer to collect information during outpatient 
periods including daily oral temperature, adverse events (including any signs/symptoms of 
malaria), details of self-administered take home malaria definitive medication and concomitant 
medications. You will be required to fill the diary out every day and bring your diary cards to each 
visit to the clinical trial unit for review. 
 
Concomitant Medication (all medications, supplements and herbal preparations) review: you will 
be asked if you have recently taken any medications as this may interact with the study drug. 
 
Adverse Events: You will be asked about how you are feeling (whether you feel alright, different 
from normal or unwell), please tell a study team member if you have any changes in your health or 
concerns. 
 
Telephone follow-up (Day -7 to Day -5) 
On Days -7, -6, and -5, you will be telephoned by Q-Pharm Pty Ltd. The purpose of this call is to find out 
how you are feeling and whether you have had any changes in your health. 
 
Post-inoculation (Day -4 to Day -2) 
You will  be required to attend the clinical unit for outpatient visits once (in the morning) on Day -4 and 
twice daily on Days -3 and -2 (separated by 12±2 hours on each day) 
 
Physical Examination: will be performed to assess your general health. 
 
Your vital signs such as blood pressure, pulse rate and body temperature will be measured.  
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Safety blood and urine samples (Day -3 only): a blood and urine sample will be collected to 
assess your general health.  
 
Diary card review:  You will be required to bring your diary cards to each visit to the clinical trial 
unit for review. 
 
Malaria clinical score: The Malaria Clinical Score will be used to quantify any signs and symptoms 
of malaria after you have been inoculated with the malaria challenge agent. You will be asked to 
grade your signs/symptoms using a 4-point scale (absent 0; mild: 1; moderate: 2; severe: 3). ). The 
total score covers 14 possible symptoms/signs associated with malaria. 
 
Pharmacodynamic (PD) blood samples: will be collected to assess the effects against malaria 
parasite. Blood samples will be collected at various times during the study visits (as shown in the 
schedule below). 


 
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 
Concomitant Medication (all medications, supplements and herbal preparations) review: you will 
be asked if you have recently taken any medications as this may interact with the study drug. 
 
Adverse Events: You will be asked about how you are feeling (whether you feel alright, different 
from normal or unwell), please tell a study team member if you have any changes in your health or 
concerns.  
 
Admission and treatment period (Day -1 to Day 5) 
You will be admitted to the clinical unit the day before the planned dosing day (Day -1). On Day -1 you will 
undergo a number of procedures to confirm your continued suitability for participation in the trial (see 
table below). 
You will be required to stay in the clinical unit for 5 consecutive nights and discharged home on the last day 
of treatment period.  
On your first day in the clinical unit Day -1, a cannula will be inserted into a vein in your arm. This is a small, 
tube which will allow blood to be collected easily throughout your unit stay and prevents the need for 
repeated needles to be inserted in your vein to collect each sample. The location of the cannula may need 
to be repositioned if required. 
During your stay in the clinical unit, you will be provided meals. For Day -1 only, you will need to arrive 
fasted from all food and drink (except water) for at least 8 hours before providing blood samples. 
You will undergo the following procedures at various times during the study:  
 
Your vital signs such as blood pressure, pulse rate and body temperature will be measured.  
 
12-Lead Electrocardiogram (ECG): to assess your heart rhythm. 
 
Physical Examination: to assess your general health.  
 
Body weight and height: Body weight (kg) will also be measured at eligibility visit between Days -
11 to -9 and at EOS. 
 
Safety blood and urine samples (Day -3 only): a blood and urine sample will be collected to 
assess your general health.  
 
You will be asked to provide a urine sample to test for substances/drugs of addiction 
 
Alcohol breath test: You will undergo an alcohol breath test when you check into the clinical unit 
to see if you have been drinking any alcohol in the past 24 hours. 
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Study drug administration: The study drug (MMV533) will be administered on Day 1 as an oral 
tablet with 240mL of water under fasting conditions (10 hrs overnight). You will be given a definitive 
medication on Day 21 (see page 8). 
 
Pregnancy test: If you are a woman, your urine will be tested to check that you are not pregnant.  
 
Diary card: You will be required to bring your diary cards to each visit to the clinical trial unit for 
review. 
 
Malaria clinical score: The Malaria Clinical Score will be used to quantify any signs and symptoms 
of malaria after you have been inoculated with the malaria challenge agent. You will be asked to 
grade your signs/symptoms using a 4-point scale (absent 0; mild: 1; moderate: 2; severe: 3). The 
total score covers 14 possible symptoms/signs associated with malaria. 


 
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 
Pharmacokinetic (PK) samples: will be collected to measure the amount of MMV533 in your blood, 
the break down products and to assess the effect it has on your body. Blood samples will be 
collected at various time points during a study visit (as shown in the schedule below).  
 
Pharmacodynamic (PD) blood samples: will be collected to assess the effects against malaria 
parasite. Blood samples will be collected at various times during the study visits (as shown in the 
schedule below). 
 
Concomitant Medication (all medications, supplements and herbal preparations) review: you will 
be asked if you have recently taken any medications as this may interact with the study.  
 
Adverse Events: You will be asked about how you are feeling (whether you feel alright, different 
from normal or unwell) at regular intervals, please tell a study team member if you have any 
changes in your health or concerns. 
 
You will be discharged from the clinical unit once all study procedures are complete and the clinical staff 
sees no changes in your health which would prevent your discharge from the clinical unit.  
 
Follow up visits (Day 5,+) 
You will be required to attend follow-up visits on up to 10 days at Q-Pharm Pty Ltd. The follow-up visits on 
Day 8, 14, 21, 25 and 28 are mandatory. Additional follow-up visits on Day 6, 7, 10, 12, and 18 may be 
required by the study doctor. The study doctor will tell you which of these additional visits you will need to 
attend. These visits will take approximately 1-2 hours for a range of follow-up assessments as outlined 
above and in the table below.  
 
 
Physical Examination: to assess your general health.  
 
Your vital signs such as blood pressure, pulse rate and body temperature will be measured.  
 
12-Lead Electrocardiogram (ECG): to assess your heart rhythm. 
 
Safety blood and urine samples:  blood and urine samples will be collected to assess your general 
health. 
 
Pharmacokinetic (PK) samples: will be collected to measure the amount of MMV533 in your blood, 
the break down products and to assess the effect it has on your body. Blood samples will be 
collected at various time points during a study visit (as shown in the schedule below).  
 
Pharmacodynamic (PD) blood samples: will be collected to assess the effects against malaria 
parasite. Blood samples will be collected at various times during the study visits (as shown in the 
schedule below). 
 
SARS-COV-2 (COVID-19) testing: A swab will be inserted into your throat or nose to collect a sample 
for a COVID-19 test. 
 
Malaria clinical score: The Malaria Clinical Score will be used to quantify any signs and symptoms 
of malaria after you have been inoculated with the malaria challenge agent. You will be asked to 
grade your signs/symptoms using a 4-point scale (absent 0; mild: 1; moderate: 2; severe: 3). The 
total score covers 14 possible symptoms/signs associated with malaria. 
 
Parasite drug resistance samples: One blood sample will be collected to investigate parasite drug 
resistance in the event there is a recurrence of infection with malaria detected through a blood test 
(i.e., “Pharmacodynamic blood sample”).    


 
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 
Definitive medication:  when your test results reach a certain value, you will be given a definitive 
medication against malaria as a preventative measure. This could be on any day within this follow 
up period. You will be required to consume 240 mL full-fat milk with each dose of definitive 
medication. 
At your final follow up visit, blood samples will be collected to ensure that you are fully clear of malaria. 
If there is any follow up needed, this will be communicated to you by the study staff/ study doctor.  
 
The study doctor will ask you to return to the research unit on these days and may ask you to return after 
this period, if he/she feels it is necessary. In the event it is necessary to further evaluate the safety or effects 
of the medication, it may be necessary to have access to additional information about your health status. 
Your study doctor may attempt to obtain study-related information about your health from you or from 
other sources, including your primary care physician. This may include contacting you again by phone or 
letter. 
 
Total Blood Volume Collected Throughout Study 
 
By consenting to take part in this study, you also consent to the collection and testing of your urine and 
blood samples and COVID tests (swabs/blood) for this research. The volume of blood to be collected during 
the study will not exceed 450mL. For comparison, a standard blood donation is approximately 470mL 
(approx. 2 cups). 
 
The total volume does not account for a small amount of blood (approx. 2ml per collection) which is 
discarded (each time) when a cannula is used to collect the blood.  
Please note that as per the Investigators discretion, additional blood samples may also be collected for 
safety reasons.  


 
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The table below outlines the assessments that will be performed during the study: 
 
Screening 
Pre-
inoculation 
Inocula 
tion 
Post-inoculation 
Phase 
Treatment and Posttreatment phase 
EOS/
ET
Day 
D-36 to D-
12 
D-11 to D-9 
D-8 
D-4 
D 
-3 
D 
-2 
D 
-1 
D1 
D
2
D
3 
D
4 
D
5 
D
6 
D
7 
D8 
± 2 
D10 
D12 
D14
± 2 
D18 
D21
± 3 
D25
± 3 
D28 
± 3
Informed consent
X
Confinement
X
X
X
X
X
X
Discharge
X
Outpatient visit at clinical 
site 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inclusion/exclusion 
criteria
X 
X 
X pre 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical history
X
X
X pre
BDI-II
X
Prior/concomitant 
medications
X 
X 
X pre 
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study treatment 
administration
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV malaria challenge agent
X
MMV533 (IMP)
X
Definitive medication 
Xa
Safety 
Physical exam - full
X
X
Physical exam – symptom 
directed
 
X 
X 
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height
X
Body weight
X
X
X
G6PD status testing
X
Red blood cells antibodies
X
X
Serology tests
X
X
Urine drug screen, alcohol 
test
X 
 
X pre 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs supine and 
standing
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs supine 
 
 
X pre & 
post
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre
X 
 
12-lead ECG 
X 
X 
X pre 
 
 
 
X 
X 
X
X 
X 
X 
 
 
X 
 
 
X 
 
X 
pre
X 
X 
Body temperatur 
X 
X 
X pre 
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre
X 
X 
Hematology, biochemistry 
X 
X 
 
 
X 
 
X 
X 
X
X 
X 
X 
 
 
X 
 
 
X 
 
X 
pre
X 
X 
Urinalysis 
X 
X 
 
 
 
 
X 
X 
X
 
X 
 
 
 
X 
 
 
X 
 
X 
pre
 
X 


 
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Screening 
Pre-
inoculation 
Inocula 
tion 
Post-inoculation 
Phase 
Treatment and Posttreatment phase 
EOS/
ET
Day 
D-36 to D-
12 
D-11 to D-9 
D-8 
D-4 
D 
-3 
D 
-2 
D 
-1 
D1 
D
2
D
3 
D
4 
D
5 
D
6 
D
7 
D8 
± 2 
D10 
D12 
D14
± 2 
D18 
D21
± 3 
D25
± 3 
D28 
± 3
Coagulation
X
Pregnancy Test/ FSH
X
X
X
X
SARS-CoV-2 Testing
X
X
X pre
X
X
X
Serum Safety samples 
 
 
X pre 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XErr
or! 
Refer
ence 
sourc
e not 
found
.
Diary card 
 
 
X post 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
pre
X 
X 
Malaria clinical score 
 
 
X pre & 
post
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre
X 
X 
Adverse event collection
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics 
MMV533 + metabolites 
plasma samples
 
 
 
 
 
 
 
X 
X
X 
X 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Pharmacodynamics 
Parasitaemia by 18S qPCR
X pre
X
X
X
X
X
X
X
X
X
X
X
Xa
Xa
Xa
Xa
Xa
X
X
X
Gametocytaemia by qRT-
PCR pfs25
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Exploratory 
Parasite drug resistance 
samples 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABBREVIATIONS: BDI-II = Beck Depression Inventory; ECG = Electrocardiogram; EOS = End of study visit; ET = early termination visit; FSH = follicle stimulating hormone; IMP= 
Investigational Medicinal Product; qPCR =quantitative polymerase chain reaction; RT-PCR pfs25= gametocyte-specific mRNA transcript pfs25


 
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4. 
What do I have to do? 
It is important for your own safety that you inform the study doctor or staff of your complete medical 
history and all medications, supplements, and/or herbal preparations that you have taken within the 
past 6 months or are currently taking. If you have any health problems, please notify your study doctor 
immediately. As mentioned earlier in this document, if you notice any changes in your health or have 
concerns during your participation in the study, also inform your study doctor or study staff as soon 
as possible. You must always follow the instructions of the study doctor and staff. 
 
Please note that in the days leading up to your admission to the clinical unit, there are a few things 
you must avoid to be included in the study: 
 
You should not have participated in any investigational product study within the 12 weeks 
preceding inoculation with the malaria challenge agent or 5 times the half-life of the 
Investigational product, whichever is longer. The half-life of a drug is the time it takes for the 
levels of the drug in your system to decrease by half. Your study doctor from your previous 
clinical trial should be able to tell you how long 5 half-lives would last 
 
You must not have any history of malaria or participation in a previous malaria challenge study 
or malaria vaccine trial 
 
You must not have received (or plan to receive) any vaccination (excluding COVID-19 vaccine) 
within 28 days of study drug dosing 
 
You MUST be fully vaccinated against COVID-19 including a booster shot (e.g. 3 doses of 
vaccine), with the most recent dose administered at least 14 days prior to inoculation of the 
malaria challenge agent.  
 
You must not have previously received a blood transfusion 
 
You must not have used antibiotics within 6 weeks of Screening 
 
You must not have used systemic therapies with antimalarial activity within 6 weeks of 
Screening. This includes (but not limited to) artemisinin, amodiaquine, atovaquone, 
chloroquine, mefloquine, mepacrine, primaquine, proguanil, quinine, sulfadoxine-
pyrimethamine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, 
clindamycin, doxycycline, and tafenoquine.  
 
You must not have had any systemic administration (oral, pulmonary/nasal, IV) of 
corticosteroids, anti-inflammatory drugs (excluding commonly used over-the-counter anti-
inflammatory drugs such as ibuprofen, acetylsalicylic acid, diclofenac), immunomodulators 
or anticoagulants within the past three months. 
 
You must not have had any topical administration (cutaneous, eye drops) of corticosteroids  
within the past 2 weeks.  
 
You must not currently be receiving or having previously received immunosuppressive 
therapy (including systemic steroids, adrenocorticotrophic hormone or inhaled steroids) at a 
dose or duration potentially associated with hypothalamic-pituitary-adrenal axis suppression 
within the past 12 months. 
 
You must not have donated any blood within one month before screening, or participation in 
any research study involving blood sampling (more than 450 mL/unit of blood) 
 
You must not consume any citrus fruits (grapefruit, Seville oranges, cranberry, pomegranate,  
star fruit, exotic fruits, pomelos, marmalade) or their juices, or herbal medications (such as St 
Johns wort) during the study and within 7 days prior to study drug administration (Day -1).  
 
You must not consume poppy seeds in the 24 hours prior to screening, day of admission, for 
confinement, for IMP administration (Day -1) and day of first dose of definitive medication. 


 
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 
You must not consume food or beverages containing alcohol 24 hours prior to each alcohol 
breath test and for the entire period of confinement at the clinical unit 
o You should not drink more than 2 standard drinks per day and no more than 10 
standard drinks per week from 24 hours prior to inoculation with the malaria 
challenge agent on Day -8, and after discharge from confinement until the end of 
treatment with definitive medication 
 
You must not consume food or beverages containing quinine, such as tonic water or lemon 
bitter, from the day of inoculation with the malaria challenge agent (Day -8) until after 
definitive medication has completed 
 
You must not consume beverages containing xanthine bases (eg, Red Bull, coffee) during the 
entire period of confinement. You should not consume more than 400 mg caffeine per day 
(equivalent to more than 4 cups of coffee) from inoculation with the malaria challenge agent 
on Day -8 until admission for confinement at the clinical unit (Day -1), and after being released 
from confinement at the clinical unit on Day 5 until the end of treatment with definitive 
medication 
 
You must not use tobacco during confinement at the clinical unit for IMP administration (Day 
-1 to Day 5). You should not smoke more than 5 cigarettes (or equivalent) per day until Day -
1 and after being discharged from confinement at the clinical unit on Day 5 until  the end of 
treatment definitive medication.  
 
You must abstain from strenuous exercise sessions for 4 days prior to study drug 
administration until Day 14. 
 
You must not use any illicit substances for the entire study period  
 
All meals and beverages during your stay at the study centre will be provided. You must not consume 
any other food or beverage whilst in the study centre unless directed by study staff.  
Please note that you will not be allowed to smoke while at the study centre. 
In case of emergency, you must be easily contactable by phone and/or email. You will be given a 
Participant Wallet Card which contains emergency contact information and information about your 
study commitments. You must carry the Participant Wallet Card with you at all times until the end of 
the study. 
 
5. 
Other relevant information about the research study 
This study is being conducted at Q-Pharm Pty Ltd. in Australia. Researchers from Nucleus Network Pty 
Ltd (located in Melbourne, Victoria) and Q-Pharm Pty Ltd (located in Queensland), both Nucleus 
Network companies, will be working in collaboration. A malaria expert (Dr Bridget Barber / QIMR - 
Brisbane) will be also supporting this study. 
 
A representative of MMV (study sponsor) may be present for inspections in the unit during the study. 
 
6. 
Do I have to take part in this research study? 
Participation in any research study is voluntary. If you do not wish to take part, you don’t have to. If 
you decide to take part and later change your mind, you are free to withdraw from the study at any 
time without providing any reason. Your study doctor may ask you the reason for your withdrawal; 
you can answer or not.  
 


 
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Your decision whether to take part or not, or to take part and then withdraw, will not affect your 
relationship with Q-Pharm Pty Ltd. and will not involve any penalty or loss of benefits to which you 
would be otherwise entitled. Should you withdraw from the study before the final visit you will receive 
a partial payment according to the number of visits you have attended. 
 
Before you make your decision, a member of the research team will be available so that you can ask 
any questions you have about the research study. You can ask for any information you want. Sign the 
Consent Form only if you agree to participate and only after you have had a chance to ask your 
questions and have received satisfactory answers. 
 
7. 
What are the alternatives to participation? 
Since this study is intended only to evaluate the safety, tolerability, pharmacokinetics and 
pharmacodynamics of MMV533, the alternative to being a participant in this study is to choose not to 
participate in the study. 
 
8. 
What are the possible benefits of taking part? 
If you agree to take part in this study, there will be no direct benefit to you. However, your 
participation in this study may help develop important scientific knowledge that could contribute to 
the development of a treatment for Malaria. We hope the information learned from this study will 
benefit others in the future. 
9. 
What are the possible risks and disadvantages of taking part? 
MMV533 is an experimental medication which has been evaluated in a small number of healthy 
volunteers (less than 50), therefore the risks to human participants have not been fully evaluated. 
 
Medical treatments often cause side effects. You may have none, some or all of the effects listed 
below, and they may be mild, moderate or severe. If you have any of these side effects, or are worried 
about them, talk with a study doctor. Your study doctor and study staff will also be watching you 
closely for side effects. 
 
Many side effects go away shortly after treatment ends. However, sometimes side effects can be 
serious, long lasting or permanent. If a severe side effect or reaction occurs, your study doctor may 
need to stop your involvement in the study. Tell your study doctor or site staff if you notice any 
changes in your health or have concerns. Your study doctor will discuss the best way of managing any 
side effects with you. 
 
There may also be side effects that are not expected or are not known that may be serious. Tell your 
study doctor immediately about any new or unusual symptoms or changes in your health that you 
become aware of. The treatment of the side effects will depend on the type and severity of the 
symptom(s). 
 
If during screening or participation in this research study a previously unknown medical condition is 
discovered the study doctor will discuss: 
 
whether you are eligible for study participation  
 
if you require referral to your usual doctor or to a specialist 
 
 
 


 
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Risks of Malaria Inoculation 
The study involves you being injected with malaria parasites that are contained in human red blood 
cells. These red blood cells were collected from a volunteer who got malaria when they were bitten by 
an infected mosquito. This raises several possible risks:  
Potential risks of receiving red blood cells from a donor 
 
The risk of infection with viruses or organisms (other than malaria) from the very small quantity of 
blood injected into you in this study is much smaller than the risk of infection from a blood 
transfusion for reasons described: 
o The volume of blood used to transmit the malaria in this study is many thousands of times 
smaller than what would be used in a whole blood transfusion and so the risk is reduced.  
o The blood cells have been washed and the white cells have been removed, both of which lower 
the risk of infection due to transfusion.  
o Before this initial volunteer donor was infected with malaria, the volunteer was screened for a 
wide range of blood borne diseases. After the malaria-infected blood was collected, it was 
frozen for over a year so that the donor could be observed and retested for any infections. 
During this time the donor remained healthy, and repeat testing after one year did not reveal 
any new infections. This last point is significant as this indicated that the volunteer’s malaria 
infected blood did not contain any low-level infections with viruses or other organisms at the 
time of collection that did not show up on the initial tests. This is especially important in 
reducing the risk of transfusion associated infection.  
o Over 401 people have received this malaria parasite and none have developed a blood-borne 
infection because of it. 
 
The risk of a transfusion reaction (similar to an allergic reaction) is unlikely because of the extremely 
small quantity of donor blood in the inoculum, and because the white cells have been removed 
from the donor blood. Nevertheless, you will be monitored closely for one hour after you are given 
the malaria parasite dose.  
 
The risk that you could develop antibodies (a protein that can protect the body from foreign 
organisms, such as bacteria and viruses) to the donor red cells is also very small because the donor 
of the red cells was blood group O and Rh negative. People with blood group O blood are 
considered ‘universal donors’, as people who receive even large volumes of blood from them are 
unlikely to develop red cell antibodies. Nevertheless, as a precaution, you will be tested for red cell 
antibodies before and after the study. Women of childbearing potential have a small additional risk 
of developing red cell antibodies that could cause problems during pregnancy. Women of 
childbearing potential have participated in several malaria challenge studies with P. falciparum 3D7 
with no known issues to date. If you are a woman of childbearing potential, you will be required to 
comply with strict contraception requirements during the study. 
 
 
 


 
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The risk of malaria 
Untreated P. falciparum malaria infection can be fatal.  
In this study, to ensure your safety, blood samples will be taken to monitor the number of parasites in 
your blood after you receive the malaria inoculum. You will be closely monitored for any early 
symptoms of malaria (like fever, aches and pains, headache).  
The parasites you will receive are known to be 100% cleared by the standard antimalarial medications 
that you will receive after administration with MMV533. The strain of parasite you will be given has 
been used in 401 participants in 30 malaria studies, most of which were conducted at the clinical trial 
site and QIMR Berghofer. 
Also, the number of parasites administered to participants in the study is much lower than the number 
of parasites that reach the blood after the bite of a single malaria-infected mosquito. Most previous 
participants have no or only mild symptoms due to the low number of parasites. Some people do 
however experience flu-like symptoms prior to antimalarial treatment, or a brief fever after the 
antimalarial treatment as the malaria parasite is killed and the immune system is activated. These 
episodes may require treatment, for example a medication for fever, in which case ibuprofen is 
preferred to paracetamol.  
Adverse effects observed during previous studies (where malaria is inoculated via infected red blood 
cells or via mosquito bites) 
Temporary changes in blood tests are regularly observed during malaria challenge studies. These 
include decreased white blood cells and platelets, which always return to normal by the end of these 
studies. These blood test changes are also seen in natural malaria infection.  
Among the 401 healthy participants who have received the P. falciparum inoculum (3D7 strain) in drug 
studies, a small portion (less than 5%) have shown moderate or severe elevations of liver enzymes a 
few days after antimalarial treatment. Although some of these elevations have reached values in the 
range 5-10 times the normal levels (i.e., severe elevations), they have not been caused any symptoms, 
and results have returned to normal before the end of the study without any specific treatment.  
It is unclear why some participants show these biological changes: a contribution of the malaria, of 
paracetamol and/or the drugs tested cannot be excluded. Liver experts have reviewed the data and 
believe that the changes are most likely due to the response to the malaria infection rather than being 
caused by the drug. These changes are also seen in naturally acquired malaria and return to normal in 
these situations too. We will closely monitor your liver function tests during this study. If such 
elevations occur during the study, we will monitor your blood until these parameters are back to normal 
values. 
One case of severe transient neutropenia (a decrease in a specific subset of White Blood Cell called 
neutrophils) has been also reported after malaria inoculation in one healthy participant. During the 
study and particularly after malaria inoculation, your blood cell count will be monitored at periodic 
intervals. Should this adverse event be observed, hospitalization for further monitoring could be 
considered due to a risk for further infections. 
There have been three unexpected cardiac serious adverse events in healthy participants infected in 
malaria challenge studies, using mosquito malaria inoculum (a slight variation to the blood stage 
malaria challenge in this study) that occurred in the Netherlands: 


 
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 
The first participant experienced an episode of chest pain, diagnosed as acute coronary syndrome 
(decreased blood flow to part of the heart muscle). This occurred two days after completion of 
malaria treatment. It is uncertain what caused the blood flow to be decreased. This could be due 
to the heart artery spasm or blockage, or cardiac inflammation. This participant was also found to 
be suffering with a viral upper respiratory tract infection (common cold virus) at the time. The 
individual was treated accordingly, with full recovery reported. 
 
The second participant was found to have an abnormal blood test suggesting cardiac inflammation. 
The individual subsequently suffered a very short episode of chest pain and was diagnosed with 
cardiac inflammation. This participant was also found to be suffering with a viral upper respiratory 
tract infection (common cold virus) at the time. Again, this second individual made a full recovery. 
 
More recently, a third participant also had an abnormal blood test suggesting mild cardiac 
inflammation. This participant also fully recovered.  
It is unclear at this stage whether these events were related to i) the experimental malaria vaccine the 
participants received, ii) the malaria infection, or iii) the malaria treatment, or were caused by 
something unrelated.  
In a recent trial at the clinical trial site, two participants developed cardiac adverse events: 
 
The first participant had an abnormal ECG prior to the antimalarial definitive drug. The participant 
did not have any symptoms at the time the abnormally fast heart rhythm with extra beats was 
noticed. Subsequent investigations did not find a significant cause of the abnormal heart rhythm.  
 
The second participant had an abnormal fast rhythm with extra beats at the same time point as the 
first participant. The participant had a temperature and required definitive treatment for the 
malaria. The abnormal heart rhythm went back into a normal heart rhythm after treatment.  
It was felt by an independent cardiologist and the study safety review team that the malaria infection 
had unmasked the unknown cardiac conditions that these subjects had prior to enrolment in the study. 
It was felt that these conditions would not have been picked up in the screening process. Nonetheless, 
as a precaution, we will exclude people at significant risk of heart disease from participating in this 
study. We will also monitor your heart using ECG at regular intervals and have a cardiologist available 
on call if a problem arises. 
There is no risk of developing malaria again from this study, as the final antimalarial drug treatment 
you will be given will completely cure you and these infections do not occur with P. falciparum malaria, 
which is the type of malaria parasite used in this study. 
Finally, although we consider that this study involves minimal risk, we cannot completely rule out the 
possibility of unforeseen side effects. 
 
 
 
 


 
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Risks of Study Drugs: 
1. Risks of MMV533 
 
A. Risks of the study drug (MMV533) based on related drugs and animal studies 
The mechanism of action of MMV533 against the malaria parasite is unknown and there are no 
other licensed medications on the market that act in a similar way. To assess the potential risk of 
treating humans with MMV533, non-clinical (i.e. animal) studies were conducted in two species (rats 
and dogs).  
In these animal studies, some unexpected serious side effects have occurred following the 
administration of MMV533 at drug levels that are higher than levels that will be reached in this 
current human study. These side effects observed in rats and dogs are considered unlikely to occur 
in humans; however, you will be monitored closely for all side effects and treated if they occur. 
Studies were conducted with repeated dose of MMV533. In these studies where animals were 
treated for 2 weeks, there were some transient changes in blood tests (liver enzymes and bile acids) 
without symptoms. There were minor changes seen in the bile ducts of dogs receiving MMV533 
(called hyperplasia) which where reversible when the drug was stopped.  
MMV533 may have side effects in humans, including side effects which are currently unknown. 
Based on the animal observations, the following effects may occur after single dose administration 
of MMV533: 
  
 
Elevated liver enzymes and bile acids in your blood, 
 
Temporary changes in liver tissue (a consequence of increased levels of bile acids), 
 
Changes in cardiac activity on electrocardiograms (called “QTc prolongation”), a condition 
which may lead to irregular heart beat (cardiac arrythmia). Your heart activity will be 
monitored closely during the study for any adverse cardiac activity.  
As a further precaution you will not be included on the study if you have any conditions that may put 
you at an increased risk of developing any of these effects. We will monitor these risks through 
regular blood samples and recordings of your cardiac activity. 
 
B.  Risks of the study drug (MMV533) based on preliminary human data 
Single dose administration of MMV533 was recently evaluated in the First-in-Human study 
MMV_MMV533_19_01 in Melbourne, Australia. Six dose levels, 5, 10, 20, 50, 100, and 160 mg 
MMV533, have been fully evaluated in six cohorts of 8 healthy volunteers (6 active drug/2 placebo). 
Although safety observations are still blinded (i.e. we do not know who received placebo and who 
received the drug), preliminary data did not show serious or severe adverse events nor any clinically 
concerning events from electrocardiograms, vital signs (blood pressure/heart rate, body temperature) 
and safety laboratory tests. At this time in point, reported adverse events after MMV553/placebo 
observed in these first 48 volunteers (i.e. with 5, 10, 20, 50, 100 and 160 mg) and considered as "drug-
related" are: mild transient elevation of total bile acids (blood tests changes, no symptoms), headache, 
palpitations and contact dermatitis. 
 
 


 
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2. Risks of Malaria Definitive Medication 
As previously indicated, all the study participants inoculated with malaria will receive a final treatment 
against malaria with a registered medication. This definitive medication will be given regardless of the 
efficacy profile of MMV533 observed in the study. 
For this specific study, the recommended first-line definitive medication is Malarone® (oral 
treatment). In case of intolerance or allergy to Malarone®, Riamet® (oral treatment) is the second-line 
medication. 
Risks associated with antimalarial drugs 
 
Malarone® is a registered, commercially available drug that is recognised as a treatment for 
malaria. It contains two drugs (atovaquone and proguanil hydrochloride) that work together to kill 
the malaria parasite. The dose of Malarone® that you will receive is the recommended standard 
daily dose of the drug. However, side effects from taking this antimalarial drug may occur. You may 
experience some side effects such as loss of appetite, nausea, vomiting, stomach pain, diarrhoea, 
mouth ulcers, rash or itching, headache, difficulty sleeping or strange dreams, dizziness, tiredness, 
cough, fever and elevated liver function tests. Most of these side effects have been mild and have 
not lasted very long. 
 
Riamet® is a registered, commercially available drug that is recognised as a treatment for malaria. 
It contains two drugs (artemether and lumefantrine) that work together to kill the malaria parasite. 
The dose of Riamet® that you will receive is the recommended standard daily dose of the drug. 
However, side effects from taking this antimalarial drug may occur. You may experience some side 
effects such as stomach pain, diarrhoea, dizziness, aching muscles/joints, sore throat/cough, 
nausea/vomiting, headache, difficulty sleeping, tingling, and fever/shivering. Most of these side 
effects have been mild and have not lasted very long. If you are administered MMV533 and later 
prescribed Riamet® as definitive medication for malaria in this study, additional electrocardiograms 
(ECG) will be performed on the last day of Riamet® treatment. The purpose of this ECG is to ensure 
that lumefantrine is not associated with an asymptomatic but clinically relevant change called “QTc 
prolongation”. If detected, further monitoring of this transient effect on your ECG might be 
requested. 
 
Primacin® is a registered and commercially available antimalarial drug containing primaquine 
phosphate, which is recognised as a treatment for the sexual gametocyte stage of malaria to 
prevent transmission to other humans (via Anopheles mosquito bite). Generally, side effects of 
Primacin® are few and the most common ones are abdominal cramps and pains, nausea, vomiting, 
dizziness, and headache. Effects on red blood cells may occur in susceptible individuals; a test will 
be done at screening to determine if you are at risk of this effect and to ensure your safety. 
 
If you are not able to take Riamet® and Malarone® for any reason (e.g., vomiting) then intravenous 
artesunate may be administered to you as a replacement. If this is required, you may be transferred 
to the hospital for treatment there. Intravenous artesunate is not a registered product in Australia. 
However, the World Health Organisation (WHO) recommend intravenous artesunate as the 
treatment of choice for adults with severe malaria. In the 401 participants in the challenge studies 
who have been inoculated with P. falciparum malaria (3D7 strain), only one participant has 
required intravenous artesunate treatment. 
 
The lists of side effects above are not complete. The study medications, like many medicines, can 
cause other side effects, some very severe or life-threatening, but rare. However, it is hard to 
predict if these side effects could occur in your case. Side effects may occur almost immediately 
after the drug is administered, or days later. Tell the clinical trial site doctor or nurse right away 
about any change in your health. 
 
You will be monitored closely during this study, so in the rare event that you experience a severe 
side-effect, you will receive rapid care at the study site or at the nearby Emergency Department at 
the Royal Brisbane and Women’s Hospital so that your safety is ensured. 


 
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 
The Consumer Medicines Information leaflets for Kodatef®, Riamet®, Malarone® and 
Primacin® containing the full list of side effects will be provided at your initial medical screening 
visit. Please read these leaflets for more details about these drugs. 
Possible allergic reactions 
It is important to understand that any medication, including the medication that you will be taking in 
this study, could possibly cause a serious life threatening or fatal allergic reaction. Allergic reactions 
may result in swelling of the face, lips, tongue, throat, and vocal cords, difficulty breathing, skin 
rashes, seizures, loss of consciousness, shock, and death may result from heart and lung failure in 
very rare cases. Any symptoms and signs of allergic reaction will be closely monitored. As a 
precaution, a management plan for possible allergic reactions has been developed by the study 
doctors. 
 
Blood Draw/Cannula Insertion Risks: 
During the study, you may have pain or bruising at the site where blood is drawn or a cannula (a 
temporary small plastic tube) is inserted. Insertion of the cannula or the drawing of blood may be 
associated with some pain. Possible side effects from blood drawing include feeling faint, 
inflammation of the vein, pain, bruising or bleeding at the site of puncture. These will normally 
disappear a few days after the procedure.  
Other blood collection risks include: 
1) there is a risk of a blood clot developing in the vein where the cannula was inserted. Usually 
this does not require any specific treatment. Rarely the clot can extend to a larger section of 
the vein or may even reach the deeper veins, in which case blood thinning (anticoagulant) 
medication may be recommended. 
2) there is a small risk of temporary damage (risk of permanent damage is very small) to the 
nerves next to where the IV site is inserted. 
3) there is a risk of developing an infection at the cannula site (rarely this could be serious) which 
may require antibiotics. 
Study staff will monitor the cannula site on a regular basis and if any concerns are noted the canula 
may be re-sited or removed.  
 
Blood Pressure Measurement Risks: 
There is no risk to your health when having your blood pressure tested. You may experience some 
feeling of discomfort as the cuff inflates and squeezes your arm, but it should only last a few seconds. 
Sometimes, there are tiny red spots that appear after the test just below the location of the cuff, they 
should be painless.  
 
Electrocardiogram (ECG) risks: 
The ECG test is a recording of the electrical activity of your heart. The sticky pads used may be cold 
when applied and sometimes cause some discomfort (irritation) such as redness or itching. If there is 
hair in the area where patches need to be applied, this area may need to be shaved in order to 
complete the ECG. Shaving may result in irritation. 
 
 
 


 
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Allergic Reaction Risks: 
There is a risk of allergic reaction. If you have a very serious allergic reaction, you may be at risk of 
death.  
 
In general, most symptoms are manageable and are mild to moderate in severity. But life-threatening 
reactions may occur at any drug dose. If you believe you are having a serious allergic reaction after 
you have been discharged, you should seek emergency medical assistance immediately by calling the 
emergency services on 000. 
 
Please notify the study doctor immediately if you experience any of these symptoms: 
 
Rash 
 
Wheezing and difficulty breathing 
 
Dizziness and fainting 
 
Swelling around the mouth, throat or eyes 
 
Fast pulse 
 
Sweating 
 
Abdominal pain 
 
Vomiting 
 
Diarrhoea 
 
You will be monitored very carefully for any signs or symptoms that you may be having an allergic 
reaction and appropriate care will be taken by the study doctor and nursing staff.  
If you do not understand what some of these side effects or risks mean, ask the study doctor or the 
study staff to explain them to you. 
 
Pregnancy Risk:  
The effects of MMV533 on the unborn child and on the newborn baby are not known at this stage of 
the development Because of this, it is important that research project participants are not pregnant 
or breast-feeding and do not become pregnant during the research study. You must not participate in 
the research if you are pregnant, or believe you may be pregnant, or trying to become pregnant, or 
breast-feeding. If you are female and child-bearing is a possibility, you will be required to undergo a 
pregnancy test prior to commencing the study. 
 
Female Participants 
Heterosexual women of childbearing potential (WOCBP) must agree to the use of a highly effective 
method of birth control (see below) combined with a barrier contraceptive from the screening visit 
until 60 days after the last dose of the study drug (covering a full menstrual cycle of 30 days starting 
after 5 half-lives of last dose of study drug) and have a negative result on urine pregnancy test 
performed before inoculation with the malaria challenge agent.  
Note:  
a) Highly effective birth control methods include: combined (oestrogen and progestogen containing) 
oral/intravaginal/transdermal/implantable hormonal contraception associated with inhibition of 
ovulation, progestogen-only oral/injectable/implantable hormonal contraception associated with 
inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal 
occlusion, vasectomised partner, or sexual abstinence or same sex relationship. 
b) Female participants who are abstinent (from penile-vaginal intercourse) must agree to start a 
double method if they start a sexual relationship with a male during the study. Female participants 
must not be planning in vitro fertilisation within the required contraception period.  


 
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Male Participants 
Males who have, or may have female sexual partners of child bearing potential during the course of 
the study must agree to use a double method of contraception including: 
- 
 condom plus diaphragm,  
- 
or condom plus intrauterine device,  
- 
or condom plus stable oral/transdermal/injectable/implantable hormonal contraceptive 
by the female partner, from the time of informed consent through to 90 days (covering a 
spermatogenesis cycle) after the last dose of the study drug. 
Abstinent males must agree to start a double method if they begin sexual relationship with a female 
during the study and up to 90 days after the last dose of study drug. Males with female partners of 
child-bearing potential that are surgically sterile, or males who have undergone sterilisation and have 
had testing to confirm the success of the sterilisation, will not be required to use above described 
methods of contraception. 
Please ask your study doctor if you have any questions regarding the forms of birth control that 
must be used while participating in this study. 
If you or your partner becomes pregnant during the study or up to 60 days (female participants) or 90 
days (female partners of male participants) after last dose of study drug, please tell your study doctor 
or staff immediately as we would like to request permission to follow this pregnancy and its outcome. 
The study doctor will also report the pregnancy to the Human Research Ethics Committee and to the 
study Sponsor.  
 
Allowing the pregnancy and outcome to be followed is optional. If you or your partner agrees to have 
this pregnancy followed, then she will be asked to sign a separate Pregnancy Follow-Up Participant 
Information and Consent Form. The information collected is similar to that which would be routinely 
collected during a typical pregnancy consultation. The consultation will be done in person at Q-Pharm 
Pty Ltd., and/or by telephone.  
 
In addition, she will be asked to notify the study doctor about the outcome of the pregnancy. If she 
forgets, she will be contacted to obtain this information. This outcome data collected includes: 
pregnancy complications and outcome, birth weight, birth defects (if any), and additional factors that 
may have had an impact on the outcome of the pregnancy (drugs, infections, family history etc.).  
 
The study doctor may also need to contact the obstetrician/gynaecologist of you or your partner. 
 
10. 
What will happen to my test samples? 
The blood and urine samples collected for the assessment of your health status (e.g. liver and kidney 
function tests), G6PD status and red blood cells antibodies will be processed by a local pathology 
laboratory. These samples will be labelled with your unique study participant number, your initials 
and date of birth, and will not be provided to anyone outside the study site and the pathology 
laboratory. These samples will be destroyed following analysis. 
 
Blood samples collected for pharmacokinetics and pharmacodynamics analysis will be sent to various 
Sponsor-approved laboratories in Switzerland. These samples will be labelled with your unique study 
participant number and will not contain any information that can identify you personally. These 
samples will be stored during the study at a secure premise and the samples will be destroyed 
following analysis at the end of the study. 
 


 
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Serum Safety samples collected for safety assessments related to the study drug will be stored at 
Nucleus Network. If the sample is not used, it will be destroyed at the end of the study. Serum Safety 
samples collected for safety assessments related to the malaria challenge agent will be retained for 
at least 15 years from the completion of the study at the QIMR Berghofer Institute. 
Parasite drug resistance samples may be shipped to a national or international reference laboratory 
for phenotypic assessment and parasite gene sequencing analysis 
 
11. 
What if new information arises during this research study? 
Sometimes during a research study, new information becomes available about the treatment that is 
being studied. If this happens, your study doctor will tell you about it and discuss with you whether 
you want to continue in the research study. If you decide to continue in the research study, you will 
be asked to sign an updated consent form. 
 
Also, on receiving new information, your study doctor might consider it to be in your best interests to 
withdraw you from the research study. If this happens, he/she will explain the reasons and arrange 
for your regular health care to continue. 
Sometimes this information becomes available after you have completed the study. If the Investigator 
and Sponsor believe it to be relevant for your health, you may be contacted by Q-Pharm Pty Ltd., even 
beyond the end of the study. 
 
12. 
Can I have other treatments during this research study? 
The proposed study implies that you will receive two types of drugs as part of the research after 
malaria inoculation: the drug under development for treatment of acute uncomplicated malaria 
(MMV533, single dose) and a full treatment with a registered antimalarial (Malarone® oral treatment 
as first-line definitive medication) to ensure that remaining parasites in your body are fully eliminated. 
Whilst you are participating in this research study, you are not able to take any medications or 
treatments other than those agreed upon at the start of your participation in the study, unless 
medically required. It is important to tell your study doctor and the study staff, at each clinic visit, 
about any treatments or medications you may have taken, including over-the-counter medications, 
vitamins or herbal remedies, acupuncture or other alternative treatments. 
Sometimes it is necessary for you to receive treatment for a medical problem whilst on study (e.g. an 
infection). It is preferable, where possible, to discuss this with the study doctor, including by phone or 
additional follow up visits.  
 
13. 
What if I withdraw from this research study? 
If you decide to withdraw from the study, please notify your study doctor or staff before you withdraw. 
This notice will allow the study doctor to discuss any health risks or special requirements linked to 
withdrawing. 
If you do withdraw your consent during the research study, any information collected on you up to 
the point of withdrawal will be used.  
 
Data collected after your withdrawal, if any, may be used: 
 
If you have any on-going medical issues at the time of the withdrawal, we would like the 
option to continue to follow you until its resolution. If you do not agree to participate in follow 
up visits at the study centre, we can provide a referral letter for your GP to provide follow-up 
and treatment if necessary. You may also contact your study doctor if you experience a new 
adverse event. 


 
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 
If you do withdraw your consent during the research project, the study doctor and relevant 
study staff will not collect additional personal information from you, although personal 
information already collected will be retained to ensure that the results of the research 
project can be measured properly and to comply with law. You should be aware that data 
collected by the sponsor up to the time you withdraw will form part of the research project 
results. If you do not want them to do this, you must tell them before you join the research 
project 
Biological Samples collected prior to your withdrawal: 
 
If you withdraw your consent, all your biological sample(s) already sent to sponsor approved 
laboratories will be used for analysis. You should be aware that your biological samples 
collected by the sponsor up to the time you withdraw will form part of the research project 
results. This is to ensure that the results can be measured properly. If you do not want them 
to do this, you must tell them before you join the research project. 
 
14. 
Could this research be stopped unexpectedly? 
This research study or your participation in the study may be stopped unexpectedly for the reasons 
listed below.   
 
Unacceptable side effects 
 
The drug being shown not to be safe 
 
Decisions made in the commercial interests of the sponsor or by local regulatory/health 
authorities 
 
If you don’t follow the instructions of the clinical unit staff; or 
 
If the study doctor decides it is in the best interest of your health and welfare to stop. 
 
15. 
What will happen when the research study ends? 
The study data will be analysed, and a final report provided to the study doctor, who will share the 
results with you when requested. The disclosure and/or any published results will be available to you 
when requested. It is usual for a number of years to elapse before definitive results of this type of 
study are available. These may be published in medical journals that are available to the public. You 
should feel free to ask the study staff about this. 
 
Part 2 - How is this study being conducted? 
 
16. 
What will happen to information about me? 
Any information and data obtained/retained in connection with this research study that can identify 
you will remain confidential and will only be used for this research study and future research related 
to the pathophysiology of malaria and/or mechanism of action of the drug (MMV533) under 
evaluation. 
 
Information about you may be obtained from your health records held at other health services for the 
purpose of this research. By signing the consent form you agree to the study team, including Sponsor 


 
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delegates, accessing health records if they are relevant to your participation in this research study to 
ensure data accuracy. Whilst every effort will be made to keep your personal information confidential, 
the data gathered for this study will also be reviewed by a Sponsor delegate. This delegate will have 
access to your medical records, without violating your confidentiality to the extent permitted by local 
laws and regulations, to verify the data are correct and complete. 
 
The data collected as part of this research study may be reviewed by representatives of the 
international sponsor, MMV, its affiliated companies and/or subcontractors, the local sponsor, 
Southern Star Research (SSR), the Alfred Hospital Ethics Committee, by authorised representatives of 
the Australian Therapeutic Goods Administration or other regulatory agencies. Information may be 
transferred to parties in countries (and regions) other than Australia including the US, and Europe for 
these purposes. Southern Star Research (SSR), MMV representatives, collaborators and contracted 
agencies comply with internal procedures to protect personal information even in countries whose 
data privacy laws are less strict than those of this country. In all cases when dealing with your personal 
(coded) information. MMV, and any of their agents will comply with the Privacy Act 1988. If you have 
any concerns on how your information is handled, please feel free to ask a member of the study team 
for more information. 
 
By signing the consent section, you authorise release of, or access to, this confidential information to 
the relevant study personnel and regulatory authorities as noted above. 
 
Study Medical Records 
Data from your study medical record will be identifiable and stored in secured offices at Q-Pharm Pty 
Ltd. Only research team members and authorised representatives from the Sponsor, the Ethics 
Committee or regulatory agencies will have access to your medical records. 
 
In accordance with relevant Australian and/or Queensland privacy and other relevant laws, you have 
the right to request access to your information collected and stored by the research team. You also 
have the right to request that any information with which you disagree be corrected. Please contact 
the study team member named at the end of this document if you would like to access your 
information. 
Information about your participation in this research study will be recorded in your study records at 
Q-Pharm Pty Ltd.  
 
 
Case Report Form (CRF) 
Information you provide us will be recorded in electronic case report forms (CRF).  Your information 
will be coded by your unique study number, your gender and birth date only and thus will be 
considered re-identifiable. The recorded data will be kept in an electronic database which will be 
managed throughout the study by Southern Star Research (SSR). Information from these CRFs will 
form part of the study results, which may be published. This data base will form part of the study 
results, which may be published.   
 
A copy of the database entries and your medical record will be kept securely in accordance with ICH 
GCP requirements with all other study related documents. 
 
This information will be reviewed by authorised individuals from the contract research organisation, 
MMV or affiliates, contractors and/or Health Authorities or Government Agencies (including the 
Therapeutic Goods Administration, as well as health authorities in USA and other countries) and 
delegates of the Ethics Committee for confirming the accuracy of the research study data.  
 


 
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By signing the consent section, you authorise release of, or access to, this confidential information to 
the relevant study personnel and regulatory authorities as noted above. 
 
Publications 
A report of the study results may be submitted for publication. In any publication and/or presentation, 
information will be provided in such a way that you cannot be identified, except with your permission. 
If you want to know more about Q-Pharm Pty Ltd. approach to privacy or access any of your 
information 
held 
by 
Q-Pharm 
Pty 
Ltd., 
you 
can 
contact 
the 
privacy 
officer 
at 
privacyofficer@nucleusnetwork.com.au.  
 
17. 
Complaints and compensation 
If you suffer any injuries or complications because of this research study, you should contact the 
study doctor or study team as soon as possible and you will be assisted with arranging appropriate 
medical treatment. If you are eligible for Medicare, you can receive any medical treatment required 
to treat the injury or complication, free of charge, as a public patient in any Australian public 
hospital.  
 
If you are not eligible for Medicare, the Sponsor and/or the Q-Pharm Pty Ltd. (Nucleus Network Pty 
Ltd) will cover the cost of any and all health care service costs incurred by you in respect of any 
injury or complication that has been independently determined to have been incurred as a result of 
the study drug or study procedure. 
 
There are two avenues that may be available to you for seeking compensation if you suffer an injury 
because of your participation in this research study: 
 
The pharmaceutical industry has set up a compensation process, with which the local sponsor 
of this research study, Southern Star Research (SSR), has agreed to comply. Details of this 
process and conditions are set out in the Medicines Australia Guidelines for Compensation for 
Injury Resulting from Participation in a Company-Sponsored Clinical Trial. In accordance with 
these Guidelines, the sponsor will determine whether to pay compensation to you, and if so, 
how much. The research staff can give you a copy of the Guidelines together with this 
Participant Information and Consent Form or it can be accessed online; 
 
https://medicinesaustralia.com.au/wp-content/uploads/sites/52/2010/09/Clnical-Trials-
Compensation-Guidelines-1.pdf. If you have any questions about the Guidelines, please 
contact Paul Griffin on p.griffin@nucleusnetwork.com.au. 
 
You may be able to seek compensation through the courts. 
If you are not satisfied with how your personal information has been handled (as laid out in the Privacy 
Act, 1988), then you can make a complaint to the Office of the Australian Information Commissioner 
(OAIC). It is free to lodge a complaint and you do not need a lawyer, however if you do decide to hire 
a lawyer, you must pay for the lawyer yourself. You can choose to withdraw your complaint at any 
time. Please refer to http://www.oaic.gov.au/privacy/privacy-complaints for more information. 
 
18 
Who is organising and funding the research? 
This research is being conducted by Medicines for Malaria Venture (MMV) based in Geneva and 
sponsored in Australia by Southern Star Research. MMV may benefit financially from this research 
study if, for example, the study assists to obtain approval for a new drug. 


 
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By taking part in this research study you agree that samples of your blood (or data generated from 
analysis of these materials) may be provided to MMV. 
MMV may directly or indirectly benefit financially from your samples or from knowledge acquired 
through analysis of your samples. 
If knowledge acquired through this research leads to discoveries that are of commercial value to MMV, 
the study doctor or their institutions, there will be no financial benefit to you or your family from these 
discoveries. 
MMV, other researchers, or research companies may patent or sell discoveries that result from this 
research. Neither MMV nor the study doctor will compensate you if this happens. 
Contractors engaged by MMV will receive a payment from MMV for undertaking this research study. 
No member of the research team will receive a personal financial benefit from your involvement in 
this research study (other than their ordinary wages). 
 
19. 
Will I be reimbursed to take part in this research study? 
 
If you are eligible and enrolled in the study, you will be reimbursed $150.00 for the screening and 
follow-up visits, at a daily rate of $480.00 per day for the in-clinic stay part of this study, and $50.00 
for each follow-up phone call. Please note that admission and discharge days will be reimbursed at 
half-day rates. For this study, you may be required to attend additional follow-up visits at the 
discretion of the study doctor, so we ask you to be readily contactable and available to attend visits at 
any time as required throughout the study period. We recognise that this is an increased level of 
commitment compared to other studies, so you will be reimbursed $55.00 per day from Day -7 to Day 
28 (except during the in-clinic stay, in total $1650 for the increase level of commitment) as 
compensation for your availability and flexibility. You will also be reimbursed $150.00 for each follow-
up visit you attend, including any additional visits required by the study doctor. 
 
The total reimbursement for participants who complete the entire study will be approximately 
$6,450.00, depending on the number of outpatient visits attended. This reimbursement rate includes 
compensation for your time, travel expenses, parking and inconvenience across the entire study 
period. 
 
If you are an alternate, and do not get dosed, you will receive a partial reimbursement of $450.00. 
 
 
If you are deemed to be ineligible after your screening visit due to a medical result that is independent 
from your direct actions, you will be reimbursed $150.00 for your screening visit. This payment will be 
made within a month of your screening appointment. Screening visit will not be reimbursed if your 
ineligibility is due to a positive drug of abuse or alcohol testing. 
 
Regardless of whether you withdraw early or complete the study, you will be reimbursed within 10 
business days of the end of study visit via electronic funds transfer directly into your bank account. 
Should you withdraw from the study before the final visit you will receive a partial reimbursement 
according to the number of visits you have attended.  
 
Reimbursement compensates for your time, travel expenses, parking and inconvenience. This 
reimbursement is not made for undergoing risk nor is it to compensate you for any loss of earnings as 
a result of your participation.   
 
It is not anticipated that participation in this research study will result in any additional cost to you.  
 


 
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20. 
Who has reviewed the research study? 
All research in Australia involving humans is reviewed by an independent group of people called a 
Human Research Ethics Committee (HREC) who make sure that the rights, safety and well-being of 
participants in a study are protected. The ethical aspects of this research study have been approved 
by the Alfred Hospital Ethics Committee. 
 
This study will be carried out according to the National Statement on Ethical Conduct in Human 
Research (March 2007) produced by the National Health and Medical Research Council of Australia. 
This statement has been developed to protect the interests of people who agree to participate in 
human research studies. 
 
21. 
Further information and who to contact 
The person you may need to contact will depend on the nature of your query. If you want any 
further information concerning this study, please contact the below; 
General Enquiries:  
 
(07) 3707 2700 
After hours contact:  
 
0451 515 440 (urgent medical enquiries only) 
 
If you have any medical questions/problems which may be related to your involvement in the study 
(for example, any side effects), you can contact the principal study doctor (Dr Paul Griffin on 
p.griffin@nucleusnetwork.com.au. Please also refer to your participant card with your study specific 
contact numbers.  
For matters relating to research at the site at which you are participating, the details of the local site 
complaints person are: 
Complaints contact person 
Position 
Complaints Officer 
Email 
complaintsofficer@nucleusnetwork.com.au  
Privacy contact person 
Position 
Privacy Officer 
Email 
privacyofficer@nucleusnetwork.com.au  
 
If you have any complaints about any aspect of the study, the way it is being conducted or any 
questions about being a research participant in general, then you may contact: 
Reviewing HREC approving this research and HREC Executive Officer details 
 
Please reference the following Alfred project number: 125/21 
 
Reviewing HREC name 
Alfred Hospital Ethics Committee 
Position 
Governance Officer, Ethics and Research Governance, Alfred Health 
Telephone 
(03) 9076 3619  
Email 
research@alfred.org.au  


 
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Page 30 of 32 
Document No. SPFMA001-03 
Implementation Date: 22-May-2020 
 
CONSENT 
Alfred Project Number
125/21
Full Study Title: 
A Phase 1b study to assess the safety, tolerability and antimalarial 
activity of MMV533 against Plasmodium falciparum 3D7 blood stage 
infection in healthy volunteers. 
Protocol Number:
MMV_MMV533_20_01
Test Drug Code:
MMV533
International Sponsor:
Medicines for Malaria Venture (MMV)
Local Sponsor:
Southern Star Research Pty Ltd (SSR)
Coordinating Principal 
Investigator: 
Dr Paul Griffin 
Principal Investigator:
Dr Paul Griffin
Location: 
Q-Pharm Pty Ltd, Level 5 Clive Berghofer Cancer Research Centre, 
(CBCRC) 300C Herston Rd, Herston QLD, 4006  
 
 I have read the Participant Information Sheet, or someone has read it to me in a language that 
I understand. 
 I have had an opportunity to ask questions and I am satisfied with the answers I have received. 
 I understand the purposes, procedures and risks of the research described for this study. 
 I give permission for my doctors, other health professionals, hospitals or laboratories outside 
this hospital to release information to Q-Pharm Pty Ltd. for the purposes of this study. I 
understand that such information will remain confidential.  
 I freely agree to participate in this research study as described and understand that I am free 
to withdraw at any stage during the study without affecting my future health care 
 I understand that I will be given a signed copy of this document to keep. 
 


 
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Document No. SPFMA001-03 
Implementation Date: 22-May-2020 
 
Participant’s First Name (printed)  
…………………Middle Initial..……Surname………………. 
Signature
 
Date
_____/______/________ 
Time _____:_____ 
Declaration by Study Doctor/Senior Researcher 
I have given a verbal explanation of the research study; its procedures and risks and I believe that the 
participant has understood that explanation. 
Study Doctor/Researcher’s First 
Name (printed) ……….…………Middle Initial……..Surname…………….. 
Signature
 
Date
_____/______/________ 
Time _____:_____ 
A senior member of the research team must provide the explanation of, and information concerning, 
the research study. 
Note: All parties signing the consent section must date their own signature. 


 
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Document No. SPFMA001-03 
Implementation Date: 22-May-2020 
 
 
 
 
 
FORM FOR WITHDRAWAL OF PARTICIPATION 
 
Alfred Project Number
125/21
Full Study Title: 
A Phase 1b study to assess the safety, tolerability and antimalarial 
activity of MMV533 against Plasmodium falciparum 3D7 blood stage 
infection in healthy volunteers. 
Protocol Number:
MMV_MMV533_20_01
Test Drug Code:
MMV533
International Sponsor:
Medicines for Malaria Venture (MMV)
Local Sponsor:
Southern Star Research Pty Ltd (SSR)
Coordinating Principal 
Investigator: 
Dr Paul Griffin 
Principal Investigator:
Dr Paul Griffin
Location: 
Q-Pharm Pty Ltd, Level 5 Clive Berghofer Cancer Research Centre, 
(CBCRC) 300C Herston Rd, Herston QLD, 4006  
 
Declaration by Participant
I wish to withdraw from participation in the above research study and understand that such 
withdrawal will not affect my routine treatment, my relationship with those treating me or my 
relationship with Q-Pharm Pty Ltd. 
Participant’s First Name 
(printed) ………………Middle Initial…..…Surname….…………....... 
Signature
 
Date
_____/______/________ 
Time
_____:_____ 
Study Doctor to include a description of the circumstances for withdrawal, if provided by the 
participant. 
 
Declaration by Study Doctor 
I have given a verbal explanation of the implications of withdrawal from the research study and I 
believe that the participant has understood that explanation. 
Study Doctor/Researcher’s 
First Name (printed) ……………Middle Initial……..Surname….…………....... 
Signature
 
Date
_____/______/________
Time
_____:_____ 
Note: All parties signing the consent section must date their own signature. 

Prot_000.pdf: 
Medicines for Malaria Venture 
 
Version 1.0  
Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 1 of 96 
 
 
CLINICAL STUDY PROTOCOL  
A Phase 1b study to assess the antimalarial activity of 
MMV533 against Plasmodium falciparum 3D7 blood stage 
infection in healthy volunteers.  
 
Protocol Number: 
MMV_MMV533_20_01 
Investigational Product: 
MMV533 for oral administration 
Principal Investigator: 
Dr Paul Griffin 
Q-Pharm Pty Ltd 
Level 5, 300C Herston Rd 
Herston Qld 4006, Australia 
Tel: +61 (0)7 3845 3636 
Local Sponsor/CRO: 
Southern Star Research Pty Ltd (SSR) 
1 Merriwa St 
Gordon, NSW 2072 
Australia 
Tel: +61 (0)2 9011 6266 
Global Sponsor: 
Medicines for Malaria Venture (MMV) 
ICC-Block G 3rd Floor 
20 route de Pré-Bois 
1215 Geneva 15 
Switzerland 
Tel: +41 22 555 03 00 
Sponsor Signatories: 
Dr Stephan Chalon, Medical Director 
Dr Amina Haouala, Clinical Science Lead 
Trial Medical Monitor: 
Dr Joanne Marjason 
Southern Star Research Pty Ltd 
Tel: +61 (0)427 959 156 
Date and Version: 
V1.0 01 March 2021 
Confidentiality Statement 
This document contains the confidential information of Medicines for Malaria Venture.  
It is provided to you as an Investigator or consultant for review by you, your personnel, 
and the applicable Human Research Ethics Committee (HREC).  Your acceptance of this 
document constitutes an agreement that you will not disclose the information contained 
herein to others without the prior written consent of Medicines for Malaria Venture, unless 
it is necessary to obtain informed consent from potential study volunteers.  No other use 
or reproduction is authorized by Medicines for Malaria Venture, nor does Medicines for 
Malaria Venture assume any responsibility for unauthorized use of this protocol. 
 
 


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1 PROTOCOL SUMMARY 
1.1 
PROTOCOL SYNOPSIS 
Protocol Title 
A Phase 1b study to assess MMV533 antimalarial activity 
against Plasmodium falciparum 3D7 blood stage infection in 
healthy volunteers. 
IND Number 
n/a 
Protocol Number 
MMV_MMV533_20_01 
Local Sponsor 
Southern Star Research Pty Ltd (SSR) 
Global Sponsor 
Medicines for Malaria Venture (MMV) 
Principal Investigator 
Dr Paul Griffin, Q-Pharm Pty Ltd  
Phase of Development 
Phase 1 
Number of Study Sites 
One Phase 1 clinical trial unit site will be conducting the study.  
Treatment Groups 
MMV533 (single, oral dose). 8 volunteers per cohort for 1-3 
cohorts (8-24 volunteers total).  
Volunteer Population 
Healthy malaria-naïve adult volunteers 
Investigational 
Medicinal Product 
(IMP) 
MMV533, single dose taken orally (5 mg or 50 mg tablets) with 
240 mL water under fasting conditions  
Doses:  
Starting dose: 20 mg as single oral dose in cohort 1A (4  
participants).  
The MMV533 dose to be tested in the subsequent cohorts will be 
selected based on PK, PD and safety data from the preceding 
cohort and PK and safety data from the First-in-Human (FIH) 
study. Cohort 1B (4 volunteers) dose will be no more than 50 mg. 
Subsequent doses will not exceed a dose tested and deemed to be 
safe in the FIH study and will not exceed 200 mg MMV533. 
Additional Study 
Treatment/Intervention: 
Malaria Challenge 
Agent 
Non-IMP 
Malaria challenge agent for Induced Blood Stage Malaria (IBSM) 
model. Volunteers will be inoculated intravenously with a single 
dose of  approximately 2,800 viable human erythrocytes infected 
with Plasmodium falciparum 3D7 in saline for injection. The total 
volume of the inoculum will be approximately 2 mL.  
Additional Study 
Treatment: Malaria 
Rescue Medication 
Non-IMP 
Mandatory Rescue Medication:  
• 
Artemether/lumefantrine (20 mg/120 mg; Riamet®). 6 oral 
doses of 4 tablets each at 0, 8, 24, 36, 48 and 60 hours (total 
24 tablets), taken 240 mL full-fat milk.   
• 
Primaquine phosphate (equivalent 45 mg primaquine; 
Primacin™). One oral dose of 6 tablets (each with 13.2 mg 
primaquine phosphate, equivalent to 7.5 mg primaquine) 


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taken with food; for volunteers with mild G6PD deficiency, 
2 tablets taken orally as single dose with food (total dose 
15 mg).  Taken additionally to Riamet® or Malarone® at the 
discretion of the Investigator if required to ensure complete 
clearance of gametocytes.  
• 
Atovaquone/proguanil 
hydrochloride 
(250 mg/100 mg; 
Malarone®), only if volunteer has an intolerance to Riamet® 
(e.g. allergy), or contraindication to Riamet® develops or is 
suspected. Three-day course of 4 tablets taken once daily 
orally with food or milky drink.  
• 
Artesunate may be used if volunteers unable to tolerate oral 
antimalarial rescue treatment (eg, vomiting). Intravenous 
administration of 2.4 mg/kg at 0, 12, 24, 48 hours and then 
daily for up to 7 days or until able to take oral drugs.   
Duration of Study per 
Volunteer 
Screening 28 days prior to inoculation (Day -36 to Day -9), 
Inoculation and subsequent monitoring 8 days (Day -8 to Day -1), 
Confinement, Treatment and observation period 5 days (Day -1 to 
Day 5), follow-up including rescue treatment of 23 days until EOS 
(Day 5 to Day 28±3). Total study duration: up to 10 weeks from 
Screening until EOS.   
Objectives 
To assess in healthy adult volunteers: 
Primary: 
• 
To characterize the activity of single oral doses of MMV533 
on clearance of Plasmodium falciparum 3D7 blood stage 
parasites from the blood in an IBSM model 
Secondary: 
• 
To characterize the safety and tolerability of single oral doses 
of MMV533 administered after IBSM challenge 
• 
To characterize the pharmacokinetic parameters of single 
oral doses of MMV533 after IBSM challenge 
• 
To determine the relationship between MMV533 PK and 
asexual blood-stage parasitaemia in an IBSM model 
Exploratory: 
• 
To investigate drug resistance of P. falciparum 3D7 after 
MMV533 administration 
Endpoints 
Primary endpoints:  
• Parasite reduction ratio over 48 hours (PRR48) 
• Parasite clearance half-life (Pt½) 
• Lag phase 
• Number of volunteers whose parasitaemia levels fall 
below limit of quantification (LOQ) following 
treatment with IMP 
• Number of volunteers with recrudescence of asexual 
parasitemia, defined as ≥5,000 blood stage parasites/mL 
after initial parasite clearance accompanied by either a 
two-fold parasitaemia increase within 48 hours, or re-


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occurrence of malaria symptoms with a malaria clinical 
score ≥6. 
• Time to recrudescence defined as the time at which 
asexual parasite levels reoccur after being below the 
LOQ or the time for which asexual parasitaemia levels 
are minimum, or, if not defined, the last observed time 
point without recrudescence. 
Secondary endpoints: 
Safety 
• Assessment of AEs/TEAEs; two phases will be defined: 
one corresponding to the inoculation phase (ie, 8 days 
before IMP administration), and one corresponding to 
treatment phase (i.e. 28 days after IMP administration) 
• Clinical laboratory evaluations including haematology, 
biochemistry, coagulation, urinalysis. 
• Vital signs (body temperature, blood pressure and heart 
rate supine), 
• 12-lead ECG (automatic reading): RR, HR, PR, QRS, 
QT, QTc measured by on site-device. 
Pharmacokinetics of MMV533: 
• Plasma parameters: at least Cmax, tmax,  AUClast, AUC, 
t½, CL/F, Vss/F, Vz/F, plasma ratios of Cmax, AUClast and 
AUC 
Pharmacokinetics-Pharmacodynamics: 
• The PK/PD relationship between MMV533 plasma 
concentrations and blood stage asexual parasitaemia 
will be determined  
• Other key parameters will be derived from the PKPD 
model including minimum inhibitory concentration 
(MIC), 
the 
minimal 
parasiticidal 
concentration 
(MPC90), and the parasite reduction rate in 48 h 
(PRR48). 
Exploratory endpoints: 
• Perform in vitro drug sensitivity testing determining the 
50% inhibitory concentrations (IC50) and the 
percentage surviving parasites 
Study Description 
The study will characterise the effects of single oral doses of 
MMV533 on the clearance of Plasmodium falciparum 3D7 using 
the IBSM model. This is a well-established method for obtaining 
useful pharmacokinetic-pharmacodynamic (PK-PD) information 
on anti-malarial drugs.  
The study will be an open-label, pilot Volunteer Infection Study 
(VIS) using the IBSM model, single dose IMP, conducted in 
healthy malaria-naive adult volunteers infected with Plasmodium 
falciparum 3D7, up to 3 cohorts (n=8 per cohort receiving active 


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treatment) enrolled in a sequential manner. Volunteers will be 
enrolled within a 28 day screening period to ensure volunteers 
meet all the inclusion criteria and none of the exclusion criteria.  
On Day -8 (8 days prior to IMP administration), volunteers will 
attend the clinical unit to be inoculated with the malaria challenge 
agent containing approximately 2,800 viable human erythrocytes 
infected with P. falciparum 3D7 parasites. Parasitaemia will be 
monitored on an outpatient basis daily on Day -4, and then twice 
daily on Day -3, Day -2 and until admission to the clinical unit on 
Day -1 for eligibility check and confinement.  
Volunteers will be administered IMP on Day 1 and will have 
safety monitoring and blood sampling for parasitaemia monitoring 
and PK analysis on an inpatient basis for at least 108 hours post-
IMP administration. Volunteers will be discharged from the 
clinical unit after review of ECG, vital signs, clinical and 
laboratory tests safety data by the Principal Investigator or 
delegate, and will then attend the clinical unit on an outpatient 
basis regularly for continued safety monitoring and blood 
sampling for parasitaemia monitoring and PK analysis.  
Volunteers will be administered mandatory malaria rescue 
medication at Day 21±3, or earlier if there is failure to clear 
parasites or recrudescence and at the discretion of the Principal 
Investigator or delegate. EOS will be on Day 28±3. Volunteers 
must have had at least two negative 18S qPCR results prior to EOS 
and must have completed their course of anti-malarial rescue 
medication. 
In the event of recrudescence, blood samples will be collected 
prior to rescue treatment to culture parasites for drug resistance 
testing. 
Sample Size 
Up to 24 volunteers inoculated, randomized and dosed (8 
volunteers per group all receiving MMV533) 
Inclusion Criteria 
Volunteers must fulfil all the following inclusion criteria to be 
eligible to participate in the study: 
1. Having given written informed consent prior to undertaking 
any study-related procedure. 
2. Male or female aged between 18 to 55 years inclusive.  
3. Available for the duration of the study and for 2 weeks 
following the End of Study Visit (EOS). 
4. Lives with a spouse, family member, or housemate from the 
time of inoculation with the malaria challenge agent through 
to the EOS. 
5. Total body weight greater than or equal to 50 kg, and a body 
mass index (BMI) within the range of 18 to 32 kg/m2 
(inclusive). 
6. Willing to defer blood donations to a blood service for a 
minimum of 6 months after the EOS. 


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7. Heterosexual women of childbearing potential (WOCBP) 
must agree to the use of a highly effective method of birth 
control (see below) combined with a barrier contraceptive 
from the screening visit until 30 days after the last dose of 
the IMP (covering a full menstrual cycle of 30 days starting 
after 5 half-lives of last dose of IMP) and have a negative 
result on urine pregnancy test performed before inoculation 
with the malaria challenge agent.  
Note:  
a. Highly effective birth control methods include: combined 
(oestrogen 
and 
progestogen 
containing) 
oral/intravaginal/transdermal/implantable 
hormonal 
contraception associated with inhibition of ovulation, 
progestogen-only oral/injectable/implantable hormonal 
contraception associated with inhibition of ovulation, 
intrauterine device, intrauterine hormone-releasing 
system, bilateral tubal occlusion, vasectomised partner, 
or sexual abstinence or same sex relationship. 
b. Female volunteers who are abstinent (from penile-
vaginal intercourse) must agree to start a double method 
if they start a sexual relationship with a male during the 
study. Female volunteers must not be planning in vitro 
fertilisation within the required contraception period.  
8. Women of non-childbearing potential (WONCBP) are 
defined as: 
a. Natural (spontaneous) post-menopausal defined as 
being amenorrhoeic for at least 12 months without an 
alternative medical cause with a screening follicle 
stimulating hormone level (FSH) >25 IU/L (or at the 
local laboratory levels for post-menopause) 
b. Premenopausal with irreversible surgical sterilization 
by hysterectomy and/or bilateral oophorectomy or 
salpingectomy at least 6 months before screening (as 
determined by volunteer medical history) 
9. Males who have, or may have female sexual partners of child 
bearing potential during the course of the study must agree 
to use a double method of contraception including condom 
plus diaphragm, or condom plus intrauterine device, or 
condom plus stable oral/transdermal/injectable/implantable 
hormonal contraceptive by the female partner, from the time 
of informed consent through to 60 days (covering a 
spermatogenesis cycle) after the last dose of the IMP. 
Abstinent males must agree to start a double method if they 
begin sexual relationship with a female during the study and 
up to 60 days after the last dose of study drug. Males with 
female partners of child-bearing potential that are surgically 
sterile, or males who have undergone sterilisation and have 
had testing to confirm the success of the sterilisation, may 


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also be included and will not be required to use above 
described methods of contraception. 
10. Vital signs after 5 minutes resting in supine position: 
a. Systolic blood pressure (SBP) - 90–140 mmHg, 
b. Diastolic blood pressure (DBP) - 40–90 mmHg, 
c. Heart rate (HR) 40–100 bpm. 
11. At Screening and pre-inoculation with the malaria 
challenge agent: normal standard mean of triplicate 12-lead 
electrocardiogram (ECG) parameters after 10 minutes 
resting in supine position in the following ranges:  
a. QT ≤ 500 msec,  
b. QTcF ≤ 450 msec, QTcB ≤ 450 msec,   
c. PR interval ≤ 210 msec for both males and females, and  
d. Normal ECG tracing unless the Principal Investigator or 
delegate considers an ECG tracing abnormality to be not 
clinically relevant.  
12. In the opinion of the Principal Investigator or delegate, the 
individual has a high probability of adherence with and 
completion of the study, and willing and able to withdraw 
and refrain from restricted medications. 
13. Certified as healthy by a comprehensive clinical assessment 
(detailed 
medical 
history 
and 
complete 
physical 
examination). 
14. Fluent in English and able to understand and comply with 
written and verbal protocol-related requirements. 
15. Agrees to adhere to the lifestyle considerations throughout 
the study (see Section 4.3.3) and is willing to consume 
240 mL full-fat milk with each dose of rescue medication 
Riamet®.  
Exclusion Criteria 
If any of the following exclusion criteria apply, the potential 
volunteer will not be permitted to participate in the study: 
1. Any lifetime history of malaria or participation in a previous 
malaria challenge study or malaria vaccine trial.  
2. Must not have had malaria exposure that is considered 
significant by the Principal Investigator or delegate. This 
includes but is not limited to:  
- history of having travelled to or lived (> 2 weeks) in a 
malaria-endemic region during the past 12 months or 
planned travel to a malaria-endemic region during the 
course of the trial;  
- history of having lived for >1 year in a malaria-endemic 
region in the past 10 years;  
- history of having ever lived in a malaria-endemic region for 
more than 10 years inclusive. For endemic regions see 
https://malariaatlas.org/explorer/#/ Bali is not considered a 
malaria-endemic region. 


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3. Presence of acute infectious disease and/or abnormal body 
temperature (defined as an a.m. tympanic temperature 
>37.5 ºC or a p.m. >37.7 ºC) at pre-inoculation.. 
4. Haematology, biochemistry or urinalysis results that are 
outside of the laboratory normal reference ranges AND are 
either: 
- considered clinically significant by the Principal Investigator 
or delegate; OR  
- considered not clinically significant by the Principal 
Investigator or delegate BUT ARE ALSO outside of 
Sponsor-approved clinically acceptable laboratory ranges 
(Appendix 1) 
NOTE: Volunteers are not excluded if abnormal/out of 
laboratory normal reference range results are considered not 
clinically significant by the Principal Investigator or delegate 
AND are within the ranges specified in Appendix 1. 
5. Breastfeeding or lactating; positive serum pregnancy test at 
screening, positive urine pregnancy test upon admission or at 
other timepoints as specified by schedule of activities tables.  
6. Has previously received a blood transfusion  
7. Use of antibiotics within 6 weeks of Screening.  
8. Use of systemic therapies with antimalarial activity within 6 
weeks of Screening. This includes (but not limited to) 
artemisinin, 
amodiaquine, 
atovaquone, 
chloroquine, 
mefloquine, mepacrine, primaquine, proguanil, quinine, 
sulfadoxine-pyrimethamine, benzodiazepine, flunarizine, 
fluoxetine, 
tetracycline, 
azithromycin, 
clindamycin, 
doxycycline, and tafenoquine.  
9. Prior to screening and inoculation with the malaria challenge 
agent:  
• any systemic administration (oral, pulmonary/nasal, 
IV) of corticosteroids, anti-inflammatory drugs 
(excluding commonly used over-the-counter anti-
inflammatory drugs such as ibuprofen, acetylsalicylic 
acid, 
diclofenac), 
immunomodulators 
or 
anticoagulants within the past three months. 
• Ibuprofen (preferred) may be used at doses of up to 
1.2 g/day, or paracetamol at doses of up to 2 g/day 
after discussion with the Investigator. Limited use of 
other 
non-prescription 
medications 
or 
dietary 
supplements, not believed to affect subject safety or 
the overall results of the study, may be permitted on a 
case-by-case basis following approval by the Sponsor 
in consultation with the Investigator. 
• Any topical administration (cutaneous, eye drops) of 
corticosteroids within the past 2 weeks.  
• Any individual currently receiving or having 
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(including systemic steroids, adrenocorticotrophic 
hormone or inhaled steroids) at a dose or duration 
potentially associated with hypothalamic-pituitary-
adrenal axis suppression within the past 12 months. 
10. Any contra-indication to rescue medication according to the 
applicable labelling and if found to be severely G6PD 
deficient at screening (i.e. activity of less than 10% as per 
WHO definition). 
11. Any history or presence of clinically relevant cardiovascular, 
pulmonary, gastrointestinal, hepatic/ gallbladder*/ bile duct, 
renal, 
metabolic, 
haematological, 
neurological, 
musculoskeletal, 
rheumatologic, 
systemic, 
ocular, 
gynaecologic (if female), infectious or autoimmune disease, 
or signs of acute illness. *including medical history of 
asymptomatic gallbladder stones. 
12. History of recurrent headache (eg, tension-type, cluster or 
migraine) with a frequency of ≥2 episodes per month on 
average and severe enough to require medical therapy. 
History of recurrent nausea and/or vomiting (for vomiting 
only: more than twice a month).  
13. Asthma (excluding childhood asthma, or mild asthma with 
preventative asthma medication required less than monthly 
and no event requiring treatment in the last 2 weeks prior to 
screening).  
14. Any personal history of surgical procedures or disease that 
may affect IMP absorption, distribution (i.e. GI surgery, 
malabsorption sydromes) and metabolism or immune 
response to malaria inoculation (splenectomy). 
15. Blood donation of any volume within one month before 
screening, or participation in any research study involving 
blood sampling (more than 450 mL/unit of blood).   
16. Any documented evidence of current or past cardiovascular 
disease including:  
• 
cardiac arrhythmias or  
• 
family history of congenital long QT syndrome, Brugada 
syndrome, or unexplained sudden cardiac death.  
• 
Symptomatic 
postural 
hypotension 
at 
screening 
irrespective of the decrease in blood pressure, or 
asymptomatic postural hypotension defined as a decrease 
in systolic blood pressure ≥20 mmHg after 3 min of 
changing from supine to standing position. 
17. Has evidence of increased cardiovascular risk (defined as 
>10%, 5-year risk for those greater than 35 years of age, as 
determined by the Australian Absolute Cardiovascular 
Disease Risk Calculator (http://www.cvdcheck.org.au). Risk 
factors include sex, age, systolic blood pressure (mm/Hg), 
smoking status, total and High-density lipoprotein (HDL) 
cholesterol (mmol/L) and reported diabetes status. Note: The 
site investigator will perform cardiovascular risk calculation 


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once all assessments have been performed, prior to 
eligibility. 
18. History 
or 
presence 
of 
diagnosed 
(by 
an 
allergist/immunologist) or treated (by a physician) food or 
known drug allergies, or any history of anaphylaxis or other 
severe allergic reactions including face, mouth, or throat 
swelling or any difficulty breathing. Individuals with known 
lactose or dairy intolerance are excluded. Volunteers with 
seasonal allergies/hay fever or allergy to animals or house 
dust mite that are untreated and asymptomatic at the time of 
dosing can be enrolled in the trial.  
19. History of convulsion (including drug or vaccine-induced 
episodes). A medical history of a single febrile convulsion 
during childhood is not an exclusion criterion.  
20. History of substance use disorder(s) within 5 years of 
screening and/or history of alcohol dependancy and/or 
any prior intravenous use of an illicit substance.  
21. Smoked > 1 pack of cigarettes per day for > 10 years, or who 
currently (within 14 days prior to screening) smokes > 5 
cigarettes per day.  
22. Any individual who, in the judgement of the Principal 
Investigator or delegate, is likely to be noncompliant during 
the study, or unable to cooperate because of a language 
problem or poor mental development.  
23. Any individual who cannot be contacted in case of 
emergency.  
24. Any individual who is the Investigator, or delegates, research 
assistant, pharmacist, study coordinator, project manager, or 
other staff thereof, directly involved in conducting the study.  
25. Any individual without a good peripheral venous access. 
26. Participation in any investigational product study within the 
12 weeks preceding inoculation with the malaria challenge 
agent or 5 times the half-life of the Investigational product, 
whichever is longer.  
27. Positive serology test for hepatitis B (positive HB sAG or 
anti-HBc Ab), hepatitis C (anti-HCV) or human immune 
deficiency virus (HIV) (positive for anti-HIV1 and anti-
HIV2 Ab).  
28. Positive urine drug test at Screening,  prior to inoculation 
with the malaria challenge agent or prior to IMP dosing.  Any 
drug from the list of drugs tested (such as amphetamine, 
barbiturates, benzodiazepines, cocaine, methamphetamine, 
methadone, Opiates, phencyclidine, Tetrahydrocannabinol; 
and their metabolites) unless there is an acceptable 
explanation to the Principal Investigator or delegate (eg, 
volunteer has stated in advance that they consumed a 
prescription of over the counter product which contained the 


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detected drug) and/or the volunteer has a negative urine drug 
screen on retest.  
29. Positive alcohol screen at Screening, prior to inoculation with 
the malaria challenge agent or prior to IMP dosing.  
30. Any consumption of citrus fruits (such as grapefruit, Seville 
oranges) or their juices within 7 days prior to IMP 
administration.    
31. History of serious psychiatric condition that may affect 
participation in the study or preclude compliance with the 
protocol, including but not limited to: past or present 
psychoses, disorders requiring lithium, a history of attempted 
or planned suicide, more than one previous episode of major 
depression, any previous single episode of major depression 
lasting for or requiring treatment for more than 6 months, or 
any episode of major depression during the 5 years preceding 
screening.  
Note: The Beck Depression Inventory will be used as an 
objective tool for the assessment of depression at screening. 
In addition to the conditions listed above, participants with a 
score of 20 or more on the Beck  Depression Inventory and/or 
a response of 1, 2 or 3 for item 9 of this inventory (related to 
suicidal ideation) will not be eligible for participation. 
Participants with a Beck score of 17 to 19 may be enrolled at 
the discretion of the Investigator if they do not have a history 
of the psychiatric conditions mentioned in this criterion and 
their mental state is not considered to pose additional risk to 
the health of the volunteer or to the execution of the study 
and interpretation of the data gathered.  
32. History of malignancy of any organ system (other than 
localized basal cell carcinoma of the skin or in situ cervical 
cancer considered treated and cured), treated or untreated, 
within 5 years of Screening, regardless of whether there is no 
evidence of local recurrence or metastases.  
33. Any vaccination within 28 days of screening.  
34. Any medical condition that in the opinion of the Principal 
Investigator or delegate would jeopardize the individual’s 
involvement in the study. 
 
Data Analysis 
Safety 
Safety analysis (AE, laboratory parameters, vital signs, ECGs) 
will be based on the review of individual values, and descriptive 
statistics. 
The safety analysis will focus on the TEAE period, defined as the 
time from the first IMP administration up to and including EOS.  
AEs will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA). Their severity will be graded 
according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE V5.0 27 Nov 2017). 


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The number (%) of volunteers experiencing TEAEs will be 
summarized by dose group. 
Safety analysis of ECGs will include in particular the number of 
volunteers with QTcF and/or QTcB prolongation of more than 30 
ms and 60 ms and/or QTc > 450 msec during the study.  
Pharmacodynamics 
Individual total parasitemia (measured by 18S qPCR) and female 
gametocytemia (measured by pfs25 RTPCR) profiles will be 
plotted. The individual asexual parasitemia profiles will be 
calculated as follows: if the gametocytemia level is lower than 
10% of the total parasitemia level, the asexual parasitemia level is 
assumed to be equal to the total parasitemia level; otherwise, the 
asexual parasitemia is considered unknown.  The asexual 
parasitemia profiles will be plotted individually and summarized 
by doses (median +/- 95% CI). 
The pharmacodynamic parameters (PCR, Pt1/2, lag phase) 
calculated as described in Marquart et al8 will be summarized 
using descriptive statistics (n, mean, geometric mean, standard 
deviation, median, Q1, Q3, minimum, and maximum) by dose 
group. The number and percentage of volunteers with absence of 
asexual parasitemia as well as the number and percentage of 
volunteers with recrudescence will be summarized by dose group. 
Pharmacokinetics 
MMV533 PK parameters will be calculated using non-
compartmental methods from plasma concentration-time 
data and will be summarized by dose group using descriptive 
statistics. 
• Plasma PK parameters: at least Cmax, tmax,  AUClast, 
AUC, t½, CL/F, Vss/F, Vz/F, plasma ratios of Cmax, 
AUClast and AUC 
Pharmacokinetics/pharmacodynamics 
• 
A population PKPD model will be derived from the plasma 
concentrations of MMV533 and asexual parasitemia levels  
in the challenge volunteers to quantify the relationship of 
plasma concentrations and the parasite killing/clearance. 
Several possible PD models may be tested and assessed by 
goodness-of-fit plots and BIC values to retain the best model. 
The estimated population PKPD parameters as well as their 
relative standard errors will be provided. Other key 
parameters will be derived from the PKPD model 
including minimum inhibitory concentration (MIC), the 
minimal parasiticidal concentration (MPC90), and the 
parasite reduction rate in 48 h (PRR48). 
Exploratory parameters  
If applicable, exploratory parameters will be summarized by 
treatment group using descriptive statistics and may be reported 
separately. Parasite drug resistance will be assessed by 


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calculating the IC50 of IMP and determining the percentage 
of surviving parasites using in vitro drug sensitivity testing. 
 
 


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1.2 
SCHEMA 
 


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1.3 
SCHEDULE OF ACTIVITIES 
Table 1: Schedule of Activities Overview 
 
Screening 
Pre-
inoculation 
Inocula 
tion 
Post-inoculation 
Phase 
Treatment and Posttreatment phase 
EOS/
ET 
Daya 
D-36 to D-
12 
D-11 to D-9 
D-8 
D-4 
D 
-3 
D 
-2 
D 
-1 
D
1 
D
2 
D
3 
D
4 
D
5 
D
6 
D
7 
D8 
± 2 
D
10 
D12 
D14
± 2 
D18  
D21
± 3 
D25
± 3 
D28 
± 3 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confinement 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Outpatient visit at clinical 
sitea 
X 
Xa 
Xa 
X 
X 
X 
 
 
 
 
 
 
Xa 
Xa 
X 
Xa 
Xa 
X 
Xa 
X 
X 
X 
Inclusion/exclusion 
criteria 
X 
X 
X pre 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical history 
X 
X 
X pre 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BDI-II 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV malaria challenge agent  
 
 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MMV533 (IMP) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rescue medication  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam - full 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical exam – symptom 
directed 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
G6PD status testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Red blood cells antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serology tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine drug screen, alcohol 
testc 
X 
 
X pre 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs supine and 
standing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs supine 
 
 
X pre & 
post 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre 
X 
 


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Screening 
Pre-
inoculation 
Inocula 
tion 
Post-inoculation 
Phase 
Treatment and Posttreatment phase 
EOS/
ET 
Daya 
D-36 to D-
12 
D-11 to D-9 
D-8 
D-4 
D 
-3 
D 
-2 
D 
-1 
D
1 
D
2 
D
3 
D
4 
D
5 
D
6 
D
7 
D8 
± 2 
D
10 
D12 
D14
± 2 
D18  
D21
± 3 
D25
± 3 
D28 
± 3 
12-lead ECG 
Xd 
 
Xd pre 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
X 
pre 
X 
X 
Body temperaturee 
X 
 
X pre 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre 
X 
X 
Hematology, 
biochemistry, urinalysis 
Xf 
Xf 
 
 
X 
 
Xf 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
X 
pre 
X 
X 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test/ FSHg 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serum Safety samplesh 
 
 
Xh pre 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xh 
Diary card 
 
 
X post 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
pre 
X 
X 
Malaria clinical score 
 
 
X pre & 
post 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
pre 
X 
X 
Adverse event collectioni 
Xi 
Xi 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MMV533 plasma samples 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Pharmacodynamics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitemia by qPCR 
 
 
X pre 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RT-PCR pfs25j 
 
 
 
 
 
 
 
Xj 
 
 
Exploratory 
 
Parasite drug resistance 
samplesk 
 
 
 
 
 
 
 
 
 
 
 
 
Xk 
 
 
OPTIONALl 
 
Research blood samplesl 
 
Xl 
 
 
 
 
 
Xl 
 
 
 
 
 
 
Xl 
 
 
 
 
 
 
Xl 
ABBREVIATIONS: BDI-II = Beck Depression Inventory; ECG = Electrocardiogram; EOS = End of study visit; ET = early termination visit; FSH = follicle stimulating 
hormone; IMP= Investigational Medicinal Product; NIMP= Non Investigational Medicinal Product; qPCR =quantitative polymerase chain reaction RT-PCR pfs25= 
gametocyte-specific mRNA transcript pfs25. 
NOTE: See Table 2 and Table 3 for more detailed timepoint and procedural information from Day -11 (pre-inoculation) onwards. This table 
provides an overview only.  
a. 
Volunteers will attend one visit between Days -11 to Day -9 to assess eligibility. One extra unscheduled visit is permitted if required for re-testing; results must be 
available prior to inoculation on Day -8. Eligibility must be confirmed prior to inoculation with the malaria challenge agent including from all assessments performed 


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pre-inoculation on Day -8. After inoculation with the malaria challenge agent on Day -8, clinical site staff will contact volunteers by telephone on Days -7 to Day -5 
to check on well-being. Volunteers are expected to be asymptomatic; if AEs are reported within this period, volunteers will attend the clinical unit for assessment of 
vital signs, body temperature, 12-lead ECG, symptom-directed physical examination, malaria clinical scroe and possible blood sampling for 18S qPCR. Outpatient 
visits on Days 6, 7, 10, 12 and 18 are suggested days only and optional at the discretion of the Principal Investigator or delegate. As a guide, volunteers should return 
twice daily (morning and evening) until parasite counts are <~500 parasites/mL, when visits may then be once daily. When parasite counts are <~200 parasites/mL, 
visits may be on alternate days, and once parasite counts are negative or low and stable, visits may be reduced to 3 times per week until rescue medication is 
administered. Rescue medication may be administered prior to Day 21±3 as described in Section 5.5.2.  
b. Volunteers will be inoculated with the malaria challenge agent and monitored for at least 60 minutes after inoculation with the malaria challenge agent before being 
permitted to leave the clinical unit. Volunteers will be issued with a volunteer card, diary and thermometer and educated on signs and symptoms of malaria. Post-
inoculation, the Investigator will consider COVID-19 symptoms when assessing any reported symptoms as per Note in Section 6.1.4.  
c. 
Drug test will be performed on urine sample. Alcohol test will be performed by breathalyser.  
d. 
Triplicate 12-lead ECGs required at screening, Day -8 prior to inoculation with malaria challenge agent and Day 1 pre-dose. All other ECGs are 12-lead single ECGs.  
e. 
Tympanic body temperature will be measured.   
f. 
The results of safety laboratory testing (hematology, biochemistry and urinalysis) from Day -11 to Day -9 (pre-inoculation) and Day -1 (pre-IMP dosing) must be 
available for review by the Investigator prior to inoculation with malaria challenge agent on Day -8 and IMP dosing on Day 1 respectively. At least 8 hours fasting 
required prior to sampling at Screening, visit(s) between Day -11 to -9, and Day -1.  
g. Serum β-human chorionic gonadotropin (hCG) pregnancy test for all female volunteers and FSH test for post-menopausal female volunteers at Screening. For WOCBP, 
urine β-hCG pregnancy test will be performed prior to inoculation with the malaria challenge agent on Day -8 and prior to IMP administration, and serum β-hCG 
pregnancy test conducted at EOS. If urine tests are positive, blood should be collected for serum β-hCG pregnancy test to confirm.  
h. Safety blood samples (IMP safety serum sample and Inoculum safety serum sample) will be collected on Day -8 prior to inoculation with the malaria challenge agent 
and at EOS. Sample volume will be 5 mL per sample. See Section 7.6.  
i. 
Untoward medical events recorded between screening and time of inoculation with malaria challenge agent will be recorded as medical history. Adverse events will 
be recorded continuously from time of inoculation with malaria challenge agent until EOS.  
j. 
The exact day(s) of sampling will be at the discretion of the Investigator if gametocytaemia is suspected or confirmed. 
k. One blood sample will be collected only if recrudescence occurs to investigate parasite drug resistance. This sample will be collected just prior to administration of 
rescue medication, and timing of  sample collection will be flexible at the discretion of the Investigator in the event that rescue medication is administered early due 
to recrudescence. Recrudescence is defined as ≥5000 blood stage parasites per mL after initial parasite clearance accompanied by either a two-fold parasitaemia 
increase within 48 hours, or reoccurrence of malaria symptoms with a malaria clinical score of  ≥6.  
l. 
OPTIONAL: These research samples may only be collected at the timepoints indicated if the volunteer has consented to the separate QIMR study under the local 
Sponsorship of QIMR Berghofer Institute – see Section 7.6. Sample on Day 1 is pre-dose. 
 
 
 
 


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Table 2: Day -11 to Day 1 Detailed Schedule of Activities 
 Day -11 to Day 1 
D-
11 
to 
D-9 
D 
-8a 
D-4 
D-3 
 
D-2 
 
D-1 
 
 
D1 
Time hour (H) 
minutesb 
 
 
 
am 
pm 
am 
pm 
am 
pm 
Pre-
dose 
0H 
0H 
30 
1H 
1H 
30 
2H 
3H 
4H 
6H 
8H 
10H 
12H 
16H 
20H 
Confinement 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Outpatient visit at 
clinical site 
X 
Xc 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusio
n criteria 
X 
Xc 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical 
history 
X 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
Xc 
X 
X 
X 
X 
X 
X 
Inclusion 
 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV malaria 
inoculum (NIMP) 
 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MMV533 (IMP) 
 
 
 
 
 
 
 
 
 
 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
Rescue 
medication 
(NIMP)f 
 
 
 
 
 
 
 
 
 
 
Xf 
 
 
 
 
 
 
 
 
 
 
 
 
Safetyg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
 
Xc,
h 
Xh 
Xh 
Xh 
Xh 
Xh 
Xh 
Xh 
Xh 
 
Xh 
Body weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen, 
alcohol testi 
 
Xc 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
(supine)j 
 
Xj 
X 
X 
Xk 
X 
X 
X 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
 
12-lead ECGl 
 
Xc,l 
 
 
 
 
 
X 
 
Xl 
 
 
 
 
 
 
X 
X 
X 
 
X 
 
 
Body temperature 
 
Xc 
X 
X 
Xk 
X 
X 
X 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
 


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 Day -11 to Day 1 
D-
11 
to 
D-9 
D 
-8a 
D-4 
D-3 
 
D-2 
 
D-1 
 
 
D1 
Time hour (H) 
minutesb 
 
 
 
am 
pm 
am 
pm 
am 
pm 
Pre-
dose 
0H 
0H 
30 
1H 
1H 
30 
2H 
3H 
4H 
6H 
8H 
10H 
12H 
16H 
20H 
Haematology, 
biochemistry, 
urinalysis 
Xm 
 
 
Xm 
LFT 
 
 
 
Xn 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine β-hCG 
(WOCBP only) 
Xo 
 
 
 
 
 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum safety 
samples 
 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary card 
 
Xp 
X 
X 
Xk 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malaria clinical 
score 
 
Xj 
X 
X 
Xk 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
Adverse event 
collectionq 
Xq 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic
s 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MMV533 + 
metabolites 
plasma  samples 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Pharmacodynam
ics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitaemia by 
qPCR 
 
Xc 
X 
Xr 
Xr 
Xr 
Xk,
r 
Xr 
Xk,
r 
X 
 
 
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
OPTIONALs 
 
Research blood 
sampless 
Xs 
 
 
 
 
 
 
 
Xs 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABBREVIATIONS: ECG = electrocardiogram; IMP = investigational medicinal product; NIMP = noninvestigational medicinal product; qPCR =quantitative polymerase 
chain reaction; qRT-PCR pfs25= Reverse-transcription polymerase chain reaction for the gametocyte-specific mRNA transcript pfs25; WOCBP = woman of child bearing 
potential.  
a. 
After inoculation with the malaria challenge agent on Day -8, clinical site staff will contact volunteers by telephone daily on Days -7 to Day -5 to check on well-being. 
There are no outpatient visits to the clinical site scheduled for Days -7 to -5 as volunteers are expected to be asymptomatic. If AEs are reported during this period, 
volunteers will attend the clinical unit  for assessment of vital signs, body temperature, 12-lead ECG, symptom-directed physical examination, malaria clinical score and 


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possible blood sampling for 18S qPCR at discretion of the Investigator. Post-inoculation, the Investigator will consider COVID-19 symptoms when assessing any reported 
symptoms as per Note in Section 6.1.4. 
b. Time (hour/minute) is expressed in reference to the single administration of IMP at t = 0 (T0H).  
c. 
Activities/procedures to be conducted prior to inoculation with the malaria challenge agent.  
d. Eligible volunteers will be injected with malaria challenge agent containing approximately 2800 viable human erythrocytes infected with P. falciparum 3D7 paraiste in 
2 mL saline and then monitored for at least 60 minutes before being permitted to leave the clinical unit.All volunteers attending on the same day will be inoculated 
within a 60 minute period and within 4 hours of preparation of the malaria challenge agent.  
e. 
A fasting single oral dose of MMV533 (IMP) will be administered with 240 mL water. Dose will depend on cohort. Post-IMP: volunteers to remain seated for 10 
minutes, stay semi-recumbent for next 2 hours (except if safety assessments require lying position), no food for 4 hours and no liquids for 1 hour. Prior to IMP dosing 
on Day 1, the Principal Investigator or delegate should ensure that no contraindication to administration of IMP are present as described in Section 4.3.8.1 (in which 
case rescue medication should be administered instead of IMP).  
f. 
Rescue medication may be given earlier than Day 21±3 or instead of IMP on Day 1 in the event of: withdrawal of inoculated volunteer and/or as outlined in 
Section 4.3.8.1 and Section 5.5.2.  
g. Refer to Safety Section 7 for detailed safety investigations.  
h. Symptom-directed physical examination only. Body systems will be reviewed only if clinically indicated and at the discretion of the Principal Investigator or delegate.  
i. 
Drug test will be performed on urine sample. Alcohol test will be performed by breathalyzer. 
j. 
Vital signs (supine for 5 minutes; heart rate beats per minute; blood pressure diastolic and systolic mmHg). Vital signs and malaria clinical score will be performed 
before and approximately 60 minutes after inoculation at Day -8.  
k. At discretion of the Principal Investigator or delegate. 
l. 
Automatic reading. Triplicate standard 12-lead ECGs required prior to inoculation and on Day 1 pre-IMP dose. Single standard 12-lead ECGs at all other timepoints. 
m. Participants will have fasted for at least 8 hours prior to sampling at visit/s between Day -11 to Day -9. Results of clinical safety laboratory tests conducted at the visit/s 
during Day -11 to -9 must be available for review prior to inoculation on Day -8. Liver funtction tests (LFTs) are the only safety laboratory tests required on Day -3.  
n. Participants will have fasted for at least 8 hours prior to sampling on Day -1. The results of clinical safety laboratory tests conducted on Day -1 must be available and 
reviewed by the Principal Investigator or delegate prior to administration of IMP on Day 1.  
o. If urine tests are positive, blood should be collected for serum β-hCG pregnancy test to confirm.   
p. After inoculation with the malaria challenge agent and prior to leaving the clinical unit, each volunteer will be issued a volunteer card, diary and thermometer to record 
temperature in the event of fever, and to record adverse events and concomitant medications. Volunteers will be educated on the signs and symptoms of malaria and 
how to fill in the diary. Volunteers should bring diaries to each subsequent visit to the clinical unit.  
q. Untoward medical events prior to time of inoculation with malaria challenge agent will be recorded as medical history. Adverse events will be recorded from time of 
inoculation with malaria challenge agent until EOS.  
r. 
Samples for 18s qPCR will be collected twice daily or at the discretion of the Principal Investigator or delegate.  
s. 
OPTIONAL: These research samples may only be collected at the timepoints indicated if the volunteer has consented to the separate QIMR study under the local 
Sponsorship of QIMR Berghofer Institute – see Section 7.6. 
NOTE:  
• 
When several assessments take place at the same time, the following order should be respected: ECG, vital signs, blood sampling, drug administration, meal.  


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• 
To respect exact timing of pharmacokinetic samples, the other measures will be done ahead of the scheduled time.  
• 
Diary cards and a thermometer will be issued to volunteers for completion at home (including temperature monitoring and recording AEs and concomitant medications). 
Volunteers will be educated on the signs and symptoms of malaria and how to complete the diary prior to leaving the clinical unit.   
• 
Time windows for PK and PD sampling are described in Table 5.  
• 
Time windows for assessments conducted from Day 1 are described per assessment section (if applicable) in Section 7.   
 
 


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Table 3: Day 2 to Day 28 Detailed Schedule of Activities 
Study Day 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
±2 
D10 
D12 
D14 
±2 
D18 
D21 
±3 
D25 
±3 
EOS 
D28 
±3 
 
Time (hours post-
IMP )a 
24
H 
30
H 
36
H 
48
H 
60
H 
72
H 
84
H 
96H 
108
H 
120
H 
132
H 
144 
H 
168
H 
192 
H 
264 
H 
312H 
408
H 
Pre 
480H 
576H 
648H 
Confinement 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Outpatient visit at 
clinical site 
 
 
 
 
 
 
 
 
 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
X 
X 
X 
Concomitant 
medications 
X 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
X 
X 
X 
Study treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rescue medication  
(Non-IMP)c 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xc 
 
 
Safetyd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
Xe 
Xe 
Xe 
Xe 
Xf 
Xe,b 
Xb 
Xe,
b 
Xe 
Xeb 
Xe,b 
Xe 
Xe,b 
Xe 
Xe 
Xe 
Xe 
Body weight 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine drug screen, 
alcohol testg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
 
X 
Xh 
12-lead ECGi 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
X 
Body temperature 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
 
X 
X 
Serology 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Red blood cells 
antibodies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology, 
biochemistry,  
X 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
X 
Urinalysis 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
X 
 
 
X 
Serum β-hCG 
(WOCBP only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 


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Study Day 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
±2 
D10 
D12 
D14 
±2 
D18 
D21 
±3 
D25 
±3 
EOS 
D28 
±3 
 
Time (hours post-
IMP )a 
24
H 
30
H 
36
H 
48
H 
60
H 
72
H 
84
H 
96H 
108
H 
120
H 
132
H 
144 
H 
168
H 
192 
H 
264 
H 
312H 
408
H 
Pre 
480H 
576H 
648H 
Serum safety 
samplesj 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xj 
Diary card review 
 
 
 
 
 
 
 
 
 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
 
X 
X 
Malaria clinical 
score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
 
X 
X 
Adverse event 
collection 
X 
Xb 
Xb 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
X 
X 
X 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MMV533 plasma  
PK samples 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
 
X 
Pharmacodynamic
s 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitaemia by  
18S qPCR 
X 
X 
X 
X 
X 
X 
X 
Xk 
Xk 
Xbk 
Xbk 
Xb 
X 
Xb 
Xb 
X 
Xb 
X 
 
X 
X 
RT-PCR pfs25 
 
 
 
 
 
 
 
Xl 
 
Exploratory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasite drug 
resistance samplesm 
 
 
 
 
 
 
 
 
 
Xm 
Xm 
 
 
 
OPTIONALn 
 
Research blood 
samplesn 
 
 
 
 
 
 
 
 
 
 
 
 
Xn 
 
 
 
 
 
 
 
Xn 
ABBREVIATIONS: ECG = electrocardiogram; IMP = investigational medicinal product; NIMP = noninvestigational medicinal product; qPCR =quantitative polymerase 
chain reaction; qRT-PCR pfs25= Reverse-transcription polymerase chain reaction for the gametocyte-specific mRNA transcript pfs25; WOCBP = woman of child 
bearing potential. 
a. 
Time (hours) is expressed in reference to the single administration of IMP at t = 0 hours (H).  
b. Procedures/activities will be conducted at the discretion of the Principal Investigator or delegate Visits to the clinical unit on Days 6, 7, 10, 12 and 18 are suggested 
days only and optional at the discretion of the Principal Investigator or delegate. Adverse events will continue to be recorded at each outpatient visit and if reported 
or observed at other times. As a guide, volunteers should return twice daily (morning and evening) until parasite counts are <~500 parasites/mL, when visits may 
then be once daily. When parasite counts are <~200 parasites/mL, visits may be on alternate days, and once parasite counts are negative or low and stable, visits may 
be reduced to 3 times per week until rescue medication is administered.  


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c. 
Volunteers will be administered mandatory malaria rescue medication (Riamet®) on Day 21±3, or earlier if there is failure of clearance or recrudescence of 
parasitemia or at the discretion of the Principal Investigator or delegate or due to volunteer withdrawal or safety issue (see Section 4.3.8.1 and Section 5.5.2). In case 
of early rescue treatment administration, associated safety assessments must be continued as per the Schedule of Activities for rescue medication. Malaria clinical 
score and parasitemia by qPCR should be continued for up to 72h as per the Schedule of Activities and must be performed as a minimum 72h post rescue treatment 
administration or at the discretion of the Principal Investigator or delegate. Malarone® may be given if allergy or contraindication to Riamet® occurs or is 
suspected. The first dose of oral antimalarial rescue treatment will be administered at the clinical unit, with subsequent doses taken by the volunteer at home and 
recorded in the diary. Clinical unit staff must contact the volunteer on a daily basis during the dosing period to confirm compliance. Intravenous Artesunate may be 
given if volunteer unable to tolerate oral antimalarial rescue treatment. Primacin™ will be administered at the discretion of the Investigator in addition to Riamet® if 
gametocytaemia is indicated. Post-inoculation, the Investigator will consider COVID-19 symptoms when assessing any reported symptoms as per Note in Section 
6.1.4. 
d. Refer to Safety Section 7 for detailed safety investigations,  
e. 
Full physical examination at EOS only. Symptom-directed physical examination at all other designated timepoints - body systems to be reviewed only if clinically 
indicated and at the discretion of the Principal Investigator or delegate.  
f. 
Prior to volunteer discharge from confinement, clinical unit nursing staff must confirm with the Principal Investigator or delegate if any volunteer requires a 
symptom-driven examination before discharge. 
g. 
Unscheduled drug and alcohol screening may be performed if required for volunteer safety or to assess continued eligibility at the discretion of the Principal Investigator 
or delegate.  Drug test will be performed on urine sample. Alcohol test will be performed by breathalyzer.  
h. Vital signs (supine for 5 minutes; heart rate beats per minute; blood pressure diastolic and systolic mmHg;).Supine and standing vital signs (measured after supine 5 
minutes then after standing for 3 minutes) will be performed at EOS.  
i. 
Automatic reading. Single standard 12-lead ECGs.  
j. 
Safety blood samples (IMP safety serum sample and Inoculum safety serum sample) will be collected on Day -8 prior to inoculation with the malaria challenge agent 
and at EOS. Sample volume will be 5 mL per sample. See Section 7.6. 
k. Samples for 18s qPCR will be collected at the discretion of the Principal Investigator – see footnote (b). Two negative 18s qPCR results are required prior to EOS.   
l. 
Samples for qRT-PCR will be collected from Day 5 onwards at the discretion of the Principal Investigator and if 18 qPCR data suggest presence of gametocytes in 
volunteers' blood. 
m. Blood samples will be collected prior to first dose of rescue medication only if recrudescence occurs to investigate parasite drug resistance. Recrudescence is defined 
as ≥ 5000 blood stage parasites per mL after initial parasite clearance accompanied by either a two-fold parasitaemia increase within 48 hours, or reoccurrence of 
malaria symptoms with a malaria clinical score ≥6.  
n. OPTIONAL: These research samples may only be collected at the timepoints indicated if the volunteer has consented to the separate QIMR study under the local 
Sponsorship of QIMR Berghofer Institute – see Section 7.6.  
NOTE:  
- 
When several items take place at the same time, the following order should be respected: ECG, vital signs, blood sampling, drug administration, meal.  
To respect exact timing of pharmacokinetic samples, the other measures will be done ahead of the scheduled time.  


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- 
The diary card issued to the volunteer on D-8   will be checked at each outpatient visit. Volunteers will enter into the diary cards data relating to their daily physical 
activity, daily alcohol consumption, any symptoms of malaria and if applicable, their oral temperature. Volunteers will bring their completed diary cards with them 
to the trial site for all ambulant, Follow-up, and EOS visits.  
- 
Days 6, 7, 10, 12 and 18 are optional at the discretion of the Principal Investigator or delegate – see footnote (b). 
 


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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ...................................................................................... 2 
1.1 
PROTOCOL SYNOPSIS .......................................................................................... 2 
1.2 
SCHEMA ............................................................................................................ 14 
1.3 
SCHEDULE OF ACTIVITIES ................................................................................. 15 
2 
INTRODUCTION AND RATIONALE .............................................................. 35 
2.1 
DISEASE BACKGROUND .................................................................................... 35 
2.2 
INVESTIGATIONAL MEDICINAL PRODUCT - MMV533 ...................................... 35 
2.2.1 Clinical Studies ............................................................................................ 36 
2.2.2 Non-Clinical Studies .................................................................................... 36 
2.2.3 Safety and Risk/Benefit Assessment ............................................................. 37 
2.3 
RATIONALE ....................................................................................................... 38 
2.3.1 Rationale for the Study ................................................................................ 38 
2.3.2 Rationale for the Dose ................................................................................. 38 
3 
STUDY OBJECTIVES AND ENDPOINTS ....................................................... 40 
4 
INVESTIGATIONAL PLAN ............................................................................... 42 
4.1 
DESCRIPTION OF OVERALL STUDY DESIGN AND PLAN ..................................... 42 
4.1.1 Induced Blood Stage Malaria (IBSM) ......................................................... 42 
4.2 
DISCUSSION OF STUDY DESIGN INCLUDING CHOICE OF CONTROL GROUPS ...... 43 
4.3 
SELECTION OF STUDY POPULATION .................................................................. 43 
4.3.1 Inclusion Criteria ......................................................................................... 43 
4.3.2 Exclusion Criteria ........................................................................................ 45 
4.3.3 Lifestyle Considerations .............................................................................. 48 
4.3.4 Screen Failures ............................................................................................ 49 
4.3.5 Withdrawal of Volunteers ............................................................................ 50 
4.3.6 Lost to Follow-Up ........................................................................................ 51 
4.3.7 Study Discontinuation .................................................................................. 51 
4.3.8 Trial Intervention/Treatment Discontinuation – Stopping Rules ................ 51 
4.4 
RISK/BENEFIT ASSESSMENT OF STUDY TREATMENTS AND INTERVENTIONS 
OTHER THAN IMP ......................................................................................................... 53 
4.4.1 Malaria Challenge Agents and the IBSM .................................................... 53 
4.4.2 Malarial Rescue Medication/s ..................................................................... 55 
5 
TRIAL INTERVENTIONS/TREATMENTS ..................................................... 55 
5.1 
INVESTIGATIONAL MEDICINAL PRODUCT (IMP) ............................................... 55 
5.1.1 MMV533 ...................................................................................................... 55 
5.2 
IBSM MODEL MALARIA CHALLENGE AGENT ................................................... 55 
5.3 
MALARIA RESCUE MEDICATIONS ..................................................................... 56 
5.3.1 Riamet® (Artemether-lumefantrine) ............................................................. 56 
5.3.2 If Gametocytaemia is suspected/confirmed ................................................. 56 
5.3.3 If an Allergy or Contraindication to Riamet® Develops ............................. 57 
5.3.4 If Volunteer Vomits or Cannot Tolerate Oral Malarial Treatment ............. 57 
5.4 
SELECTION OF DOSE IN THE STUDY .................................................................. 57 
5.4.1 MMV533 ...................................................................................................... 57 
5.4.2 Other Study Treatments/Interventions ......................................................... 58 
5.5 
SELECTION AND TIMING OF DOSE FOR EACH VOLUNTEER ................................ 58 


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5.5.1 MMV533 ...................................................................................................... 58 
5.5.2 Other Study Treatments/Interventions ......................................................... 59 
5.6 
DOSE INTERRUPTIONS AND REDUCTIONS .......................................................... 59 
5.7 
SUPPLY, PACKAGING AND LABELLING OF STUDY TREATMENTS ....................... 59 
5.7.1 MMV533 ...................................................................................................... 60 
5.7.2 Malaria Challenge Agent............................................................................. 60 
5.7.3 Malarial rescue medications ....................................................................... 60 
5.8 
STORAGE OF STUDY TREATMENTS ................................................................... 60 
5.9 
ACCOUNTABILITY, RECONCILIATION AND RETURN OF THE STUDY TREATMENTS
 
60 
5.10 
PROHIBITED CONCOMITANT THERAPY ............................................................. 61 
5.11 
TREATMENT COMPLIANCE ................................................................................ 61 
5.12 
MEASURES TO MINIMIZE BIAS .......................................................................... 62 
5.12.1 Randomisation Procedures .......................................................................... 62 
6 
STUDY ASSESSMENTS AND PROCEDURES ................................................ 62 
6.1 
STUDY CONDUCT SCHEDULE ............................................................................ 62 
6.1.1 Screening ..................................................................................................... 62 
6.1.2 Inclusion/Eligibility Visit ............................................................................. 62 
6.1.3 Day -8 Inoculation with Malaria Challenge Agent ..................................... 63 
6.1.4 Days -7 to -5 Malaria monitoring by phone ................................................ 64 
6.1.5 Day -4 until Day -1 Outpatient Visits .......................................................... 64 
6.1.6 Day -1 to Day 5 Confinement for IMP administration ................................ 65 
6.1.7 Post-confinement Outpatient Monitoring Visits .......................................... 67 
6.1.8 Mandatory Malaria Rescue Medication ...................................................... 67 
6.1.9 Unscheduled Monitoring Outpatient Visits ................................................. 68 
6.1.10 Day 28±3 EOS ............................................................................................. 68 
6.2 
PHARMACODYNAMIC PRIMARY ASSESSMENT ................................................... 69 
6.2.1 Malaria 18S qPCR ....................................................................................... 69 
6.3 
OTHER PHARMACODYNAMIC PARAMETERS ...................................................... 70 
6.3.1 pfs25 qRT-PCR ............................................................................................ 70 
6.3.2 Parasite Drug Resistance ............................................................................ 70 
6.4 
PHARMACOKINETICS ......................................................................................... 70 
7 
SAFETY ASSESSMENTS .................................................................................... 71 
7.1 
PHYSICAL EXAMINATION .................................................................................. 71 
7.2 
VITAL SIGNS, TEMPERATURE AND BODY MEASUREMENTS .............................. 72 
7.2.1 Body Measurements and Temperature ........................................................ 72 
7.2.2 Vital signs .................................................................................................... 72 
7.3 
12-LEAD ELECTROCARDIOGRAM (ECG) .......................................................... 73 
7.4 
MALARIA CLINICAL SCORE .............................................................................. 73 
7.5 
CLINICAL LABORATORY TESTS ........................................................................ 74 
7.5.1 Safety Blood Tests ........................................................................................ 74 
7.5.2 Coagulation ................................................................................................. 75 
7.5.3 Serology ....................................................................................................... 75 
7.5.4 Pregnancy and Follicle Stimulating Hormone (FSH) Testing .................... 75 
7.5.5 Red Blood Cell alloantibodies ..................................................................... 75 
7.5.6 Urinalysis ..................................................................................................... 75 
7.6 
RETENTION SAMPLES ........................................................................................ 76 
7.7 
ALCOHOL AND DRUG SCREENING ..................................................................... 77 


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7.8 
BECK DEPRESSION INVENTORY ........................................................................ 77 
7.9 
ADVERSE EVENTS (AES) .................................................................................. 77 
7.9.1 Definitions .................................................................................................... 77 
7.9.2 Causal Relationship to Investigational Medicinal Product and Other Study 
Treatments ............................................................................................................... 78 
7.9.3 Severity Grading of Adverse Events ............................................................ 79 
7.9.4 Documentation of Adverse Events ............................................................... 79 
7.9.5 Adverse Events of Special Interest (AESI) ................................................... 80 
7.9.6 Treatment of Overdose................................................................................. 81 
7.10 
SERIOUS ADVERSE EVENTS (SAES).................................................................. 81 
7.10.1 Definitions of Serious Adverse Events (SAEs) ............................................. 81 
7.10.2 Pregnancy .................................................................................................... 82 
7.10.3 Reporting for Serious Adverse Events (24 hours) ....................................... 82 
7.11 
SAFETY REVIEW COMMITTEE (SRC) ................................................................ 83 
8 
STATISTICAL ANALYSES ................................................................................ 83 
8.1 
GENERAL APPROACH ........................................................................................ 83 
8.2 
SAMPLE SIZE AND JUSTIFICATION ..................................................................... 84 
8.3 
ANALYSIS SETS AND SUB-SETS ......................................................................... 84 
8.3.1 Analysis Sets ................................................................................................ 84 
8.4 
VOLUNTEER DISPOSITION ................................................................................. 84 
8.5 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS ......................................... 85 
8.5.1 Demographics .............................................................................................. 85 
8.5.2 Medical History ........................................................................................... 85 
8.5.3 Prior Medications ........................................................................................ 85 
8.5.4 Eligibility ..................................................................................................... 85 
8.6 
PROTOCOL DEVIATIONS .................................................................................... 85 
8.7 
TREATMENT EXPOSURE .................................................................................... 85 
8.8 
SAFETY (PRIMARY ENDPOINT).......................................................................... 85 
8.8.1 Safety Endpoints .......................................................................................... 85 
8.8.2 Adverse Events ............................................................................................. 85 
8.8.3 Concomitant Medications ............................................................................ 86 
8.8.4 Laboratory Findings .................................................................................... 86 
8.8.5 Physical Examination .................................................................................. 87 
8.8.6 Body Measurements and Body Temperature ............................................... 87 
8.8.7 Vital Signs .................................................................................................... 87 
8.8.8 12-lead ECG ................................................................................................ 87 
8.9 
PHARMACOKINETIC ENDPOINTS ....................................................................... 87 
8.9.1 Pharmacokinetic Parameters ...................................................................... 87 
8.9.2 Pharmacokinetics/pharmacodynamics ........................................................ 87 
8.10 
PHARMACODYNAMIC ENDPOINTS ..................................................................... 88 
8.11 
EXPLORATORY PARAMETERS ........................................................................... 88 
8.12 
INTERIM ANALYSIS ........................................................................................... 88 
9 
STUDY ADMINISTRATION .............................................................................. 88 
9.1 
ETHICAL CONSIDERATIONS ............................................................................... 88 
9.1.1 Ethical Principles ........................................................................................ 88 
9.1.2 Informed Consent ......................................................................................... 88 
9.1.3 Investigator and Human Research Ethics Committee (HREC) 
Responsibilities ........................................................................................................ 89 


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9.2 
PROTOCOL ADHERENCE .................................................................................... 89 
9.3 
PROTOCOL AMENDMENTS ................................................................................ 89 
9.4 
DATA HANDLING AND RECORD KEEPING ......................................................... 90 
9.5 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................... 90 
9.6 
PUBLICATION POLICY ....................................................................................... 90 
10 REFERENCES....................................................................................................... 91 
11 APPENDICES ........................................................................................................ 93 
APPENDIX 1: SPONSOR APPROVED CLINICALLY ACCEPTABLE INCLUSION LABORATORY 
RANGES ........................................................................................................................ 93 
APPENDIX 2: MALARIA CLINICAL SCORE ..................................................................... 95 
 
 


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List of Tables  
Table 1: Schedule of Activities Overview ....................................................................... 15 
Table 2: Day -11 to Day 1 Detailed Schedule of Activities ............................................ 18 
Table 3: Day 2 to Day 28 Detailed Schedule of Activities .............................................. 22 
Table 4: Observed  (5 and 10 mg MMV533) and Predicted (20-400 mg MMV533) mean 
group AUC inf for each MMV533 dose level evaluated in the FIH Study ..................... 36 
Table 5: Permitted PK and PD Blood Sampling Time Windows .................................... 71 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ACT 
Artemisinin-based combination therapy 
ADME 
Absorption, distribution, metabolism, excretion 
AE 
Adverse event 
Ae0-t 
Cumulated amount of drug excreted in urine from time 0 to time t 
ALT 
Alanine aminotransferase 
AST 
Aspartate transaminase 
AUC 
Area under the curve 
BDI 
Beck Depression Inventory 
BMI 
Body mass index 
CLR0-t 
Renal clearance of drug estimated from time 0 to time t 
Cmax 
Maximum plasma concentration observed 
DBP 
Diastolic blood pressure 
DME/T 
Drug metabolism enzymes and drug transporters 
ECG 
Electrocardiogram  
EOS 
End of study visit 
FDA 
Food and Drug Administration (US) 
fe0-t 
Fraction of dose of drug excreted in urine from time 0 to time t 
FSH 
Follicle stimulating hormone 
HDL 
High density lipoprotein 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
HREC 
Human Research Ethics Committee 
IBSM 
Induced blood stage malaria 
IC50 
Concentration for 50% inhibition 
IMP 
Investigational medicinal product 
LFT 
Liver function tests 
LOQ 
Limit of quantification 
MCB 
Master cell bank 
MMV 
Medicines for Malaria Venture 
MPC 
Minimum drug concentration above which parasite clearance is 
maximal 
OTC 
Over the counter  
PBPK 
Physiologically based pharmacokinetics 
PD 
Pharmacodynamics  
PK 
Pharmacokinetics  
PKPD 
Pharmacokinetic-pharmacodynamic  
PRR48 
Parasite reduction ratio over 48 hours 


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Pt1/2 
Parasite clearance half-life 
SAD 
Single ascending dose 
SBP 
Systolic blood pressure 
SCID 
Severe combined immunodeficiency (mouse model) 
SRC 
Safety Review Committee 
SSR 
Southern Star Research Pty Ltd 
t1/2z 
Terminal half-life  
TEAE 
Treatment emergent adverse event 
tlag 
Lag time  
tmax 
Time to reach maximum plasma concentration (Cmax) 
VIS 
Volunteer infection study 
Vss/F  
Apparent volume of distribution at the steady state after single 
dose 
Vz/F 
Apparent volume of distribution after single dose 
WHO 
World Health Organisation 
 
 


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PROTOCOL APPROVAL/ SIGNATURES 
I herewith approve the following protocol entitled “A Phase 1b study to assess the 
safety, tolerability and antimalarial activity of MMV533 against Plasmodium 
falciparum blood stage infection in healthy volunteers.”, Version 1.0. dated 01 March 
2021. Effective date 02 March 2021.  
 
SPONSOR SIGNATURE 
 
 Signature: 
_______________________________________________ 
Name: 
Dr Stephan Chalon MD PhD 
Role: 
Medical Director, Medicines for Malaria Venture 
Date: 
____/____/2021 
 
 Signature: 
_______________________________________________ 
Name: 
Dr Amina Haouala PhD 
Role: 
Clinical Science Lead, Medicines for Malaria Venture 
Date: 
____/____/2021 
 
 
01  03
01
03




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2 INTRODUCTION AND RATIONALE 
MMV533 is in development as a potential single dose cure, fast acting and long-lasting 
treatment for malaria. At the writing of this study protocol, the very First In Human study 
with MMV533 has been initiated in Australia in August 2020.  
2.1 
DISEASE BACKGROUND 
Malaria continues to be a challenge globally. In 2018, some 228 million cases of malaria 
occurred worldwide, resulting in an estimated 405,000 deaths.1 Although the incidence 
rate of malaria globally is declining, the rate of decline has slowed dramatically, 
remaining at similar levels to that reported in 2014. In 2018, nineteen countries in sub-
Saharan Africa and India accounted for almost 85% of global malaria cases, and 94% of 
all malaria deaths were from the African region.  
Malaria is a cyclical parasitic infection of humans and female Anopheles mosquitoes.2 As 
a brief summary, after a female Anopheles mosquito feeds on the blood of a human 
infected with the malarial parasite it is asymptomatically infected with the parasite. The 
parasites grow and multiply in the gut of the mosquito before migrating to its salivary 
glands, and the infected mosquito then injects some of the infected saliva into the next 
human it feeds on. In the human, the parasites first migrate to the liver before infecting 
red blood cells, where the cycle continues with successive generations of asexual parasites 
invading and destroying red blood cells. These blood stage parasites cause the symptoms 
of malaria. After a period of time, some of the blood stage parasites differentiate into male 
and female forms (gametocytes) which continue the cycle of infection when ingested by 
a female Anopheles mosquito feeding on the infected human. Worldwide, Plasmodium 
falciparum is the predominant malaria parasite, causing the vast majority of cases in 
Africa and many cases in South-East Asia, Eastern Mediterranean region and the Western 
Pacific Region.1  
The World Health Organisation (WHO) promotes several strategies to help combat 
malaria, including preventing mosquito bites with use of insecticide-treated mosquito nets 
while sleeping and insecticide spraying of indoor walls, use of preventative therapies 
especially for vulnerable groups such as children and pregnant women, and improve 
improving institutional structures for accessing care to diagnose and treat malaria.1 For 
treatment of malaria, artemisinin-based combination therapy (ACT) has been widely 
implemented, with an estimated 3 billion courses of ACT procured globally between 2010 
and 2018. However, parasite resistance to artemisinin and other therapies are becoming 
more common especially in Thailand and other South-East Asian countries, while 
mosquito resistance to insecticide is also widespread.  
Therefore, there remains an urgent need to continue the clinical development of novel, 
effective and well-tolerated anti-malarial drugs, of which MMV533 is a promising 
candidate.   
2.2 
INVESTIGATIONAL MEDICINAL PRODUCT - MMV533 
MMV533 is a first in class, fast acting, orally bioavailable blood stage inhibitor of 
Plasmodium falciparum with a long half-life. Its mechanism of action is unknown. 
MMV533 is being developed for the curative treatment of uncomplicated malaria caused 
by P. falciparum in adults and children, and has been evaluated in a range of preclinical 
pharmacological models of malaria.  


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2.2.1 Clinical Studies 
MMV533 is being tested in humans in the ongoing First-in-Human (FIH) study 
MMV_MMV533_19_01 investigating safety, tolerability and pharmacokinetics of 
MMV533 in healthy adult male and female volunteers. 
At the time of writing of this document, the first two cohorts (5 and 10 mg) of the 
MMV533 FIH study had completed (n=16 volunteers; 4 placebo and 12 IMP). No serious 
or severe AEs were observed, and Cohort 3 (20 mg) commenced in January 2021. 
Preliminary 
human 
PK 
analysis 
obtained 
from 
the 
ongoing 
FIH 
(study 
MMV_MMV533_19_01), show a long half-life of approximately 120 hours and 
acceptable intersubject variability. Observed peak concentrations and AUC0-inf at 5 and 
10 mg MMV533 (Table 4) showed higher than anticipated exposure. This therefore 
suggests that the highest dose to be evaluated in the FIH will not exceed 200 mg MMV533 
in order not to exceed the AUC cap (125 µg.h/ml) identified for this project. 
Table 4: Observed  (5 and 10 mg MMV533) and Predicted (20-400 mg MMV533) 
mean group AUC inf for each MMV533 dose level evaluated in the FIH Study 
Dose MMV533 
 (mg) 
AUCinf (µg/mL*hr) 
Safety Margin - Dog NOAEL 
(125 µg/mL*hr) 
5 
3.0 
41.2 
10 
6.1 
20.6 
20 
12.1 
10.3 
50 
30.3 
4.1 
100 
60.7 
2.1 
200 
121.3 
1.0 
400 
242.7 
0.5 
ABBREVIATIONS: AUC = area under the curve; FIH = first-in-human; NOAEL = no observed adverse 
effect level; PK = pharmacokinetics.  
2.2.2 Non-Clinical Studies 
MMV533 has previously been evaluated extensively by Sanofi in nonclinical studies as 
compound SAR441121. SAR441121 was acquired by MMV and renamed as ‘MMV533’ 
(short for MMV688533). Refer to the Investigator’s Brochure for further details. 
MMV533 has been shown to act on malarial parasite Ring/Schizont erythrocytic stages, 
and has high potency in vitro with an IC50 of 4-8 nM on a panel of sensitive and resistant 
strains of Plasmodium falciparum, 2.5-21 nM on a panel of field and mutant strains and 
0.8-18 nM on field isolates.   
MMV533 has been shown to be highly efficacious with a single oral dose against 
Plasmodium falciparum in vivo in a severe combined immunodeficiency (SCID) mouse 
model. MMV533 also exhibited an outstanding resistance profile after no mutant selection 
was observed after 6 months of drug pressure.   


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As observed in animals, a high bioavailability of MMV533 is expected in human based 
on the good in vitro permeability (~ 30.10-7cm-1 in standard condition). No major food 
effect is anticipated in human with this compound. In vitro investigations in human 
hepatocytes in primary culture showed MMV533 is very slowly metabolized. Based on 
this experiment, predicted in vivo metabolic clearance values of MMV533 correspond to 
0.6, 1.4 and 1.0% of human hepatic blood flow at 0.1, 1 and 10 μM, respectively. 
Complementary investigation with a model allowing longer incubation time (HepatoPac) 
suggest involvement of CYP3A4 and possibly CYP2D6 at low concentration (0.1µM) in 
the metabolic clearance. MMV533 showed in vitro competitive inhibition of  CYP2B6, 
2C8, 2C9, 2C19, 2D6 with apparent Ki values of 12.6, 0.783, 2.39, 8.99 and 4.04 μM, 
respectively and exhibited time-dependent inhibition of CYP3A with KI and kinact values 
of 28 μM and 0.036 min-1, respectively. Moreover, there is a risk of increase in exposure 
of drug sensitive substrates of these CYP isoforms when co-administered with MMV533. 
This compound was not identified as an inducer of CYP1A1/2, CYP2B6, or CYP3A4. 
Based on allometric scaling and physiologically based pharmacokinetic (PBPK) 
modelling, the predicted t1/2z in humans was approximately 100 hours. 
MMV533 was found to be a P-glycoprotein (P-gP) inhibitor on Caco-2 cell line with 
digoxin as PgP substrate (IC50:108 μM). As such, it cannot be ruled out that co-
administration of MMV533 will affect the pharmacokinetics of a sensitive substrate such 
as digoxin.  
An IC50 of 85.6µM was obtained for MMV533 following vitro bile salt export pump 
(BSEP) inhibition assay. This result suggests that the interaction of MMV533 with BSEP 
at the clinical level is unlikely. 
 
2.2.3 Safety and Risk/Benefit Assessment  
At the time of writing of this protocol, single dose administration of MMV533 is being 
evaluated in the FIH study MMV_MMV533_19_01. Two dose levels, 5 and 10 mg 
MMV533, have been fully evaluated in cohorts of 8 healthy volunteers (6 active drug/2 
placebo). The data, which are currently blinded and preliminary, did not show serious or 
severe AEs nor any clinically concerning events from ECGs, vital signs and safety 
laboratory tests. As shown in Table 4, the 10 mg dose was associated with a group mean 
AUC0-inf, which is 21-fold below the AUC cap identified for the FIH study. 
The risks to the volunteers in this study will be managed by frequent safety monitoring, 
including close monitoring during periods of confinement at the clinical unit when a single 
oral dose of MMV533 will be administered as the investigational medicinal product 
(IMP).  Safety monitoring will include clinical laboratory safety tests (chemistry, 
haematology, serology, urinalysis), physical examination, vital signs and frequent ECG 
analysis. Throughout the study, the safety and PK data will be assessed by the Principal 
Investigator, Sponsor Medical Director and Sponsor Medical Monitor prior to 
commencing the study participation of the next planned cohort.   
See also Section 4.4 for risk management of other study treatments/interventions (non-
IMP).  


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2.3 
RATIONALE 
2.3.1 Rationale for the Study 
MMV533 is being developed for the curative treatment of uncomplicated malaria caused 
by P. falciparum in adults and children as a single dose regimen in a fixed-dose 
combination with another non-artemisinin antimalarial drug.  
One way to expedite the evaluation of novel anti-malarial drugs is to use volunteer 
infection studies (VIS) such as the induced blood stage malaria (IBSM) model.3,4 In the 
IBSM model, healthy volunteers are inoculated with an established master cell bank 
(MCB) of donor red blood cells infected with P. falciparum 3D7. The subsequent 
parasitaemia can be monitored closely and clinically to evaluate the effect of the IMP on 
malaria infection. The IBSM is an attractive tool to test the activity of drugs in nonimmune 
subjects in a rapid and cost-effective manner. The antimalarial activity of a treatment can 
be determined by analysing parasitaemia clearance in subjects after drug treatment by 
quantitative polymerase chain reaction (qPCR).5,6,7  
This study is an IBSM Phase1b study of MMV533 that will be performed in healthy adult 
volunteers with no history of malaria to exclude bias related to previous malarial infection, 
underlying disease or pathological conditions on the safety and PK parameters.  
The study will characterise the effects of single oral doses of MMV533 on the clearance 
of Plasmodium falciparum using the IBSM model in healthy adult volunteers. This study 
will be open-label, and is a well-established method for obtaining useful pharmacokinetic-
pharmacodynamic (PKPD) information on anti-malarial drugs.  
2.3.2 Rationale for the Dose 
A human dose that could maintain blood concentrations above MPC for 100 hours 
(corresponding to 2 parasite erythrocyte cycles) was identified as a target minimal 
efficacious dose for the treatment of acute uncomplicated Plasmodium falciparum 
malaria. Using observed preliminary human PK data from the FIH study (5 and 10 mg 
cohorts) and pharmacodynamic parameters estimated from preclinical studies, the 
predicted efficacious human dose of MMV533 is estimated to be 20 to 35 mg to achieve 
9 log parasite clearance and 25 to 40 mg to achieve 12 log parasite clearance .  
The two doses of MMV533 (single-dose) administered to volunteers enrolled in Cohort 1 
(N=8) of the IBSM model study will be determined based on the safety, tolerability, and 
PK results obtained in the FIH study MMV_MMV533_19_01 and taking into account the 
human efficacious dose predicted from preclinical studies.  
Cohort 1 will be split into two sequential sub-cohorts of 4 participants each: 
• Cohort 1A: the first four participants will receive a single oral dose of MMV533 of 
20 mg.  
• Cohort 1B: the highest dose of MMV533 to be tested in the 4 remaining participants 
enrolled in Cohort 1 will not exceed a dose already tested and deemed to be safe in 
the FIH study, and will not exceed 50 mg (i.e. Cohort 4 of the FIH).  
There will be no safety review in-between cohorts 1A and 1B.  
 
 
 


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Cohorts 2 and 3 will be composed of up to 4 dose groups with a minimum of 2 volunteers 
per dose group. If more than one dose level are tested in a given cohort, volunteers will 
be randomised after inoculation day but prior to Day 8 and administered a single oral dose 
of MMV533. The doses administered to Cohort 2 and Cohort 3 (maximum of 8 dosed 
volunteers per cohort) will be selected based on PK, PD and safety data from the 
preceding cohort and PK and safety data from the FIH study. Prior to inoculation of the 
next cohort, the Safety Review Committee (SRC) will review safety and tolerability data 
up to Day 22 and PK and PD analysis outcomes based on PD and PK data up to Day 15 
from the previous cohort. The maximum dose used in Cohort 2 and 3 will not exceed a 
dose tested and deemed to be safe in the FIH study and will not exceed 200 mg. 
 
 


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3 STUDY OBJECTIVES AND ENDPOINTS 
PRIMARY OBJECTIVES 
PRIMARY ENDPOINTS 
• To characterize the activity of single 
oral doses of MMV533 on clearance 
of Plasmodium falciparum 3D7 
blood stage parasites from the blood 
in an IBSM model 
• Parasite reduction ratio over 48 hours 
(PRR48)8  
• Parasite clearance half-life (Pt½)8  
• Lag phase8 
• Number 
of 
volunteers 
whose 
parasitemia levels fall below the limit 
of quantification (LOQ) following 
treatment with IMP 
• Number 
of 
volunteers 
with 
recrudescence, , defined as ≥5,000 
blood stage parasites/mL after initial 
parasite clearance accompanied by 
either 
a 
two-fold 
parasitaemia 
increase within 48 hours, or re-
occurrence of malaria symptoms with 
a malaria clinical score ≥6. 
• Time to recrudescence defined as the 
time at which asexual parasite levels 
reoccur after being below the LOQ or 
the 
time 
for 
which 
asexual 
parasitaemia levels are minimum, or, 
if not defined, the last observed time 
point without recrudescence 
 
SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
• To characterize the safety and 
tolerability of single oral doses of 
MMV533 administered after IBSM 
challenge 
• Assessment of AEs/TEAEs; two 
phases 
will 
be 
defined: 
one 
corresponding to the inoculation 
phase (ie, 8 days before IMP 
administration), 
and 
one 
corresponding to treatment phase 
(i.e., 
28 
days 
after 
IMP 
administration)  
• Clinical 
laboratory 
evaluations 
including 
haematology, 
biochemistry, 
coagulation, 
urinalysis. 
• Vital signs (body temperature, blood 
pressure and heart rate supine), 
• 12-lead ECG (automatic reading): 
RR, HR, PR, QRS, QT, QTc 
measured by on site-device. 


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SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
• To characterize the pharmacokinetic 
(PK) parameters of single oral doses 
of MMV533 after IBSM challenge 
• Plasma parameters: at least Cmax, tmax, 
AUClast, AUC, t½, CL/F, Vss/F, Vz/F, 
plasma ratios of Cmax, AUClast and 
AUC 
• To 
determine 
the 
relationship 
between MMV533 PK and asexual 
blood-stage parasitaemia in an IBSM 
model 
•  The 
Pharmacokinetics-
Pharmacodynamics 
(PK/PD) 
relationship 
between 
MMV533 
plasma concentrations and blood 
stage asexual parasitaemia will be 
determined 
• Other key parameters will be derived 
from the PKPD model including the 
minimum inhibitory concentration 
(MIC), the minimal parasiticidal 
concentration (MPC90), and the 
parasite reduction rate in 48 h 
(PRR48).  
 
EXPLORATORY OBJECTIVES 
EXPLORATORY ENDPOINTS 
• To investigate drug resistance of P. 
falciparum 3D7 after MMV533 
administration 
 
• Perform in vitro drug sensitivity 
testing 
determining 
the 
50% 
inhibitory concentrations (IC50) and 
the percentage surviving parasites 
 
 
 


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4 INVESTIGATIONAL PLAN 
4.1 
DESCRIPTION OF OVERALL STUDY DESIGN AND PLAN 
The study is a Phase 1b, open label, adaptive study using the Induced Blood Stage Malaria 
(IBSM) model to characterise the antimalarial activity of a single oral dose of the IMP 
MMV533 using pharmacokinetic and pharmacodynamic parameters and to further assess 
the safety and tolerability of MMV533.   
4.1.1 Induced Blood Stage Malaria (IBSM)  
The study is an open label, volunteer infection study (VIS), single dose study in healthy 
malaria-naïve adult volunteers. Up to 3 cohorts of 8 volunteers each will be enrolled in a 
sequential manner, as has been conducted in previous trials and  published.3,4,9,10 The 
study will be initiated before the FIH study MMV_MMV533_19_01 is complete, with 
each dose of MMV533 tested in this study being first considered safe in the FIH study. 
Cohort 1 of this study will test a maximal dose of 50 mg MMV533, while cohort 2 and 3 
will evaluate doses not exceeding 200 mg if this dose is considered safe and tolerable in 
the FIH study. 
The method used for this VIS is the Induced Blood Stage Malaria (IBSM) model, which 
is an established model conducted previously at the clinical site. In the IBSM model, 
volunteers are inoculated with a malaria challenge agent as described in Sections 5.2 and 
5.7.2. 
Study assessments and procedures are as scheduled in Section 1.3 and as described in 
Sections 6 and 7. Briefly, potential volunteers will be screened between Day -36 and Day 
-12, with written informed consent obtained prior to any study procedures and eligibility 
to be assessed according to the inclusion and exclusion criteria. Eligibility will be 
confirmed at the clinical visit between Days -11 and Day -8, with the results of clinical 
safety laboratory tests reviewed at the visit on Day -8 prior to inoculation with the malaria 
challenge agent. Volunteers will be inoculated with the malaria challenge agent on Day -8 
and monitored for a period of at least 60 minutes afterwards. All volunteers attending on 
the same day will be inoculated  within a 60 minute period and within 4 hours of 
preparation of the inoculum. Clinical unit staff will contact volunteers daily on Days -7 to 
-5 to check on well-being and AEs/conmeds. Volunteers may attend the clinical unit for 
an unscheduled safety visit(s) during this period at the discretion of the Principal 
Investigator or delegate.  
Volunteers will attend outpatient visits at the clinical unit on Days -4 to -1 for blood 
sampling for malaria 18S qPCR and safety assessments. Volunteers will be confined to 
the clinical unit from Day -1, and  administered a single oral dose of IMP as per Section 
5.1 on Day 1. Volunteers will be confined for at least 108 hours after IMP dosing for 
safety monitoring, and blood sampling for malaria 18S qPCR and PK analysis. Volunteers 
may be discharged from the clinical unit from 108 hours post-IMP administration if 
considered clinically well by the Principal Investigator or delegate. 
A blood sample for malaria 18S qPCR will be collected at approximately 108 hours post 
MMV533 treatment. Volunteers may then return morning and evening until parasite 
counts are <~500 parasites/mL or at the Investigator’s discretion. Volunteers may then 
have daily visits at the Investigator’s discretion. When parasite counts are <~200 
parasites/mL, sampling may revert to alternate day visits at the Investigator’s discretion. 
Once the malaria 18S qPCR results are negative, or low and stable, volunteers may be 


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reviewed 3 times per week at the Investigator’s discretion until mandatory rescue 
medication (Riamet®) treatment. 
Post-confinement monitoring will be based on parasitaemia results rather than set days, 
particularly if more than 1 dose of MMV533 is administered within a cohort. Visit days 
in Table 3 except for Days 8±2, 14±2, 21±3, 25±3 and EOS are provided as a guide only.  
Outpatient visits will be for continued safety monitoring and blood sampling for PK and 
malaria 18S qPCR.  From Day 5, blood samples may also be taken for qRT-PCR to test 
for presence of gametocytes. 
An approved regimen for malaria treatment will be administered as rescue medication to 
all volunteers beginning on Day 21 (±3 days). Volunteers will be administered Riamet®, 
and also Primacin™ at the discretion of the Investigator if gametocytes are indicated or 
suspected. If an intolerance or contraindication to Riamet® develops or is suspected, 
Malarone® will be administered as rescue medication. Artesunate (IV) may be 
administered if a volunteer is unable to tolerate oral antimalarial treatment with Riamet® 
or Malarone®.  
Rescue treatment may be administered earlier at the discretion of the Investigator, 
including if there is a failure of clearance of parasites or recrudescence. Recrudescence is 
defined as ≥ 5000 blood stage parasites/mL accompanied by either a 2-fold increase 
within 48 hours as measured by malaria 18S qPCR, or reoccurrence of malaria symptoms 
with a malaria clinical score ≥6.  Blood samples will be collected during recrudescence to 
culture parasites in vitro for drug resistance testing. 
Volunteers will attend the end of study visit (EOS) on Day 28 (±3). 
4.2 
DISCUSSION OF STUDY DESIGN INCLUDING CHOICE OF CONTROL 
GROUPS 
The study design is a well-established VIS model, and the clinical site is experienced in 
using the IBSM model to evaluate potential anti-malarial drugs.   
The study is open label to assess the safety and PK of IMP after malaria infection 
respectively. Control groups are not required or appropriate. 
4.3 
SELECTION OF STUDY POPULATION 
The intended patient population for MMV533 is people infected with Plasmodium 
falciparum, but this study will be performed in healthy adult volunteers with no history 
of malaria to exclude any bias related to previous Plasmodium falciparum infection, 
underlying disease or pathological conditions, on the safety and PK parameters. 
4.3.1 Inclusion Criteria 
Volunteers must fulfil all the following inclusion criteria to be eligible to participate in 
the study: 
1. Having given written informed consent prior to undertaking any study-related 
procedure. 
2. Male or female aged between 18 to 55 years inclusive.  
3. Available for the duration of the study and for 2 weeks following the End of Study 
Visit (EOS). 
4. Lives with a spouse, family member, or housemate from the time of inoculation with 
the malaria challenge agent through to the EOS. 


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5. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) 
within the range of 18 to 32 kg/m2 (inclusive). 
6. Willing to defer blood donations to a blood service for a minimum of 6 months after 
the EOS. 
7. Heterosexual women of childbearing potential (WOCBP) must agree to the use of a 
highly effective method of birth control (see below) combined with a barrier 
contraceptive from the screening visit until 30 days after the last dose of the IMP 
(covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose of 
IMP) and have a negative result on urine pregnancy test performed before inoculation 
with the malaria challenge agent.  
Note:  
a. Highly effective birth control methods include: combined (oestrogen and 
progestogen 
containing) 
oral/intravaginal/transdermal/implantable 
hormonal 
contraception 
associated 
with 
inhibition 
of 
ovulation, 
progestogen-only 
oral/injectable/implantable 
hormonal 
contraception 
associated with inhibition of ovulation, intrauterine device, intrauterine 
hormone-releasing system, bilateral tubal occlusion, vasectomised partner, 
or sexual abstinence or same sex relationship. 
b. Female volunteers who are abstinent (from penile-vaginal intercourse) must 
agree to start a double method if they start a sexual relationship with a male 
during the study. Female volunteers must not be planning in vitro fertilisation 
within the required contraception period.  
8. Women of non-childbearing potential (WONCBP) are defined as: 
a. Natural (spontaneous) post-menopausal defined as being amenorrhoeic for at 
least 12 months without an alternative medical cause with a screening follicle 
stimulating hormone level (FSH) >25 IU/L (or at the local laboratory levels for 
post-menopause) 
b. Premenopausal with irreversible surgical sterilization by hysterectomy and/or 
bilateral oophorectomy or salpingectomy at least 6 months before screening (as 
determined by volunteer medical history) 
9. Males who have, or may have female sexual partners of child bearing potential 
during the course of the study must agree to use a double method of contraception 
including condom plus diaphragm, or condom plus intrauterine device, or condom 
plus stable oral/transdermal/injectable/implantable hormonal contraceptive by the 
female partner, from the time of informed consent through to 60 days (covering a 
spermatogenesis cycle) after the last dose of the IMP. Abstinent males must agree to 
start a double method if they begin sexual relationship with a female during the study 
and up to 60 days after the last dose of study drug. Males with female partners of 
child-bearing potential that are surgically sterile, or males who have undergone 
sterilisation and have had testing to confirm the success of the sterilisation, may also 
be included and will not be required to use above described methods of 
contraception. 
10. Vital signs after 5 minutes resting in supine position: 
a. Systolic blood pressure (SBP) - 90–140 mmHg, 
b. Diastolic blood pressure (DBP) - 40–90 mmHg, 
c. Heart rate (HR) 40–100 bpm. 


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11. At Screening and pre-inoculation with the malaria challenge agent: normal standard 
mean of triplicate 12-lead electrocardiogram (ECG) parameters after 10 minutes 
resting in supine position in the following ranges:  
a. QT ≤ 500 msec,  
b. QTcF ≤ 450 msec, QTcB ≤ 450 msec  
c. PR interval ≤ 210 msec for both males and females, and  
d. Normal ECG tracing unless the Principal Investigator or delegate considers an 
ECG tracing abnormality to be not clinically relevant.  
12. In the opinion of the Principal Investigator or delegate, the individual has a high 
probability of adherence with and completion of the study, and willing and able to 
withdraw and refrain from restricted medications. 
13. Certified as healthy by a comprehensive clinical assessment (detailed medical history 
and complete physical examination). 
14. Fluent in English and able to understand and comply with written and verbal 
protocol-related requirements. 
15. Agrees to adhere to the lifestyle considerations throughout the study (see 
Section 4.3.3) and is willing to consume 240 mL full-fat milk with each dose of 
rescue medication Riamet®. 
4.3.2 Exclusion Criteria 
If any of the following exclusion criteria apply, the potential volunteer will not be 
permitted to participate in the study: 
1. Any lifetime history of malaria or participation in a previous malaria challenge study 
or malaria vaccine trial.  
2. Must not have had malaria exposure that is considered significant by the Principal 
Investigator or delegate. This includes but is not limited to:  
- 
history of having travelled to or lived (> 2 weeks) in a malaria-endemic region 
during the past 12 months or planned travel to a malaria-endemic region during 
the course of the trial;  
- 
history of having lived for >1 year in a malaria-endemic region in the past 10 
years;  
- 
history of having ever lived in a malaria-endemic region for more than 10 years 
inclusive. For endemic regions see https://malariaatlas.org/explorer/#/ Bali is not 
considered a malaria-endemic region. 
3. Presence of acute infectious disease and/or abnormal body temperature (defined as 
an a.m. tympanic temperature >37.5 ºC or a p.m. >37.7 ºC) at pre-inoculation. 
4. Haematology, biochemistry or urinalysis results that are outside of the laboratory 
normal reference ranges AND are either: 
- 
considered clinically significant by the Principal Investigator or delegate; OR  
- 
considered not clinically significant by the Principal Investigator or delegate BUT 
ARE ALSO outside of Sponsor-approved clinically acceptable laboratory ranges 
(Appendix 1: Sponsor Approved Clinically Acceptable Inclusion Laboratory 
Ranges) 
NOTE: Volunteers are not excluded if abnormal/out of laboratory normal reference 
range results are considered not clinically significant by the Principal Investigator or 


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delegate AND are within the ranges specified in Appendix 1: Sponsor Approved 
Clinically Acceptable Inclusion Laboratory Ranges. 
5. Breastfeeding or lactating; positive serum pregnancy test at screening, positive urine 
pregnancy test upon admission or at other timepoints as specified by schedule of 
activities tables.  
6. Has previously received a blood transfusion.  
7. Use of antibiotics within 6 weeks of Screening.  
8. Use of systemic therapies with antimalarial activity within 6 weeks of Screening. 
This includes (but not limited to) artemisinin, amodiaquine, atovaquone, 
chloroquine, mefloquine, mepacrine, primaquine, proguanil, quinine, sulfadoxine-
pyrimethamine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, 
clindamycin, doxycycline, and tafenoquine.  
9. Prior to screening and inoculation with the malaria challenge agent:  
• any systemic administration (oral, pulmonary/nasal, IV) of corticosteroids, anti-
inflammatory drugs (excluding commonly used over-the-counter anti-inflammatory 
drugs such as ibuprofen, acetylsalicylic acid, diclofenac), immunomodulators or 
anticoagulants within the past three months. 
• Ibuprofen (preferred) may be used at doses of up to 1.2 g/day, or paracetamol at 
doses of up to 2 g/day after discussion with the Investigator. Limited use of other 
non-prescription medications or dietary supplements, not believed to affect subject 
safety or the overall results of the study, may be permitted on a case-by-case basis 
following approval by the Sponsor in consultation with the Investigator. 
• Any topical administration (cutaneous, eye drops) of corticosteroids  within the past 
2 weeks.  
• Any 
individual 
currently 
receiving 
or 
having 
previously 
received 
immunosuppressive therapy (including systemic steroids, adrenocorticotrophic 
hormone or inhaled steroids) at a dose or duration potentially associated with 
hypothalamic-pituitary-adrenal axis suppression within the past 12 months. 
10. Any contra-indication to rescue medication according to the applicable labelling and 
if found to be severely G6PD deficient at screening (i.e. activity of less than 10% as 
per WHO definition).  
11. Any history or presence of clinically relevant cardiovascular, pulmonary, 
gastrointestinal, hepatic/ gallbladder*/ bile duct, renal, metabolic, haematological, 
neurological, musculoskeletal, rheumatologic,  systemic, ocular, gynaecologic (if 
female), infectious or autoimmune disease, or signs of acute illness. *including 
medical history of asymptomatic gallbladder stones. 
12. History of recurrent headache (eg, tension-type, cluster or migraine) with a frequency 
of ≥2 episodes per month on average and severe enough to require medical therapy. 
History of recurrent nausea and/or vomiting (for vomiting only: more than twice a 
month).  
13. Asthma (excluding childhood asthma, or mild asthma with preventative asthma 
medication required less than monthly and no event requiring treatment in the last 2 
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14. Any personal history of surgical procedures that may affect IMP absorption, 
distribution (i.e. GI surgery) and metabolism or immune response to malaria 
inoculation (splenectomy). 
15. Blood donation of any volume within one month before screening, or participation 
in any research study involving blood sampling (more than 450 mL/unit of blood).   
16. Any documented evidence of current or past cardiovascular disease including:  
• cardiac arrhythmias or  
• family history of congenital long QT syndrome, Brugada syndrome, or 
unexplained sudden cardiac death.  
• Symptomatic postural hypotension at screening irrespective of the decrease in 
blood pressure, or asymptomatic postural hypotension defined as a decrease in 
systolic blood pressure ≥20 mmHg within 3 min when changing from supine to 
standing position.  
17. Has evidence of increased cardiovascular risk (defined as >10%, 5-year risk for those 
greater than 35 years of age, as determined by the Australian Absolute 
Cardiovascular Disease Risk Calculator (http://www.cvdcheck.org.au). Risk factors 
include sex, age, systolic blood pressure (mm/Hg), smoking status, total and High-
density lipoprotein (HDL) cholesterol (mmol/L) and reported diabetes status. Note: 
The site investigator will perform cardiovascular risk calculation once all 
assessments have been performed, prior to eligibility. 
18. History or presence of diagnosed (by an allergist/immunologist) or treated (by a 
physician) food or known drug allergies, or any history of anaphylaxis or other severe 
allergic reactions including face, mouth, or throat swelling or any difficulty 
breathing. Individuals with known lactose or dairy intolerance are excluded. 
Volunteers with seasonal allergies/hay fever or allergy to animals or house dust mite 
that are untreated and asymptomatic at the time of dosing can be enrolled in the trial. 
19. History of convulsion (including drug or vaccine-induced episodes). A medical 
history of a single febrile convulsion during childhood is not an exclusion criterion.  
20. History of substance use disorder(s) within 5 years of screening and/or history of 
alcohol dependancy and/or any prior intravenous use of an illicit substance.  
21. Smoked > 1 pack of cigarettes per day for > 10 years, or who currently (within 14 
days prior to screening) smokes > 5 cigarettes per day.  
22. Any individual who, in the judgement of the Principal Investigator or delegate, is 
likely to be noncompliant during the study, or unable to cooperate because of a 
language problem or poor mental development.  
23. Any individual who cannot be contacted in case of emergency.  
24. Any individual who is the Investigator, or delegates, research assistant, pharmacist, 
study coordinator, project manager, or other staff thereof, directly involved in 
conducting the study.  
25. Any individual without a good peripheral venous access. 
26. Participation in any investigational product study within the 12 weeks preceding 
inoculation with the malaria challenge agent or 5 times the half-life of the 
Investigational product, whichever is longer.  


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27. Positive serology test for hepatitis B (positive HB sAG or anti-HBc Ab), hepatitis C 
(anti-HCV) or human immune deficiency virus (HIV) (positive for anti-HIV1 and 
anti-HIV2 Ab).  
28. Positive urine drug test at Screening,  prior to inoculation with the malaria challenge 
agent or prior to IMP dosing. Any drug from the list of drugs tested (such as 
amphetamine, 
barbiturates, 
benzodiazepines, 
cocaine, 
methamphetamine, 
methadone, Opiates, phencyclidine, Tetrahydrocannabinol; and their metabolites) 
unless there is an acceptable explanation to the Principal Investigator or delegate (eg, 
volunteer has stated in advance that they consumed a prescription of over the counter 
product which contained the detected drug) and/or the volunteer has a negative urine 
drug screen on retest.  
29. Positive alcohol screen at Screening, prior to inoculation with the malaria challenge 
agent or prior to IMP dosing.  
30. Any consumption of citrus fruits (such as grapefruit, Seville oranges) or their juices 
within 7 days prior to IMP administration.    
31. History of serious psychiatric condition that may affect participation in the study or 
preclude compliance with the protocol, including but not limited to: past or present 
psychoses, disorders requiring lithium, a history of attempted or planned suicide, 
more than one previous episode of major depression, any previous single episode of 
major depression lasting for or requiring treatment for more than 6 months, or any 
episode of major depression during the 5 years preceding screening.  
Note: The Beck Depression Inventory will be used as an objective tool for the 
assessment of depression at screening. In addition to the conditions listed above, 
participants with a score of 20 or more on the Beck  Depression Inventory and/or a 
response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) will not 
be eligible for participation. Participants with a Beck score of 17 to 19 may be 
enrolled at the discretion of the Investigator if they do not have a history of the 
psychiatric conditions mentioned in this criterion and their mental state is not 
considered to pose additional risk to the health of the volunteer or to the execution 
of the study and interpretation of the data gathered.  
32. History of malignancy of any organ system (other than localized basal cell carcinoma 
of the skin or in situ cervical cancer considered treated and cured), treated or 
untreated, within 5 years of Screening, regardless of whether there is no evidence of 
local recurrence or metastases.  
33. Any vaccination within 28 days of screening.  
34. Any medical condition that in the opinion of the Principal Investigator or delegate 
would jeopardize the individual’s involvement in the study. 
 
4.3.3 Lifestyle Considerations 
Volunteers will be requested to follow a stable lifestyle while participating in the study, 
with no increased physical activity compared to their usual habits. The volunteers will 
also be requested to adhere to the following restrictions, and should be reminded of them 
throughout the study:  
• Not to consume citrus fruits such as grapefruit or Seville oranges or their juices, 
particularly 7 days prior to IMP administration on Day 1;  


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• Not to consume food or beverages containing quinine, such as tonic water or lemon 
bitter, from the day of inoculation with the malaria challenge agent (Day -8) until 
after rescue medication has completed;  
• Not to consume poppy seeds in the 24 hours prior to screening, day of admission for 
confinement for IMP administration (Day -1) and day of first dose of rescue 
medication;  
• Not to consume food or beverages containing alcohol 24 hours prior to each alcohol 
breath test and for the entire period of confinement at the clinical unit for IMP 
administration (Days -1 to Day 5).  
o Volunteers should not drink more than 2 standard drinks per day from 24 
hours prior to inoculation with the malaria challenge agent on Day -8, and 
after discharge from confinement until the end of treatment with rescue 
medication;  
• Not to consume beverages containing xanthine bases (eg, Red Bull, coffee) during 
the entire period of confinement at the clinical unit for IMP administration (Day -1 
to Day 5).  
o Volunteers should not consume more than 400 mg caffeine per day 
(equivalent to more than 4 cups of coffee) from inoculation with the 
malaria challenge agent on Day -8 until admission for confinement at the 
clinical unit (Day -1), and after being released from confinement at the 
clinical unit on Day 5 until the end of treatment with rescue medication;  
• Not to use tobacco during confinement at the clinical unit for IMP administration 
(Day -1 to Day 5)  
o Volunteers should not smoke more than 5 cigarettes (or equivalent) per 
day until Day -1 and after being discharged from confinement at the 
clinical unit on Day 5 until  the end of treatment rescue medication.  
• Abstain from strenuous exercise sessions for 4 days prior to IMP administration until 
Day 14 post IMP. 
4.3.4 Screen Failures 
Unscheduled visits may be planned to assess, confirm, and follow-up on out-of-range 
clinical laboratory test, vital sign, or ECG values that determine a volunteer’s eligibility. 
A positive urine drug screen should only be re-tested if there is a strong rationale for doing 
so (for example, false positive). The result of the re-test must be considered for volunteer 
eligibility and must be available prior to inoculation with the malaria challenge agent or 
IMP administration. Findings made during unscheduled visits should be reported in the 
source document. 
If a volunteer does not meet all selection criteria (is a screen failure) but at some point in 
the future is expected to meet the eligibility criteria, the volunteer may be rescreened on 
one occasion only. Volunteers who are rescreened will undergo the informed consent 
process, be assigned a new volunteer number, and then restart a new screening phase. 
Minimum information to be collected on screen failures include demography, details of 
the screen failure, eligibility criteria and any SAE. Screen failure information will not be 
entered into the eCRF. Volunteers who fail screening due to an underlying medical 
condition (acute self-limiting viral infections do not apply) previously unknown to them 


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will be reimbursed for their time, and provided with the appropriate referrals for guidance 
and counselling for their condition. 
 
4.3.5 Withdrawal of Volunteers 
Volunteers are free to withdraw from participating in the trial at any time upon request 
and irrespective of the reason. The Principal Investigator or delegate will endeavour to 
obtain the reason for withdrawal and will ask the volunteer to attend an early termination 
visit where safety procedures planned for EOS will be conducted (including PK sample if 
appropriate).   
The Sponsor and/or Principal Investigator or delegate may discontinue or withdraw a 
volunteer from the trial for the following reasons: 
• Pregnancy in a female volunteer (must be withdrawn from the study) 
• Significant non-compliance or major protocol deviation  
• Any clinical AE, laboratory abnormality or other medical condition or situation 
occurs that would not be in the best interest of the volunteer to continue to participate 
in the study (see also Section 4.3.8 for stopping rules)  
• An exclusion criterion newly develops or was not previously recognized that 
precludes the volunteer from continuing to participate in the study;  
• Participating in any other investigational product study while enrolled in this study 
The reason for volunteer discontinuation or withdrawal from the study will be recorded 
on the CRF and withdrawn volunteers will be requested to attend an early termination 
visit (safety procedures are the same as for EOS).   
The Principal Investigator or delegate will continue to provide medical care for any SAEs 
with the volunteer’s permission, until symptoms resolve and/or the volunteer’s condition 
becomes stable.  
4.3.5.1 Withdrawn/discontinued Inoculated Volunteers 
Volunteers who have been inoculated with the malaria challenge agent and wish to 
withdraw or are withdrawn from the trial, must complete anti-malarial rescue treatment 
as described in Section 5.3. Parasitaemia must be confirmed negative by a minimum of 
two negative malaria 18S qPCR tests.  
The Principal Investigator or delegate will demonstrate due diligence in reminding the 
volunteer of the importance of completing anti-malarial treatment and in following up 
with the volunteer to ensure treatment was completed successfully. 
After anti-malarial rescue treatment, the volunteer will be asked to attend an early 
termination visit voluntarily after two negative malaria 18S qPCR tests (safety procedures 
are as described for EOS).   
4.3.5.2 Replacement of Withdrawn/discontinued Volunteers 
Volunteers who have signed the informed consent form but have not received the trial 
intervention (inoculation with the malaria challenge agent) may be replaced. 
The replacement of volunteers who have received any trial intervention (inoculation with 
the malaria challenge agent only or inoculation and IMP) and withdraw or are withdrawn 
or discontinued from the trial, must be discussed between the Principal Investigator and 
the Sponsor.   


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In each cohort, if more than two discontinuations due to non-safety related reasons occur, 
additional subjects may be recruited to replace the discontinued subjects on agreement 
with the study Sponsor. 
4.3.6 Lost to Follow-Up 
The Principal Investigator or delegate will make every effort to contact volunteers who 
fail to return to the clinical site for visits scheduled in the protocol. All efforts must be 
recorded in source document.  
4.3.6.1 Inoculated Volunteers Lost to Follow-up 
For volunteers who have been inoculated with the malaria challenge agent and have not 
received any anti-malarial rescue treatment, follow-up is critical as they will have blood-
stage malarial parasites. A volunteer will be deemed ‘missing’ if they do not reply to 
communication to their personal mobile phone and the nominated contact’s phone number 
for more than 24 hours. The Principal Investigator or delegate will organise a visit to the 
volunteer’s home if they are unable to be contacted for more than 36 hours, and if the 
volunteer is still absent the Principal Investigator or delegate will notify the local police 
for assistance in locating the missing volunteer.  
Once the volunteer has been found and still has parasitaemia, then the volunteer will 
receive rescue treatment as described in Section 5.3 at the Principal Investigator’s or 
delegate’s discretion and in agreement with the Medical Monitor. An ET visit should be 
scheduled after two negative malaria 18S qPCR results as per Section 4.3.5.1.  
4.3.7 Study Discontinuation 
The Sponsor, Principal Investigator, approving HREC, and regulatory authorities 
independently reserve the right to discontinue the trial at any time for safety or other 
reasons. Where practical, this will be done in consultation with the Sponsor and all parties 
notified in writing where applicable. The Sponsor and Principal Investigator will ensure 
that volunteers’ interest and safety are protected, and the Principal Investigator must 
review all volunteers and complete all records as required.  
4.3.8 Trial Intervention/Treatment Discontinuation – Stopping Rules 
The Sponsor, Principal Investigator, approving HREC, and regulatory authorities 
independently reserve the right to discontinue the trial at any time for safety or other 
reasons. Where practical, this will be done in consultation with the Sponsor and all parties 
notified in writing where applicable. The Sponsor and Principal Investigator will ensure 
that volunteers’ interest and safety are protected, and the Principal Investigator must 
review all volunteers and complete all records as required. 
In the event of premature trial termination or suspension, the above-mentioned parties will 
be notified in writing by the terminator/suspender stating the reasons for early termination 
or suspension (with the exception of the Sponsor’s responsibility for notifying the 
Regulatory Authorities). After such a decision, the Sponsor and the Principal Investigator 
will ensure that adequate consideration is given to the protection of the volunteers’ 
interests and safety. The Investigator must review all volunteers as soon as practical and 
complete all required records.  
At study entry and prior to inoculation, a full eligibility check will be performed. 
Volunteers who do not meet the study protocol inclusion/exclusion criteria will not be 
inoculated. 
 


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4.3.8.1 Guidance for Rescue Medication instead of IMP on Day 1 
 
Once inoculated, it is expected that some study participants will experience malaria 
symptoms and biological changes (i.e. mild ALT/AST elevation, mild decrease in 
neutrophil count). Therefore, the following criteria should be considered as guidance for 
the decision not to proceed with IMP dosing on Day 1 and preference for rescue 
medication instead:  
 
1. A volunteer experiences an SAE or ≥Grade 3 event (including inoculum-related 
events such as neutropenia or ALT/AST elevations). 
2. A volunteer with positive alcohol or urine drug screen. 
3. A volunteer with one of the following ECG abnormalities: 
• QTcB or QTcF at any time >480 msec, 
• Bundle branch block (except right bundle branch block that was present prior 
to IMP administration), 
• Any arrhythmia, except: 
a. Sinus bradycardia that is clinically asymptomatic, and not associated with 
any other relevant ECG abnormalities, 
b. sinus tachycardia that is clinically asymptomatic, and not associated with 
any other relevant ECG abnormalities, 
c. Respiratory sinus arrhythmia, 
d. Wandering atrial pacemaker, 
e. Isolated, single premature atrial/ventricular complex (i.e., no bigeminy, 
trigeminy, couplets, triplets or salvos) that does not occur more than once 
in a particular ECG tracing. 
4. The Investigator and delegates may also decide not to proceed with IMP dosing 
based on other safety signals (clinical, ECG, vitals and laboratory tests) not 
included in the above criteria if there is a risk perceived for the study volunteers 
of possibly receiving a subtherapeutic dose of MMV533.  
In each cohort, if more than two discontinuations due to non-safety related reasons occur, 
additional subjects may be recruited to replace the discontinued subjects on agreement 
with the study Sponsor. 
4.3.8.2 Toxicity Criteria and Progression From Cohort 1 to Cohort 2 
For progression from Cohort 1 to Cohort 2, the SRC members will include at least the 
Medical/Project Monitor, the Medical Director, the PI and an infectious diseases 
physician with expertise in malaria (or their delegates). The MMV Project Director or 
further internal or external experts such as a clinical lead and/or a statistician may be 
consulted by the SRT as necessary.  
An SRC meeting is scheduled to occur after completion of Cohort 1  prior to commencing 
Cohort 2. The SRC will review available Cohort 1 safety/tolerability and parasitaemia 
data up to study Day 22 for all inoculated participants in Cohort 1 before enrolment of 
Cohort 2 and determine whether progression to Cohort 2 is indicated. If no safety concerns 
are identified during SRT review, progression to Cohort 2 will take place.  
Initiation of Cohort 2 will be put on hold and further review will be conducted by the 
SRT, if any of the following toxicity criteria are observed in Cohort 1: 
• Inoculum-related or IMP-related SAE; or 


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• any other critical Inoculum-related finding that may place participants at risk within 
the same cohort or in the next cohort; or 
• two or more IMP-related severe (grade 3 or higher), same organ class AEs. 
If after data review the SRC confirms that any of the above has been met, including a 
relationship with the Inoculum and/or IMP, progression to Cohort 2 might not be 
conducted. 
4.4 
RISK/BENEFIT 
ASSESSMENT 
OF 
STUDY 
TREATMENTS 
AND 
INTERVENTIONS OTHER THAN IMP 
4.4.1 Malaria Challenge Agents and the IBSM 
Potential risks to volunteers from inoculation with the malaria challenge agent have been 
identified through review of the literature and previous clinical studies conducted to date 
using the IBSM model with Plasmodium falciparum isolates. Further information can be 
found in the Investigator’s Brochure for the 3D7 malaria challenge agent. 
Briefly, the Plasmodium falciparum 3D7 inoculum has been used to challenge 401 healthy 
volunteers in 32 IBSM Phase 1 clinical trials, 27 of which were successfully undertaken 
at the clinical site (Q-Pharm). Risks include development of mild/moderate symptoms 
associated with malaria infection following the challenge, adverse effects of the IMP and 
adverse effects of the approved malaria rescue medications artemether/lumefantrine 
(Riamet® 20 mg/120 mg), primaquine (Primacin™; if required), Malarone® (if required) 
and artesunate (if required). Risk management of other blood borne infections, transfusion 
reactions, liver function abnormalities and cardiac AEs are outlined below.   
4.4.1.1 Risk management of blood borne infections 
The malaria challenge agent used to inoculate the volunteers contains a very small amount 
of donor blood, however the risk of the volunteer being infected by a possible blood borne 
virus is extremely low due to: 
• The blood donors were screened and tested negative for active blood borne 
infections,  
• White blood cells were removed from the donor blood by the Australian Red Cross 
Blood Service, lowering the risk of infections transmitted by infusion,  
• The volume of blood used in the IBSM model to transmit malaria to the volunteers 
is many thousands of times smaller than the volume of blood used in a blood 
transfusion. 
As part of the safety monitoring for this study, all volunteers will provide a serum safety 
sample before being inoculated with the malaria challenge agent and at the end of study 
visit (EOS). To date, no blood borne infections have been reported in any of the 401 
volunteers who have been inoculated with the P. falciparum 3D7 malaria challenge agent 
in IBSM studies. 
4.4.1.2 Risk management of reaction to the blood sample 
It is possible that volunteers could suffer a transfusion reaction after being inoculated with 
the malaria challenge agent, or develop alloantibodies to the donor red blood cells (RBCs) 
that may make blood transfusion more difficult for that volunteer in the future. The risk 
of developing such alloantibodies is considered extremely low as the donor blood used to 
produce the 3D7 malaria challenge agent was blood group O Rh(D) negative which is 
generally considered to be a ‘universal donor’.  Recipients transfused with such blood are 
considered to have minimal risk of developing RBC alloantibodies, and the volume of 


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blood used in a typical blood transfusion is much larger than that present in the malaria 
challenge agent used in the IBSM model.  To date, one volunteer developed an antibody 
response to a minor Rh antigen (anti-E antibody) after being inoculated with 3D7 malaria 
challenge agent, however there was no laboratory evidence that the donor RBCs in the 
malaria challenge agent provoked production of the alloantibody.  
As part of the safety monitoring for this study, volunteers will be tested for RBC 
alloantibodies at screening and at the end of the study, and will be monitored for signs 
and symptoms of transfusion reactions immediately after being inoculated with the 
malaria challenge agent.  
4.4.1.3 Risk management of malaria infection 
The number of viable blood stage parasites in the malaria challenge agent used to infect 
the volunteers in this study is approximately 2,800. This is substantially lower than the 
approximately 30,000 parasites released into the blood after breaking out of a single liver 
cell after the bite of a single malaria-infected mosquito. In this study, parasite growth and 
malaria symptoms will be closely monitored after volunteers are inoculated with the 
malaria challenge agent.  Parasite growth will be quantitatively measured using 
quantitative polymerase chain reaction (qPCR) to assay for malaria genome copies.  
The IMP will be administered 8 days after inoculation with the malaria challenge agent, 
as this is prior to the time at which advanced clinical symptoms of malaria are likely to 
occur based on the previous clinical trials performed with the 3D7 malaria challenge 
agent. All volunteers will receive compulsory standard anti-malarial treatment by Day 21 
±3, or earlier if required. Refer to the 3D7 Investigator’s Brochure for further information.  
4.4.1.4 Risk management of liver function abnormalities 
Some liver function test (LFT) abnormalities have been reported in volunteers 
participating in IBSM studies:4 
• Transient asymptomatic LFTs including rare cases of alanine aminotransferase 
(ALT)/aspartate aminotransferase (AST) elevations >10 fold the upper limit of 
normal (ULN)  
o No changes in bilirubin reported except in one volunteer with 
unappreciated pre-existing liver disease  
o Did not require treatment and resolved by the end of the studies.  
• LFT elevations were considered as serious adverse events (SAEs) by two Pharma 
sponsors, due to their internal processes for SAE notifications.  
o Following independent review involving drug-induced liver injury 
experts, it was concluded that these LFT elevations in inoculated non-
immune healthy volunteers were most likely due to malaria infection rather 
than caused by an IMP.   
Safety monitoring for this study will include regular safety monitoring to assess for 
asymptomatic LFT abnormalities. Volunteers are required to reduce their consumption of 
possibly hepatotoxic substances (including alcohol and paracetamol) during the study, 
and drugs of abuse are not permitted.  
4.4.1.5 Risk management of cardiac adverse events (AEs) 
To our knowledge, four cardiac SAEs have been reported in healthy volunteers in the 
Netherlands participating in malaria challenge studies using sporozoites (i.e., direct feeds 
by infected mosquitoes rather than IBSM infection). No cardiac SAEs caused by the 
challenge agents have been reported in IBSM studies. However, in a recent study two 


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volunteers (one infected with the P. falciparum 3D7 challenge agent and one infected 
with another malaria challenge agent strain P. falciparum K13) developed ventricular 
extra systoles that were classified as moderate AEs possibly related to malaria. As a 
precaution, people at significant risk of cardiovascular disease will be excluded from 
participating in IBSM studies, and regular safety monitoring including physical 
examination and ECG recordings will take place for all volunteers. Follow-up with a 
cardiologist is also available if any cardiac AEs are seen during the IBSM studies. 
4.4.1.6 Risk/benefit of inoculation with malaria challenge agent  
The clinical study has been designed such that the risk to volunteers in this study will be 
minimized by adequate selection of eligibility criteria (including red blood cells 
alloantibodies tested at screening) and schedule of clinical monitoring, in-house 
observation, and administration and treatment duration. 
There are no direct benefits to the volunteer, however there may be a benefit to society by 
helping to develop future antimalarial therapies.  
4.4.2 Malarial Rescue Medication/s 
Information on the potential risks and adverse effects of rescue medications Riamet®, 
Primacin™, Malarone® and Artesunate can be found in the respective product/consumer 
information documents. To mitigate the potential risks, the wellbeing of volunteers during 
and after administration of rescue treatment will be appropriately monitored. Volunteers 
who have any known contra-indication to any of the rescue medications according to the 
applicable labelling at screening will be excluded from participating in the study.   
5 TRIAL INTERVENTIONS/TREATMENTS 
5.1 
INVESTIGATIONAL MEDICINAL PRODUCT (IMP) 
MMV533 is defined as the IMP for this study. Refer to the Investigator’s Brochure for 
further information. Refer to the Pharmacy Manual for further information on the required 
handling of the IMP.  
Volunteers will be admitted to the clinical unit for oral dosing of the IMP. 
5.1.1 MMV533 
• Volunteers will fast overnight for at least 10 hours.  
• Volunteers will take a single oral dose of IMP with 240 mL of water. The dose of 
IMP will depend on their cohort.  
• Volunteers will then: 
o Be requested to not drink liquids for 1 hour;  
o Remain seated for 10 minutes, then stay in a semi-recumbent position for 
the next 2 hours (except during assessments that require lying positions);  
o Not be permitted food for at least 4 hours.  
• Lunch and dinner will be provided approximately at 5 hours and 12 hours post IMP 
administration, with snacks available between meals. Daily water supply should not 
exceed 3L.  
5.2 
IBSM MODEL MALARIA CHALLENGE AGENT  
The malaria challenge agent is composed of approximately 2800 viable human 
erythrocytes infected with the Plasmodium falciparum 3D7 parasite, and is administered 
intravenously to the volunteer as part of the IBSM model of controlled infection. The 


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infected erythrocytes are from a master cell bank (MCB) that has been well-characterised 
and used in a significant number of IBSM studies. The 3D7 parasite from this MCB is 
sensitive to artemisinin treatment. Refer to the Investigator’s Brochure for the 3D7 
malaria challenge agent for further information.  
Volunteers will attend the clinical unit on the morning of Day -8 to be inoculated with the 
malaria challenge agent as follows: 
• Volunteers may have food until at least 30 minutes prior to inoculation with the 
malaria challenge agent.  
• Volunteers will be cannulated with an appropriate gauge cannula, the placement and 
patency of which will be checked by flushing the vein with clinical grade saline.  
• A single syringe of the prepared malaria challenge agent containing approximately 
2800 viable human erythrocytes infected with P. falciparum 3D7 parasite in 2 mL of 
saline will be injected and the cannula flushed with 5-10 mL of clinical grade saline. 
• The actual number of parasites will take into account the loss of viability resulting 
from cryopreservation, storage and thawing.  
• All volunteers attending on the same day will be inoculated within a 60 minute period 
and within 4 hours of preparation of the malaria challenge agent. The expiry time 
will be listed on the inoculum label.  
• After removal of the cannula, haemostasis will be ensured by use of appropriate 
dressing.  
• Volunteers will remain at the clinical site for at least 60 minutes after inoculation 
with the malaria challenge agent for safety monitoring.  
5.3 
MALARIA RESCUE MEDICATIONS 
All volunteers participating in the study that have been inoculated with the malaria 
challenge agent (including inoculated volunteers who withdraw or are withdrawn from 
the study – see Section 4.3.5.1) will receive mandatory malarial rescue treatment.  
5.3.1 Riamet® (Artemether-lumefantrine) 
Riamet® is a standard treatment for uncomplicated malaria due to P. falciparum in adults. 
A course of Riamet® will be administered to all volunteers who have been inoculated 
with the malaria challenge agent including participants dosed with IMP. The standard 
adult dosing regimen according to the CMI will be used: 4 tablets administered orally 
twice daily over 3 consecutive days (6 doses at 0, 8, 24, 36, 48 and 60 hours, total course 
of 24 tablets). Each dose should be taken with 240 mL full-fat milk.  The first dose of 
Riamet® will be administered to the volunteer at the clinical unit. The remainder of the 
doses will be taken by the volunteer at home and recorded in the diary. Volunteers will be 
given the CMI for Riamet® and reminded of the potential side effects. Clinical staff will 
contact the volunteer on a daily basis during the dosing period to confirm compliance.  
5.3.2 If Gametocytaemia is suspected/confirmed 
The presence of gametocytes (gametocytaemia) will be detected by parasite lifecycle 
stage qRT-PCR performed at the discretion of the Principal Investigator or delegate.  If 
present, PrimacinTM may be administered at the same time as the first dose of Riamet® to 
ensure complete clearance of gametocytes. PrimacinTM is an antimalarial agent containing 
primaquine phosphate and is effective against the sexual forms (gametocytes) of P. 
falciparum, disrupting transmission of the disease by eliminating the reservoir from which 
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Dosing regimen based on G6PD status performed at study entry: 
• If not G6PD deficient - volunteers will take six Primacin® tablets (the total dose 
of 45 mg primaquine) as a single dose with food. 
• If mildly G6PD deficient - volunteers will take two Primacin® tablets (the total 
dose of 15 mg primaquine) as a single dose with food.  
If required, volunteers will be administered  PrimacinTM under supervision at the clinical 
unit. The volunteer will be reminded of the potential side effects of PrimacinTM and given 
the CMI. 
5.3.3 If an Allergy or Contraindication to Riamet® Develops 
Malarone® may be administered at the Principal Investigator’s discretion if an allergy or 
contraindication to Riamet® develops or is suspected. Malarone® is a fixed combination 
product containing atovaquone and proguanil hydrochloride. Atovaquone interferes with 
the biosynthesis of pyrimidines by blocking the parasite mitochondrial electron transport 
chain, and proguanil interferes with the biosynthesis of pyrimidines by inhibiting parasite 
dihydrofolate reductase. 
The treatment course if required will be as recommended by manufacturer for treatment 
of malaria: 
• four tablets of Malarone® (atovaquone 250 mg, proguanil hydrochloride 100 mg) 
once daily orally with food for three consecutive days. 
The first dose of Malarone® will be administered to the volunteer at the clinical unit. 
Volunteers will be given the CMI for Malarone® and reminded of the potential side 
effects. The remainder of the doses will be taken by the volunteer at home and recorded 
in the diary. Clinical staff will contact the volunteer on a daily basis during the dosing 
period to confirm compliance. 
5.3.4 If Volunteer Vomits or Cannot Tolerate Oral Malarial Treatment 
Intravenous artesunate may be used as a rescue medication if the volunteer cannot tolerate 
oral antimalarial rescue treatment (e.g. vomiting). Participants will not be administered 
IV artesunate if vomiting occurs on the second or third day of oral rescue medication.  
Artesunate is an artemisinin derivative and is the recommended parenteral treatment for 
severe malaria in Australia. Artesunate does not have marketing approval in Australia but 
importation is allowed for severe malaria under the Special Access Scheme (SAS).11 The 
Sponsor has sourced artesunate from Guilin Pharmaceutical (Shanghai) Co., Ltd and 
facilitated its importation. The manufacture of the artesunate is undertaken in a WHO Pre-
Qualified GMP facility. Artesunate for IV administration is provided as a powder for 
reconstitution (60 mg artesunic acid) in a vial.  
If required, artesunate will be administered intravenously under medical supervision at a 
dose of 2.4 mg/kg at approximately 0, 12, 24 hours, and then daily for up to seven days 
or until the volunteer is able to take oral drugs.  
5.4 
SELECTION OF DOSE IN THE STUDY  
5.4.1 MMV533 
Up to three doses for each cohort will be selected for a single oral dose of the IMP per 
volunteer to be taken as per Section 5.1.1.  


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Choice of the dose levels will be made cohort by cohort based upon a review of the safety, 
tolerability, and PK data of single dose level cohorts from cohort 1 and from PK and PD 
data from previous cohorts. The SRC will review safety and tolerability data up to Day 
22, and PK and PD analysis outcomes (based on PD and PK data up to Day 15) from the 
previous cohort, prior to inoculation of the next cohort with the malaria challenge agent.  
• Doses tested in Cohort 1:  
o The two doses tested in Cohort 1 will be predicted to cover a sub-curative 
effect (ie, expected to be associated with recrudescence) to allow PK and 
PD parameters to be calculated and the efficacious dose in patients to be 
estimated. This cohort will be split into 2 sequential sub-cohorts of 4 
participants each: 
 Cohort 1A: the first four participants will receive a dose of 
MMV533 of 20 mg.  
 Cohort 1B: the highest dose of MMV533 to be tested in the 4 
remaining participants enrolled in Cohort 1 will not exceed a dose 
tested and deemed to be safe in the FIH study and will not exceed 
50 mg (i.e. Cohort 4 of the FIH study).  
There will be no safety review in-between cohorts 1A and 1B.  
 
• Doses (up to 3) tested in Cohort 2 will depend on the results from Cohort 1: 
o The doses will be chosen so as to refine the estimation of the parameter(s) 
with the greatest uncertainty; that is, high doses will be favoured to 
increase confidence in Emax, and low doses to increase confidence in 
EC50. A range of doses will be considered if both Emax and EC50 have 
similarly large uncertainties. The highest dose of MMV533 to be tested in 
Cohort 2 will not exceed the highest tolerated dose documented in the FIH 
study or 200 mg, whichever is lower. 
o Cohort 3 will proceed if the uncertainty of one or more of the PK and/or 
PD parameters is still large after Cohort 2. The highest dose of MMV533 
to be tested in Cohort 2 will not exceed the highest tolerated dose 
documented in the FIH study or 200 mg, whichever is lower. 
 
5.4.2 Other Study Treatments/Interventions 
The inoculum dose of malaria challenge agent used is as described in the P. falciparum 
3D7 Investigator’s Brochure and is based upon use in the IBSM model in previous clinical 
trials.  
Dose regimens for malarial rescue medications are the standard dosing regimen for adults 
as recommended in their respective product information/CMI.   
5.5 
SELECTION AND TIMING OF DOSE FOR EACH VOLUNTEER 
5.5.1 MMV533 
The SRC will decide the doses of IMP to be used cohort by cohort, except Cohort 1A will 
be administered 20 mg MMV533 as per Section 5.4.1.  
The study is open label. All volunteers will be administered IMP on Day 1 as described 
above in Section 5.1.1, eight days after inoculation with the malaria challenge agent when 


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parasitaemia of all volunteers is expected to be between approximately 5,000 - 25,000 
parasites/mL (unless rescue medication is administered as per Section 4.3.8.1). 
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. IMP 
should not be administered if COVID-19 is suspected (including waiting for test results) 
or confirmed. 
5.5.2 Other Study Treatments/Interventions 
All eligible volunteers will be inoculated with the malaria challenge agent on Day -8 as 
described above in Section 5.2. 
All volunteers inoculated with the malaria challenge agent will receive compulsory 
malarial rescue treatment as described in Section 5.3 on Day 21±3, or earlier under the 
following circumstances: 
• Contraindication to IMP dosing (see Section 4.3.8.1) 
• early withdrawal of inoculated volunteer (see Sections 4.3.5.1 and 5.3) 
• If they experience an inoculum-related serious adverse event (SAE), or 
• If they have a Common Terminology Criteria for Adverse Events (CTCAE) grade 
≥3 AE deemed possibly related to malaria and not self-resolved or relieved with 
concomitant medications, or 
• If after IMP dosing there is failure to clear parasites or recrudescence (see 
Section 6.3.2 for definition), or 
• If the Principal Investigator or delegate considers it necessary for volunteer safety. 
In this situation, the Principal Investigator or delegate will discuss with the Malaria 
Expert and/or the Medical Monitor. However, antimalarial medication may be 
administered prior to consultation if immediate treatment is deemed necessary for 
volunteer safety.  
In these cases, associated safety assessments must continue as per the Detailed Schedule 
of Activities for rescue medication in Table 3 and malaria clinical score and malaria 18S 
qPCR must be continued for up to a minimum of 72 hours after the first dose of malaria 
rescue medication. 
The Principal Investigator or delegate must record the reasons for any administration of 
rescue medication prior to Day 21±3 in source document. 
5.6 
DOSE INTERRUPTIONS AND REDUCTIONS  
Dose interruptions per volunteer are not applicable to the IMP as it will be administered 
in a single dose. Dose adjustments will be made as outlined above in Section 5.4 and as 
recommended on an ongoing basis cohort by cohort by the SRC.  
If required, Primacin® dose may be reduced as described above in Section 5.3.2. 
5.7 
SUPPLY, PACKAGING AND LABELLING OF STUDY TREATMENTS 
The IMP and other study medications/interventions (non-IMP) will be manufactured and 
packaged according to Good Manufacturing Practice (GMP), all local regulations and 
labelled for clinical trial use in accordance with Australian requirements including Annex 
13 of GMP. The IMP will be supplied to the clinical unit with an acknowledgement of 
receipt form.  


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5.7.1 MMV533 
MMV533 is supplied by Piramal (Pharmaceutical Development Services, Piramal 
Enterprises Ltd. Ahmedabad) and is stored at PCI Pharma Services, Port Melbourne 
prior to delivery to site.  
 
MMV533 will be provided to site as film-coated tablets in two strengths: 5 mg and 50 
mg (identical in shape and size). The tablets are white to off-white, round, biconvex, 
film-coated tablets. 
5.7.2 Malaria Challenge Agent 
The P. falciparum 3D7 MCB was produced from an individual with blood group ORh(D) 
negative who was infected with the parasite by mosquito bite. The 3D7 MCB was 
cryopreserved, aliquoted into cryovials, and is stored in liquid nitrogen under controlled 
conditions at QIMR Berghofer.  
On the day of inoculation, the malaria challenge agent will be prepared aseptically from 
a frozen cryovial of the P. falciparum 3D7 MCB at QIMR. Preparation includes thawing, 
washing and resuspending the infected red blood cells in saline to a final volume of 2 mL, 
and the malaria challenge agent will then be supplied without delay to the clinical unit as 
single doses in syringes. The syringes will be labelled in accordance with GCP guidelines 
and local regulatory requirements, including the expiry time for use. All volunteers should 
be inoculated prior to the expiry of the malaria challenge agent (within 4 hours of 
preparation; expiry time will be listed on inoculum label).  
5.7.3 Malarial rescue medications 
Riamet®, Malarone®, and Primacin™ will be sourced and provided by the clinical unit: 
• Riamet® will be supplied as tablets containing 20 mg arthemether and 120 mg 
lumefantrine.  
• Malarone® will be supplied as tablets containing 250 mg atovaquone and 100 mg 
proguanil hydrochloride.  
• Primacin™ will be supplied as tablets containing 13.2 mg primaquine phosphate 
equivalent to 7.5 mg primaquine. 
• Artesunate for intravenous administration is provided as a powder (60 mg artesunic 
acid) for reconstitution in a vial. 
5.8 
STORAGE OF STUDY TREATMENTS 
Prior to dispensing, the IMP and malarial rescue treatments must be stored in a secure and 
locked storage area with limited access, and under monitored, temperature controlled 
conditions as appropriate. All storage requirements are detailed in the respective 
Investigator Brochures or product information/CMI. 
The Principal Investigator or delegate (e.g. clinical unit Pharmacist) will be responsible 
for the correct storage and handling of IMP and rescue medications, and for the malaria 
challenge agent when received on the day of use. Deviations from the storage 
requirements, including corrective action, must be documented. Refer to the Pharmacy 
Manual for further information.  
5.9 
ACCOUNTABILITY, RECONCILIATION AND RETURN OF THE STUDY 
TREATMENTS 
The Principal Investigator will ensure that the IMP, malaria challenge agents and malarial 
rescue medication/s are dispensed only to eligible volunteers enrolled in this study and 


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will ensure that complete and current dispensing and inventory records are maintained. 
The site’s dispensing logs must record every episode of dispensing of the IMP, malaria 
challenge agent and malarial rescue medication/s.   
The logs must contain the following information: 
• Date of receipt. 
• Number of tablets / syringes / vials received. 
• Batch number(s). 
• The identification of the volunteer to whom the tablets / syringes / vials was 
dispensed. 
• The date(s), time and quantity dispensed to the volunteer. 
• The cumulative total of malaria challenge agents, IMP and rescue medication at 
site. 
• Tablets / syringes / vials damaged, destroyed, or returned. 
Supplies of the IMP will be shipped to the clinical unit prior to study start. The study 
monitor will perform drug accountability during routine monitoring visits.  The malaria 
challenge agent will be provided to the clinical unit on the day of inoculation as required.  
Once the study has completed or has been discontinued, final accountability and 
reconciliation will be performed. Any discrepancies will be investigated and the 
resolution documented.  All full, partially full, and empty containers of IMP and other 
medication must be returned to the Pharmacy, Manufacturer or Sponsor for destruction, 
and the appropriate form sent to the Sponsor. Any remaining unused malaria challenge 
agent will be discarded as per approved standard operating procedures.  
Please refer to the Pharmacy Manual for further details on the storage, handling, and 
dispensing of IMPs, malaria challenge agents and rescue medications. 
5.10 PROHIBITED CONCOMITANT THERAPY 
Any medication that is exclusionary for eligibility at Screening remains prohibited during 
the study. Volunteers will be requested to refrain from taking non-approved concomitant 
medications during their participation in the study. 
Ibuprofen may be permitted for use at doses up to 1.2 g/day or paracetamol at doses up to 
2 g/day only after the volunteers discusses with the Principal Investigator or delegate. 
Ibuprofen is the preferred treatment, however paracetamol may be used if ibuprofen does 
not relieve the volunteer’s symptoms. Acetyl salicylic acid and/or diclofenac may also be 
permitted after discussion with the Principal Investigator or delegate. Contraceptives are 
permitted. 
The use of any concomitant medication other than ibuprofen, paracetamol, acetyl salicylic 
acid or diclofenac as described above will only be permitted if specified in the inclusion 
criteria, study procedures (such as malaria rescue treatment) or otherwise required 
medically. Any concomitant use of medications other than study-specific treatments 
should be recorded by the volunteer in the diary card.   
Any use of concomitant medication including name of medication, daily dosage and 
duration of use must be recorded by study staff in source documents and in the eCRF.  
5.11 TREATMENT COMPLIANCE  
Volunteers will be administered a single oral dose of IMP under medical supervision 
while confined at the clinical unit. Volunteers will be inoculated with the malaria 


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challenge agent by clinical unit study staff while attending the clinical unit. Treatment 
compliance for volunteers administered malarial rescue medication is described in Section 
5.3 above. 
5.12 MEASURES TO MINIMIZE BIAS 
5.12.1 Randomisation Procedures 
The study is open label and randomised. Each cohort will be composed of up to 3 dose 
groups with a minimum of 2 subjects per dose group. If more than one dose level are 
tested in a given cohort, subjects will be randomised after inoculation day but prior to Day 
8 and administered a single oral dose of MMV533. The randomisation schedule will be 
generated by a statistician using a validated system as described in a Randomisation Plan 
and/or Randomisation Procedure. 
6 STUDY ASSESSMENTS AND PROCEDURES  
6.1 
STUDY CONDUCT SCHEDULE 
The schedules for all assessments and study activities are summarised in the Schedule of 
Activities and shown in more detail in the Detailed Schedule of Activities in Section 1.3. 
All study assessments and procedures are as described in Section 6.2, 6.3 and Section 7. 
Protocol waivers or exemptions are not permitted. 
6.1.1 Screening 
The screening period for the study will be 25 days from Day -36 to Day -12. During this 
time, the volunteer will sign the patient information consent form (PICF) prior to any 
study-related procedures or assessments and eligibility will be assessed (see Schedule of 
Activities Table 1). 
Demographics and comprehensive medical history will be documented at screening. 
6.1.2 Inclusion/Eligibility Visit  
Eligibility must be confirmed prior to inoculation with the malaria challenge agent on 
Day -8.  
The volunteer will attend the clinical unit at least once between Days -11 to -9 in order to 
assess eligibility criteria that require substantial time for results prior to inoculation with 
the malaria challenge agent.  
Samples for clinical laboratory testing will be obtained at this visit to ensure results are 
available prior to inoculation on Day -8. A second visit is permitted if reassessment is 
required to confirm eligibility prior to inoculation.  
Only one re-test of any baseline parameter is permitted, and the result must be available 
for review prior inoculation with the malaria challenge agent.  
In addition, the following will be performed: 
• Any new medical conditions, illnesses and concomitant medications since screening 
should be checked for and recorded.  
• Symptom-directed physical examination will be performed if required.  
• Body weight will be re-checked.  
• Only if participant has consented to optional QIMR study as per Section 7.6: collect 
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For each cohort, eligible additional volunteers may be available as back-up, in the event 
planned cohort volunteers withdraw or are withdrawn prior to inoculation with the malaria 
challenge agent.   
Volunteers who meet all of the inclusion criteria and none of the exclusion criteria will be 
eligible for inclusion into the study and to be inoculated with the malaria challenge agent 
on Day -8.  Volunteers will be reminded of the lifestyle considerations for the duration of 
the study (see Section 4.3.3).  
6.1.3 Day -8 Inoculation with Malaria Challenge Agent 
Volunteers will attend the clinical unit on the morning of Day -8 to be inoculated with the 
malaria challenge agent. The Principal Investigator or delegate will review all eligibility 
information for each volunteer prior to inoculation with the malaria challenge agent, 
including review of clinical laboratory safety tests performed at the inclusion/eligibility 
visit (see Section 6.1.2) and assessments conducted pre-inoculation on Day -8.  
For each cohort, eligible additional volunteers may be available as back-up, in the event 
planned cohort volunteers withdraw or are withdrawn prior to inoculation with the malaria 
challenge agent. 
The Principal Investigator or delegate will emphasise to the volunteer the importance of 
returning to the clinical unit for IMP administration and subsequent mandatory malaria 
rescue treatment after inoculation with the malaria challenge agent. The volunteer will be 
asked to confirm that they will not be living alone from Day -8 until EOS and to re-
confirm the contact details of housemates recorded at the screening visit.  
The following will be performed prior to inoculation with the malaria challenge agent: 
• Check for and record any new medical conditions, illnesses and concomitant 
medications since screening and eligibility visit,  
• Alcohol breath test and urine drug screen,   
• Symptom-directed physical examination if required,  
• Vital signs and body temperature,  
• Triplicate 12-lead ECG,  
• Cannulate volunteer with indwelling intravenous cannula into peripheral vein of 
volunteer’s forearm to obtain  blood samples and administer the malaria challenge 
agent (record which arm used),  
• Calculate malaria clinical score, 
• Collect blood samples for malaria 18S qPCR, inoculum-related safety serum sample 
and IMP safety serum sample.   
• Confirm eligibility. 
The volunteer will be inoculated with the malaria challenge agent as described in Section 
5.2. 
The following will be performed after the volunteer is inoculated with the malaria 
challenge agent: 
• Monitor the volunteer for at least 60 minutes after inoculation to check for immediate 
adverse reactions, and record any AEs and/or concomitant medications, 
• Educate volunteers on the signs and symptoms of malaria (see Appendix 2: Malaria 
Clinical Score);   


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• Inform volunteers that they should immediately contact the Principal Investigator or 
delegate if they experience any unexpected symptom, effect or event and that they 
can contact the clinical unit by telephone 24 hours a day, and:  
• Provide volunteer with a volunteer card listing the study number and appropriate 
clinical unit telephone contact details. The volunteer must also provide telephone 
contact details so that they can be contacted in an emergency. 
• Emphasise to volunteers the importance of returning to the clinical unit on the 
nominated day (Day -1) or as advised by the clinical unit staff, for IMP 
administration as antimalarial treatment,  
• Issue diary card and thermometer to volunteers to collect information during 
outpatient periods including oral temperature (if required), symptoms of malaria,  
and details of daily physical activity and alcohol consumption. Volunteers will bring 
their diary cards to each visit to the clinical trial unit for review. Site staff will enter 
the diary information into the eCRF.  
• Measure vital signs approximately 60 minutes after inoculation with the malaria 
challenge agent and prior to leaving the clinical unit.  
• Calculate malaria clinical score prior to leaving the clinical unit. 
6.1.4 Days -7 to -5 Malaria monitoring by phone 
Volunteers are expected to be asymptomatic from Days -8 to -5. Clinical unit staff will 
ring or text message the volunteer daily to monitor well-being and solicit AE information. 
Details of this contact will be recorded in the source document.  
Volunteers will attend the clinical unit if any AEs are reported during this period involving 
assessments of vital signs, body temperature, 12-Lead ECG, symptom directed physical 
examination, malaria clinical score and possible blood sampling for 18S qPCR. 
After inoculation with the malaria challenge agent, participants may develop symptoms 
of malaria (e.g. fever) that are also symptoms of COVID-19. The risk of COVID-19 is 
currently low in Queensland. However, the Investigator will consider the possibility of 
COVID-19 when unexpected symptoms (e.g. sore throat, anosmia, cough/respiratory 
symptoms) are reported along with fever. The Investigator will review all symptoms, their 
timing with respect to date of inoculation, 18S qPCR results and other available 
information to decide if symptoms can be confidently attributed to malaria/inoculation. If 
the symptoms are considered consistent with malaria/inoculation, and at the discretion of 
the Investigator, the site standard procedures for participants with COVID-19 symptoms 
will not be required. This decision will be documented in source notes by the Investigator. 
However, if considered appropriate or necessary by the Investigator, the participant may 
be isolated at the clinical unit for COVID-19 testing and quarantine as per site procedure, 
and to ensure safety monitoring for malaria is performed as per protocol. 
6.1.5 Day -4 until Day -1 Outpatient Visits 
NOTE for consideration of COVID-19 symptoms: After inoculation with the malaria 
challenge agent, participants may develop symptoms of malaria (e.g. fever) that are also 
symptoms of COVID-19. The risk of COVID-19 is currently low in Queensland. 
However, the Investigator will consider the possibility of COVID-19 when unexpected 
symptoms (e.g. sore throat, anosmia, cough/respiratory symptoms) are reported along 
with fever. The Investigator will review all symptoms, their timing with respect to date of 
inoculation, 18S qPCR results and other available information to decide if symptoms can 
be confidently attributed to malaria/inoculation. If the symptoms are considered 
consistent with malaria/inoculation, and at the discretion of the Investigator, the site 


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standard procedures for participants with COVID-19 symptoms will not be required. This 
decision will be documented in source notes by the Investigator. However, if considered 
appropriate or necessary by the Investigator, the participant may be isolated at the clinical 
unit for COVID-19 testing and quarantine as per site procedure, and to ensure safety 
monitoring for malaria is performed as per protocol. 
Volunteers will attend the clinical unit for outpatient monitoring visits once (in the 
morning) on Day -4 and twice daily on Days -2 and -3 (separated by 12±2 hours on each 
day). The following procedures will be performed: 
• Symptom-directed physical examination when signs or symptoms malaria are 
identified and it is clinically indicated (once daily only),  
• Elicit information on AEs and concomitant medications and review diary card,  
• Vital signs and body temperature, 
• Standard 12-lead ECG on Day -1 morning only, 
• Collect blood samples for LFTs only on Day -3, 
• Calculate malaria clinical score,  
• Collect blood sample for malaria 18S qPCR. 
Prior to IMP dosing, the Investigator and/or delegates should ensure that no 
contraindication to administration of IMP are present as described in Section 4.3.8 (in 
which case, rescue medication should be administered instead of IMP). 
6.1.6 Day -1 to Day 5 Confinement for IMP administration 
Volunteers will be admitted to the clinical unit in the morning of Day -1 for confinement 
and observation for at least 108 hours after IMP administration. Parasitaemia is expected 
to be approximately between 5,000 and 25,000 parasites/mL.  
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. IMP 
should not be administered if COVID-19 is suspected (including waiting for test results) 
or confirmed. 
Admission procedures on Day -1: 
• Symptom-directed physical examination  
• Alcohol breath test and urine drug screen  
• Review diary temperature card and elicit information on AEs and concomitant 
medications  
• Vital signs and body temperature  
• Cannulate volunteers with indwelling intravenous cannula into peripheral vein of the 
volunteer’s forearm to obtain blood samples (the cannula will be locked with a 
mandrel between blood samples).  
• Collect blood samples for haematology and biochemistry on Day -1 morning. NOTE: 
the results of this safety testing must be available for review prior to IMP 
administration on Day 1,  
• Collect urine sample for urinalysis Day -1 morning, NOTE: the results of the Day -
1 sample must be available for review prior to IMP administration on Day 1; 
• Calculate malaria clinical score  
• Collect blood sample for malaria 18S qPCR AM and PM (parasite clearance baseline 
sample) 


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Day 1 Pre-dose activities: 
• Vital signs supine  
• 12-lead ECG  
• Body temperature  
• Blood samples for:  
o haematology, biochemistry  
o PK sample  
o Malaria 18S qPCR  
o Only if participant has consented to optional QIMR study as per Section 
7.6: collect blood sample for QIMR research serum samples 
• Urine sample for urinalysis  
• Malaria clinical score  
The volunteer will be administered IMP on Day 1 as described in Section 5.1.1.  
After administration of IMP, the following will be conducted:  
• Follow up volunteers as inpatients for at least 108 hours after IMP administration to 
monitor safety, tolerability and adequate clinical response of the IMP treatment,  
• Symptom-directed physical examination if signs or symptoms of malaria are 
identified and it is clinically indicated,  
• Vital signs and body temperature at timepoints defined in the Detailed Schedule of 
Activities in Table 2 and Table 3 and as per Section 7.2,  
• Standard 12-lead ECG at timepoints defined in the Detailed Schedule of Activities 
in Table 2 and Table 3 and as per Section 7.3,  
• At timepoints defined in the Detailed Schedule of Activities in Table 2 and Table 3, 
collect blood samples for  
o clinical laboratory safety tests (Section 7.5.1) 
o PK analysis (Section 6.4) 
o Malaria 18S qPCR (Section 6.2.1)  
• Collect urine for urinalysis at timepoints defined in the Detailed Schedule of 
Activities in Table 2 and Table 3 and Section 7.5.6.  
• Calculate malaria clinical score at timepoints defined in the Detailed Schedule of 
Activities in Table 2 and Table 3 and Section 7.4.  
• Record AEs and concomitant medications. 
Before discharge at least 108 hours post-dose, the following will be conducted: 
• Symptom-directed physical examination if required. Before discharge, the clinical 
unit staff must confirm with the Principal Investigator or delegate if any volunteer 
requires symptom-directed physical examination.  
• Vital signs and body temperature,  
• Collect blood samples for  
o Malaria 18S qPCR  
o qRT-PCR pfs25 at the discretion of the Principal Investigator or delegate 
(Section 6.2.1   
• Calculate malaria clinical score 
• Record AEs and concomitant medications 


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Volunteers will be permitted to leave the clinical unit 108 hours after IMP administration 
at the discretion of the Principal Investigator or delegate if:  
• they are asymptomatic,  
• have normal physical examination if a symptom directed physical examination was 
required,  
• no clinically significant laboratory abnormalities. 
6.1.7 Post-confinement Outpatient Monitoring Visits 
 
After discharge from the clinical unit, volunteers should return morning and evening 
(approximately 12 hours apart) until parasite counts are <~500 parasites/mL or at the 
Investigator’s discretion. Volunteers may then have daily visits at the Investigator’s 
discretion. When parasite counts are <~200 parasites/mL, sampling may revert to alternate 
day visits at the Investigator’s discretion. Once the malaria 18S qPCR results are negative, 
or low and stable, volunteers may be reviewed 3 times per week at the Investigator’s 
discretion until treatment with rescue medication. 
The following procedures will be conducted at each outpatient visit:  
• Review diary temperature card, record AEs and concomitant medications,  
• Symptom-directed physical examination if signs and symptoms of malaria are 
identified and it is clinically indicated,  
• Vital signs and body temperature,  
• Collect blood samples for malaria 18S qPCR (Section 6.2.1) on a daily basis in the 
morning or twice daily depending on parasite count or at the discretion of the 
Principal Investigator or delegate, 
• Collect blood sample for qRT-PCR pfs25 at the discretion of the Principal 
Investigator or delegate (Section 6.3.1), 
• Collect blood samples for parasite drug resistance analysis at the discretion of the 
Principal Investigator or delegate (Section 6.3.2). 
• Calculate malaria clinical score while malaria counts are positive or at the discretion 
of the Principal Investigator or delegate (Section 7.4). 
Outpatient visits are required at the timepoints defined in the SOA Table 3 and relevant 
sections when required for the following: 
• Standard 12-lead ECG (Section 7.3)  
• Collect blood samples for  
o clinical laboratory safety tests (Section 7.5.1) 
o PK analysis (Section 6.4) 
• Collect urine for urinalysis at timepoints (Section 7.5.6).  
• Only if participant has consented to optional QIMR study as per Section 7.6: collect 
blood sample for QIMR research serum samples (see SOA Table 3) 
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. 
6.1.8 Mandatory Malaria Rescue Medication  
All volunteers will attend the clinical unit on Day 21±3 to begin mandatory malaria rescue 
medication as described in Section 5.3. Malaria rescue medication may be administered 
earlier as described in Section 5.5.2. In these cases, associated safety assessments must 
continue as per the Detailed Schedule of Activities for rescue medication in Table 3 and 


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malaria clinical score and malaria 18S qPCR must be continued for up to a minimum of 
72 hours after the first dose of malaria rescue medication.  
Volunteers should take at least the first dose of rescue treatment under supervision at the 
clinical unit, and may take the remaining doses (if applicable) at home as determined by 
the Principal Investigator or delegate. Clinical unit staff will contact the volunteers on a 
daily basis to ensure compliance with the malaria rescue medication dosing regimen and 
to check well-being.  
The following procedures will be performed prior to the first dose of malaria rescue 
medication: 
• Review diary card, record AEs and concomitant medications,  
• Symptom-directed physical examination, 
• Alcohol breath test and urine drug screen,  
• Vital signs and body temperature,  
• Standard 12-lead ECG,  
• Collect blood samples for  
o clinical laboratory safety tests  
o PK analysis (Section 6.4)  
o Serology (Section 7.5.3) 
o Red blood cell alloantibodies  
o Malaria 18S qPCR  
o qRT-PCR pfs25 (if required) 
• Calculate malaria clinical score while malaria counts are positive or at the discretion 
of the Principal Investigator or delegate. 
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. 
6.1.9 Unscheduled Monitoring Outpatient Visits 
Volunteers may attend unscheduled visits at the clinical unit for malaria 18S qPCR or 
safety monitoring if required and at the discretion of the Principal Investigator or delegate, 
based on parasitaemia, clinical symptoms and/or clinical laboratory safety test results. The 
clinical site staff will contact the volunteer by phone to arrange these visits. Unscheduled 
visits will be recorded in source document and in the eCRF.  
6.1.10 Day 28±3 EOS 
Volunteers will attend the clinical unit for the EOS only after completion of malaria rescue 
medication and 2 negative malaria 18S qPCR results. The following procedures will be 
conducted: 
• Review diary card and record AEs and concomitant medications  
• Full physical examination  
• Vital signs and body temperature  
• Standard 12-lead ECG  
• Collect blood samples for  
o clinical laboratory safety tests – may include CRP at the discretion of the 
Principal Investigator or delegate (Section 7.5.1) 
o Serology (Section 7.5.3) 
o Red blood cell alloantibodies  
o Malaria 18S qPCR  
o PK analysis (Section 6.4)  


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o qRT-PCR if required  
o Inoculum-related Safety serum sample and IMP safety serum sample  
o Only if participant has consented to optional QIMR study as per Section 
7.6: collect blood sample for QIMR research serum samples 
• Collect urine for urinalysis 
• Calculate malaria clinical score if malaria counts are positive or at the discretion of 
the Principal Investigator or delegate. 
If a volunteer still has unresolved symptoms or abnormal clinical laboratory results at the 
EOS, the Principal Investigator or delegate may ask them to return to the clinical site for 
appropriate follow-up until resolution.  
6.2 
PHARMACODYNAMIC PRIMARY ASSESSMENT 
6.2.1 Malaria 18S qPCR 
The presence and measurement of total malaria parasites in blood of volunteers 
participating in IBSM model will be determined by quantitative real-time polymerase 
chain reaction targeting the malarial 18S rRNA gene (referred to as malaria 18s qPCR). 
Malaria 18S qPCR is expressed as parasites/mL and will be used to determine primary 
endpoints including parasite reduction ratio over 48 hours (PRR48), parasite clearance 
half-life (Pt1/2), lag phase, number of volunteers whose parasitaemia fall below LOQ 
following administration of IMP, number of volunteers with recrudescence and time to 
recrudescence.  
Malaria 18S qPCR will also be used to monitor the parasitaemia of volunteers in real time, 
in order to monitor safety and to decide if mandatory anti-malarial rescue treatment is 
required earlier than the scheduled Day 21±3.   
As detailed in the Detailed Schedule of Activities Table 2 blood will be collected from 
volunteers to determine malaria 18S qPCR on Day -8 prior to inoculation with the malaria 
challenge agent, Day -4, then twice daily on Day -3, Day -2 and Day -1 at the discretion 
of the Principal Investigator or delegate. On Day 1, blood will be collected pre-IMP 
administration, then at the following hours post-IMP administration while confined in the 
clinical unit: 2, 4, 6, 8, 12, 16, 20, 24, 30, 36, 48, 60, 72, 84, 96 and 108 hours post-IMP 
administration. Time windows during confinement are as per Table 5. 
Volunteers may then return morning and evening for malaria 18S qPCR sampling until 
parasite counts are <~500 parasites/mL or at the Investigator’s discretion. Volunteers may 
then have daily visits for malaria 18S qPCR sampling at the Investigator’s discretion. 
When parasite counts are <~200 parasites/mL, malaria 18S qPCR sampling may revert to 
alternate day visits at the Investigator’s discretion. Once the malaria 18S qPCR results are 
negative, or low and stable, volunteers may be reviewed 3 times per week at the 
Investigator’s discretion until mandatory treatment with rescue medication scheduled for 
Day 21±3. 
In the case of anti-malarial rescue medication being required before Day 21±3, associated 
safety assessments including the Malaria Clinical Score must be continued as per the 
Detailed Schedule of Activities for rescue medication in Table 3 and must be performed 
at a minimum 72 hours after rescue treatment was completed.   
After rescue medication has been commenced, a minimum of 2 negative 18S qPCR results 
are required prior to the EOS.  
Further information may be found in the Laboratory Manual.  


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6.3 
OTHER PHARMACODYNAMIC PARAMETERS 
6.3.1 pfs25 qRT-PCR  
Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) tests for the 
malarial gametocyte-specific mRNA transcript pfs25.  
Bloods samples for qRT-PCR will be collected from Day 5 onwards if malaria 18S qPCR 
results suggest the presence of gametocytes in the volunteers’ blood and/or at the 
discretion of the Principal Investigator or delegate.  
6.3.2 Parasite Drug Resistance 
Blood samples will be collected from volunteers if they experience recrudescence.  
Parasite recrudescence is defined as ≥5,000 blood stage parasites/mL after initial parasite 
clearance accompanied by either a two-fold parasitaemia increase within 48 hours, or re-
occurrence of malaria symptoms with a malaria clinical score ≥6. 
Malarial parasites will be obtained from the samples and analysed to determine resistance 
to MMV533 and investigate molecular mechanisms responsible for resistance. Parasite 
drug resistance will be assessed by calculating the IC50 of IMP and determining the 
percentage of surviving parasites using in vitro drug sensitivity testing. 
Samples may be shipped to a national or international reference laboratory for phenotypic 
assessment and parasite gene sequencing analysis. Further information on sampling may 
be found in the Laboratory Manual.  
6.4 
PHARMACOKINETICS 
Blood sample handling for PK analysis is described in the Laboratory Manual. Exact time 
of PK sampling is to be respected and the actual time of sampling recorded in source 
document and into the eCRF.  
Blood samples will be collected for PK analysis at the following timepoints: 
• Day 1 pre-IMP administration; 
• At the following hours post-IMP administration:  
o 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10.0, 12, 24, 48 72 and 96 hours;  
o Day 8 (168 hours), Day 14 (312 hours), Day 21 (480 hours) and EOS Day 
28 (648 hours).  
The permitted time windows for PK blood sampling are detailed in Table 5. 
 
 


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Table 5: Permitted PK and PD Blood Sampling Time Windows 
Time point  
Tolerance window 
Pharmacokinetic/Pharmacodynamic Blood Samples 
In confinement 
Pre-dose  
Within 120 min  prior to IMP dosing 
0.5-4 hours inclusive after IMP administration  
± 15 min 
6-12 hours inclusive after IMP administration  
± 60 min 
24-96 hours inclusive after IMP administration  
± 120 min 
Post-confinement Outpatient Visits 
Days 8, 14 
± 2 days 
Day 21, EOS  
± 3 days 
7 SAFETY ASSESSMENTS 
• The schedules for all safety assessments/activities are summarised in the Schedule 
of Activities (Table 1) and in more detail in the Detailed Schedule of Activities 
(Table 2 and Table 3). Protocol waivers or exemptions are not permitted.   
• All safety assessments may be conducted at unscheduled visits or timepoints if 
required for the volunteer’s safety at the discretion of the Principal Investigator or 
delegate.  
• When several assessments/activities are scheduled to take place at the same 
timepoint, the order is recommended to be: ECG, vital signs, blood sampling, IMP 
administration, meal (where applicable/appropriate), urine sampling.  
• Exact timing for PK blood sampling is to be maintained – safety 
assessments/activities scheduled for these timepoints will be conducted ahead of the 
timepoint. 
7.1 
PHYSICAL EXAMINATION 
Physical examination will include at a minimum: heart and respiratory auscultation; 
peripheral arterial pulse; pupil, knee, Achilles and plantar reflexes; peripheral lymph 
nodes and abdomen examination. 
Symptom directed physical examination: body systems will be reviewed only if clinically 
indicated and at the discretion of the Principal Investigator or delegate. Symptom directed 
physical examination may be performed as required by the Principal Investigator or 
delegate throughout the study.  
Full physical examination will be performed at Screening and at EOS.  
After inoculation with the malaria challenge agent on Day -8, physical examination will 
also consider the following: 
• Signs of malaria include fever (oral temperature above 38°C), chills/shivering/rigors, 
tachycardia, hypotension 
• Symptoms of malaria include headache, myalgia, arthralgia, fatigue/lethargy, 
malaise, sweating/hot spells, anorexia, nausea, vomiting and abdominal discomfort. 


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Symptom-directed physical examination may be performed at the discretion of the 
Principal Investigator or delegate as outlined below:  
• On Day -8 prior to inoculation with the malaria challenge agent,  
• Once daily on Day -4, Day -3, and Day -2   
• Upon admission to the clinical unit on Day -1 (PM),  
• During confinement at the clinical unit from Day 1 until discharge, symptom-
directed physical examination will be performed when clinically indicated including 
if signs or symptoms of malaria are identified. 
• Prior to the discharge of volunteers from the clinical unit on Day 5 after confinement 
for IMP administration, clinical staff will check with the Principal Investigator or 
delegate to clarify if any volunteer will require a symptom directed physical 
examination.   
• After discharge from the clinical unit on Day 5, symptom-directed physical 
examination will be performed at outpatient monitoring visits if clinically indicated, 
including if signs or symptoms of malaria are identified.   
7.2 
VITAL SIGNS, TEMPERATURE AND BODY MEASUREMENTS 
7.2.1 Body Measurements and Temperature 
Body weight (kg) and height (cm) will be measured at screening. Body weight (kg) will 
also be measured at the eligibility visit between Days -11 to -9 and at EOS.  
Tympanic body temperature (°C) will be taken at screening, on Day -8 prior to inoculation 
with the malaria challenge agent, on Day -4, on Day -3 at least once and twice at the 
discretion of the Principal Investigator or delegate, twice daily on Days -2 and -1, then at 
the following times post-IMP administration during confinement: Day 1 pre-dose, then t 
= 1, 2, 4, 6, 8, 10, 12, 24, 30, 36, 48, 60, 72, 84, 96 and 108  hours post-IMP administration. 
After discharge from the clinical unit, oral body temperature will be taken at every 
subsequent outpatient visit to the clinical unit including EOS.   
NOTE: On Day -8 after inoculation with the malaria challenge agent and prior to leaving 
the clinical unit, each volunteer will be issued a diary and thermometer to record their 
temperature in the event of symptoms of fever. The volunteers will bring their diaries to 
each subsequent visit to the clinical unit.  
Time windows are as described for Vital Signs in Section 7.2.2.   
7.2.2 Vital signs 
• Screening and EOS: heart rate, systolic and diastolic blood pressure will be measured 
after 5 minutes in supine resting position, and after 3 minutes in standing position. 
• For all other timepoints, heart rate, systolic and diastolic blood pressure will be 
measured after 5 minutes in supine resting position.  
Vital signs will be measured at Screening, on Day -8 both prior to and approximately 60 
minutes after inoculation with the malaria challenge agent, on Day -4, on Day -3 (at least 
once, and twice at the discretion of the Principal Investigator or delegate), twice daily on 
Days -2 and -1. From Day 1, vital signs will be measured pre-dose and at the following 
times post-IMP administration: 1, 2, 4, 6, 8, 10, 12, 24, 30, 36, 48, 60, 72, 84, 96 and 108 
hours (prior to discharge from the clinical unit). After discharge from the clinical unit, 
vital signs will be measured at each outpatient visit (at least once per day if visits twice 
daily at the discretion of the Principal Investigator or delegate).  


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Permitted time windows for vital sign measurements during confinement: 
• ± 10 min of PK sampling (see Table 5) 
• ± 1h for timepoints where no PK sample is collected 
For post-confinement visits, time windows are as per  Table 5 when PK samples collected.  
7.3 
12-LEAD ELECTROCARDIOGRAM (ECG) 
Standard 12-lead ECGs (safety ECGs) will be recorded after at least 10 minutes in supine 
position using a validated electrocardiographic device. The electrodes will be positioned 
at the same place for each ECG recording throughout the study (attachment sites of the 
leads will be marked with an indelible pen).  
When triplicate ECGs are required, 3 ECGs will be recorded within 5 minutes with at 
least 1 minute between 2 replicates. Each ECG consists of a 10-second recording of the 
12 leads simultaneously, leading to:  
• A single 12-lead ECG (25 mm/s, 10mm/mV) printout with heart rate, PR, QRS, QT, 
QTc automatic correction evaluation (by the ECG device), including date, time, 
initials, and number of the volunteer, signature of the research physician, and at least 
3 complexes for each lead. The Principal Investigator’s or delegate’s medical opinion 
on clinical significance and automatic values will be recorded in the eCRF. This 
printout will be retained at the site. 
Triplicate ECGs will be conducted at the following timepoints: 
• Screening visit 
• Day -8 pre-inoculation with the malaria challenge agent  
• Day 1 pre-dose 
Single 12-lead safety ECGs will be conducted at the following timepoints: 
• Day -1 morning, Day 1 at the following hours post-IMP administration: 
o 4, 6, 8, 12, 24, 48, 72 and 96 
• Days 8 (±2 days) , 14 (±2 days), 21 (±3 days), pre-dose on day of rescue 
medication, 25 (±3 days) and EOS 
Permitted time windows for 12-lead ECGs during confinement: 
• ± 10 min of PK sampling, preferably before PK sampling (seeTable 5) 
• ± 1h for timepoints where no PK sample is collected 
For post-confinement visits, time windows are as per  Table 5 when PK samples collected. 
7.4 
MALARIA CLINICAL SCORE  
The Malaria Clinical Score will be used to quantify signs and symptoms of malaria in 
volunteers after they have been inoculated with the malaria challenge agent (see Appendix 
2: Malaria Clinical Score).   
The 14 signs/symptoms frequently associated with malaria are graded using a 4-point 
scale (Absent 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria 
clinical score (maximum score possible is 42).  
To determine severity of the 14 signs/symptoms, the Principal Investigator or delegate 
will use the Common Terminology Criteria for Adverse Event Reporting (CTCAE) Grade 


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1 - 5 Version 5.0 Published: November 27, 2017. Mild (1) equates to CTCAE grade 1, 
Moderate (2) equates to CTCAE grade 2 and Severe (3) equates to CTCAE grade 3.  
See Detailed Schedule of Activities Table 2 and Table 3 for the detailed schedule for 
recording the Malaria Clinical Score. The score will be recorded for volunteers prior to 
and approximately 60 minutes after inoculation with the malaria challenge agent on Day 
-8, once on Day -4,  at least once, and twice at the discretion of the Principal Investigator 
or delegate on Day -3, and twice daily on Days -2 and -1. On Day 1, the Malaria Clinical 
Score will be recorded prior to IMP administration, and then at t = 2, 6, 12, 24, 30, 36, 48, 
60, 72, 84, 96 and 108 hours post-IMP administration. After the volunteers are discharged 
from the clinical unit, the Malaria Clinical Score will be recorded at each visit when 
samples for Malaria 18S qPCR are taken, pre-dose on day of rescue medication and at 
EOS.  
In the case of anti-malarial rescue treatment being required before Day 21±3, safety 
assessments including the Malaria Clinical Score must be continued as per the Detailed 
Schedule of Activities Table 2 and Table 3, and must be performed at a minimum 72 hours 
after rescue treatment was completed.   
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. 
7.5 
CLINICAL LABORATORY TESTS 
Blood and urine will be collected for clinical laboratory safety tests conducted at the 
clinical unit’s preferred Vendor laboratory unless otherwise stated. Handling of samples 
is described in the Pathology Vendor Laboratory Manual.  
• For the biochemistry and haematology safety laboratory tests scheduled for 
Screening, safety visit during Days -11 to -9, and on Day -1, volunteers must 
attend the clinical unit having fasted for at least 8 hours. Other scheduled 
timepoints for safety laboratory testing do not require the volunteer to have fasted 
overnight.  
• The Principal Investigator or delegate must review all results and assign clinical 
significance to any out of range results. Results must also be reviewed with 
reference to Section 4.3.8 and Adverse Events of Special Interest (AESIs) as 
defined in Section 7.9.5. 
• Results of safety laboratory tests must be available and reviewed by the Principal 
Investigator or delegate prior to inoculation with the malaria challenge agent and 
IMP administration  (except results of Day 1 pre-dose safety sampling). On 
Day -1, the blood sample for haematology and biochemistry clinical laboratory 
safety tests will be collected approximately 24 hours prior to IMP dosing to check 
for potential safety signals occurring after inoculation with the malaria challenge 
agent. Results must be reviewed by the Investigator prior to confirming IMP 
dosing may proceed.  
7.5.1 Safety Blood Tests 
Blood for safety blood tests will be collected: 
Screening (fasted), once between Day -11 to Day -9 (fasted, with results to be available 
prior to inoculation with the malaria challenge agent on Day -8), Day -3 (LFTs only), Day 
-1 (fasted; NOTE: results must be available for review by the Principal Investigator or 
delegate prior to IMP administration on Day 1 to check for safety signals resulting from 
inoculation with the malaria challenge agent), Day 1 pre-dose and at the following hours 
post-IMP administration: 24, 48, 72 and 96 hours prior to discharge from the clinical unit. 


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After discharge from the clinical unit, blood will be collected on Days 8 (±2 days), 14 (±2 
days), 21 (±2 days) (pre-dose on day of rescue medication), Day 25 (±2 days) and EOS. 
7.5.1.1 Haematology  
Red blood cell count, haematocrit, haemoglobin, white blood cell count with differential 
count (neutrophils, eosinophils, basophils, monocytes, and lymphocytes), platelets. 
7.5.1.2 Biochemistry  
• Plasma/serum electrolytes (sodium, potassium, chloride, calcium, magnesium);  
• Liver function tests (AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, 
glutamate dehydrogenase, total and conjugated bilirubin, biliary acids);  
• Renal function (urea, creatinine)  
• Metabolism (glucose, albumin, total proteins, total cholesterol, triglycerides)  
• Potential muscle toxicity (creatinine phosphokinase)  
• CRP 
• Screening visit only: glucose-6-phosphatase (G6PD)  
7.5.2 Coagulation 
Blood will be collected for coagulation studies only at screening and will include 
international normalized ratio (INR) and activated partial thromboplastin time (APTT).  
7.5.3 Serology 
Blood will be collected for serology tests at screening and EOS and will include: hepatitis 
B surface antigen (HB sAG), anti-hepatitis B core antibodies (anti-HBc Ab), hepatitis C 
antibodies, anti-HIV1 and anti-HIV2 antibodies. Red blood cell alloantibodies will also 
be assayed for all volunteers. 
7.5.4 Pregnancy and Follicle Stimulating Hormone (FSH) Testing 
7.5.4.1 Pregnancy Testing 
Blood will be collected from all female volunteers for serum β-human chorionic 
gonadotropin (β-hCG) testing at screening for the study.  Blood will be collected from 
WOCBP for serum β-hCG testing at EOS for the study.   
Urine will be collected from volunteer WOCBP for β-hCG testing by the clinical unit: for 
visit(s) between Days -9 to -11 prior to inoculation with the malaria challenge agent and 
Day -1 prior to IMP administration.  
Blood will also be collected from a female volunteer for unscheduled serum β-hCG testing 
if their urine β-hCG test returns a positive result. 
7.5.4.2 Confirming Menopause 
Blood will be collected from post-menopausal female volunteers for follicle stimulating 
hormone (FSH) testing at screening only.  
7.5.5 Red Blood Cell alloantibodies 
Blood will be collected from volunteers only at Screening and EOS to test for red blood 
cell alloantibodies. 
7.5.6 Urinalysis 
Urine will be collected as part of the clinical laboratory safety testing at the same 
timepoints as for safety blood tests above in Section 7.5.1 up to and including t = 24 hours 


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post-dose (except Day -3), and then only at t = 72 hours post-dose, Days 8 (±2 days), 14 
(±2 days), 21 (±2 days) (pre-dose on day of rescue medication) and EOS. The urinalysis 
will test for proteins, glucose, erythrocytes, leucocytes, ketone bodies and pH.  
Qualitative: a dipstick test will be performed on a freshly voided urine sample. 
Quantitative: if the urine sample dipstick test is positive for glucose, protein, erythrocytes 
or leucocytes, quantitative measurement of these parameters by pathology laboratory is 
required.  
7.6 
RETENTION SAMPLES 
IMP SAFETY SERUM SAMPLES 
A 5mL blood sample will be collected on Day -8 prior to inoculation with the malaria 
challenge agent and at EOS.  
Volunteers consent to this mandatory collection and storage and the use of the sample for 
safety assessments when they sign the Informed Consent Form for the study. These 
samples will be used if any unexpected safety issue related to the IMP occurs to ensure 
that a pre-administration baseline value is available for parameters not previously 
planned/assessed (eg, serology).  These samples will be stored at Nucleus Network. If the 
sample is not used, the Principal Investigator or delegate will destroy it at the end of the 
study and final CSR is available after Sponsor approval. 
INOCULUM SAFETY SERUM SAMPLES 
A 5mL blood sample will be collected on Day -8 prior to inoculation with the malaria 
challenge agent and at EOS.  
Volunteers consent to this mandatory collection and storage and the use of the sample for 
safety assessments related to the inoculum when they sign the Informed Consent Form 
for the study. Inoculum safety samples will be retained for at least 15 years from the 
completion of the study at the QIMR Berghofer Institute. 
RESEARCH SERUM SAMPLES 
Under a separate protocol and consenting process, research serum samples may be 
collected for storage and use in future malaria research. The separate study will be under 
the local sponsorship of QIMR Berghofer Institute and will involve a protocol and consent 
document approved by the QIMR HREC.  
Only if the volunteer consents to the separate study, up to four (4) blood samples will be 
collected at timepoints that coincide with visits under the MMV533-VIS protocol 
including timepoints prior to and after inoculation (see SOAs Table 1, Table 2 and Table 
3 in Section 1.3).  
Blood volume of each sample may be up to and not exceeding 30 mL:  
• And will be an appropriate volume for the day/timepoint, AND 
• The total volume of blood taken including the main study samples will not exceed 
450 mL per month. 
A volunteer’s decision can be changed at any time prior to the EOS by notifying QIMR, 
as local Sponsor, in writing. However, if a volunteer consents to future use and some of 
their blood has already been used for research purposes, the information from that 
research may still be used. 


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7.7 
ALCOHOL AND DRUG SCREENING 
Alcohol will be measured by breath test at the clinical unit.  
Urine will be collected for drug screening, using suitable dipstick test at the clinical unit 
for: amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, 
methadone, opiates, phencyclidine, tetrahydrocannabinol, tricyclic antidepressants. 
Alcohol and drug screening will be conducted at screening, Day -8 prior to inoculation 
with the malaria challenge agent and Day -1 prior to IMP dosing.  
Unscheduled alcohol and drug screening may be performed if required for volunteer 
safety or to assess continued eligibility at the discretion of the Principal Investigator or 
delegate.  
7.8 
BECK DEPRESSION INVENTORY 
Originally described by Beck et al (1961), the Beck Depression Inventory (BDI) is a 
validated objective tool for the assessment of depression. Updated in 1996, the BDI-II is 
a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms 
of depression, and volunteers will be required to complete the BDI-II at Screening for 
eligibility.12 The BDI-II takes approximately 10 minutes to complete, although clients 
require a fifth – sixth grade reading level to adequately understand the questions. A score 
of >20 at screening and/or a response of 1, 2 or 3 for item 9 indicating current suicidal 
ideation is exclusionary. A BDI-II score of 17 to 19 may be enrolled at the discretion of 
the Principal Investigator if they do not have a history of the psychiatric conditions 
mentioned in exclusion criterion 26 and their mental state is not considered to pose 
additional risk to the health of the volunteer or the execution of the study and 
interpretation of the data gathered. The results will be entered into the eCRF.  
7.9 
ADVERSE EVENTS (AEs) 
The Principal Investigator or delegate and clinical unit staff are responsible for detecting 
recording and reporting events that meet the criteria and definition of adverse events as 
described below. Adverse events may be reported by the volunteer (including in the diary) 
or observed by the Principal Investigator, delegate or other clinical site staff.   
All AEs will be followed until the event has resolved, no further medically relevant 
information from the event can be expected and it is acceptable to discontinue follow-up 
of the event in the assessment of the Principal Investigator. The Principal Investigator 
should continue to follow up AEs that were unresolved at the volunteer’s EOS as long as 
medically required or until the volunteer has been satisfactorily referred to a general 
practitioner or medical specialist as appropriate.  
Medically untoward events occurring in volunteers between the time of consent 
(screening) and the time of inoculation with the malaria challenge agent will be considered 
medical history and not recorded as AEs. 
See Section 6.1.5 for Note on appropriate consideration of COVID-19 symptoms. 
7.9.1 Definitions 
An adverse event (AE) is any untoward medical occurrence in a clinical trial volunteer 
administered a medicinal product, and that does not necessarily have a causal relationship 
with this treatment. In this study, AEs will also be recorded for the period after inoculation 
with the malaria challenge agent and prior to IMP administration.  
AEs include, but are not limited to: 


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• A new symptom, sign or medical condition which develops after inoculation with 
the malaria challenge agent. 
• A disease or medical condition detected or diagnosed during the course of the study 
even though it may have been present prior to the start of the study. 
• An exacerbation of a pre-existing medical condition/disease. 
• An increase in frequency or intensity of a pre-existing episodic disease or medical 
condition. 
• Continuous persistent disease or symptoms present at study start that worsen 
following the start of the study. 
• An abnormal assessment (e.g., change on physical examination, ECG finding) if it 
represents a clinically significant finding that was not present at study start or 
worsened during the course of the study. 
• An abnormal laboratory test result if it represents a clinically significant finding 
(e.g., CTCAE grade 2 or above), symptomatic or not, which was not present at study 
start or worsened during the course of the study or led to dose reduction, interruption 
or permanent discontinuation of study treatment. 
Abnormal laboratory findings and other objective assessments should NOT be routinely 
captured and reported as AEs. However, abnormal laboratory findings or other objective 
measurements that meet the following criteria should be captured and reported in the AE 
Section of the eCRF: 
• The result meets the criteria for reporting as an SAE (Section 7.10.1) or AESI 
(Section 7.9.5); 
• The test result is associated with accompanying symptoms, and/or 
• It requires additional diagnostic testing or medical/surgical intervention, and/or 
• It leads to a change in IMP dosing, or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or 
• It is considered by the Principal Investigator (or delegate) or Sponsor to be clinically 
significant or represent a clinically significant change from baseline. 
AEs will not include: 
• A medical or surgical procedure such as surgery, endoscopy, tooth extraction, or 
transfusion (although the condition that leads to the procedure may be an AE).  
• A pre-existing disease or condition present at the start of the study that does not 
worsen during the study. 
• Any situation where an untoward medical occurrence has not occurred (for example, 
hospitalizations for cosmetic elective surgery or social admissions). 
 
7.9.2 Causal Relationship to Investigational Medicinal Product and Other Study 
Treatments 
The Principal Investigator or delegate is required to assess the causality to study 
interventions for all AEs, and must indicate this in the source document and eCRF (study 
interventions include: inoculation with the malaria challenge agent, IMP administration 
and administration of anti-malarial rescue medication).   
An adverse event with reasonable causal relationship to the IMP means there is evidence 
or argument to suggest a causal relationship.  
If considered related: 


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• The temporal relationship between the event and the administration of the IMP is 
compelling and/or follows a known or suspected response pattern to that product, 
and the event cannot be explained by the volunteer’s medical condition, other 
therapies or accident.  
If considered not related: 
• The event can be readily explained by other factors such as the volunteer’s 
underlying medical condition, concomitant therapy or accident and no plausible 
temporal or biologic relationship exists between the IMP and the event. 
7.9.3 Severity Grading of Adverse Events 
The severity of AEs will be recorded in accordance with the Common Terminology 
Criteria for Adverse Events (CTCAE) v5.0, published 27 November 2017. This guidance 
provides a common language to describe levels of severity, to analyse and interpret data, 
to scale the aggregate AE score, and to articulate the clinical significance of all AEs. 
The severity of AEs will be graded as follows:  
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
• Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting 
self-care activities of daily living. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
An AE that is assessed as severe is not the same as a serious AE. Severity is a category 
utilized for rating the intensity of an event and both AEs and SAEs can be assessed as 
severe. An AE is defined as ‘serious’ when it meets one of the pre-defined serious 
outcomes as described below in Section 7.10.1. 
7.9.4 Documentation of Adverse Events 
The Principal Investigator or delegate is responsible for reviewing all documentation 
related to each AE (including volunteer diaries), and for recording all relevant AE/SAE 
information in source document and in the eCRF. The Principal Investigator or delegate 
will attempt to establish a diagnosis of the AE based on signs, symptoms and/or other 
clinical information, and where possible the diagnosis will be documented as the AE/SAE 
(and not individual signs or symptoms). Clinically significant abnormal safety assessment 
findings should be documented as AEs unless regarded as signs or symptoms of an AE.   
The following information should be recorded for all AEs: 
• Description 
• Dates and times of onset and resolution 
• Time of onset relative to IMP administration, inoculation with the malaria 
challenge agent, and/or administration of antimalarial rescue medications 
• Seriousness  
• Severity 
o In the source data, the description of the AE will report the various 
severities observed over time. If the severity of an AE increases, separate 


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AEs per severity grading will be recorded into the eCRF.If the AE resolves 
and then reoccurs, then two AEs will be reported. 
• Action taken in response to the AE regarding IMP: 
o No action taken, or 
o Rescue medication administered instead of IMP, or 
o Not applicable.  
• Outcome of AE: 
o Recovered/resolved, or 
o Recovering/resolving, or 
o Not recovered/not resolved, or 
o Recovered with sequelae/resolved with sequelae 
o Fatal 
o Unknown  
• Relationship to the IMP or procedures conducted during the trial including 
inoculation with the malaria challenge agent or treatment with rescue medication 
(causality assessment).  
7.9.5 Adverse Events of Special Interest (AESI) 
Adverse Events of Special Interest (AESIs) may be serious or non-serious, and are defined 
by the Sponsor as being of specific scientific and/or medical concern to the Sponsor’s 
product or programme. AESIs will be required to be monitored and reported promptly to 
the Sponsor by the Principal Investigator or delegate. Such an event may require further 
investigation in order to characterise and understand it. 
All AESIs (both serious and non-serious) must be notified to the pharmacovigilance 
provider (Prime Vigilance) within 24 hours of the clinical study staff becoming aware of 
the event (see Section 7.10.3 below). Reporting should be via a Serious Adverse Event 
Report Form marked as ‘AE of special interest’. Follow-up information will be submitted 
in a timely fashion as it becomes available.  
7.9.5.1 Hepatic AEs of Special Interest 
• Any ALT or AST above 5×ULN, 
• An elevation in bilirubin 2×ULN, 
• Any AST or ALT above 2×ULN and Total Bilirubin Level (TBL) >1.5×ULN or 
INR >1.4, 
• Any AST or ALT above 2×ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (eosinophil 
percent or count above the ULN). 
7.9.5.2 Cardiac AEs of Special Interest 
• QTcB or QTcF at any time >480 msec, 
• Bundle branch block (except right bundle branch block that was present prior to 
IMP administration), 
• Any arrhythmia, except: 
o Sinus bradycardia that is clinically asymptomatic, and not associated with 
any other relevant ECG abnormalities, 
o sinus tachycardia that is clinically asymptomatic, and associated with a 
body temperature >38.0°C, and not associated with any other relevant 
ECG abnormalities, 
o Respiratory sinus arrhythmia, 
o Wandering atrial pacemaker, 


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o Isolated, single premature atrial/ventricular complex (i.e., no bigeminy, 
trigeminy, couplets, triplets or salvos) that does not occur more than once 
in a particular ECG tracing. 
7.9.5.3 Haematological AEs of Special Interest 
• Haemoglobin drop >20.0 g/L from baseline prior to inoculation, 
• Absolute neutrophil count <0.5 × 109/L, 
• Platelet count <75 × 109/L. 
7.9.5.4 Dermatological AEs of Special Interest 
Clinical signs of possible cutaneous adverse reactions such as:  
• Dermatitis, 
• Rash, including erythematous, macular, papular, maculopapular, pruritic, 
pustular, and vesicular. 
If one of these cutaneous reactions are observed and when feasible, pictures of the lesions 
should be obtained. 
Dermatological AEs do not need to be reported as AESIs if clearly unrelated to inoculum 
or study drug (e.g. rash from cannula dressing or ECG dots). 
7.9.6 Treatment of Overdose 
Overdose of IMP is considered unlikely as it is a single dose administered under 
supervision at the clinical unit. However symptomatic overdose of IMP or of other study 
treatments/interventions (ie, malaria challenge agent, malaria rescue medications) is an 
event suspected by the Principal Investigator or delegate, or notified by the volunteer, and 
defined as at least twice the intended dose within the intended therapeutic interval adjusted 
according to the tested drug. Such an event should be reported promptly to the Sponsor 
as for AESIs.  Asymptomatic overdose will be reported as a standard AE.   
7.10 SERIOUS ADVERSE EVENTS (SAES) 
7.10.1 Definitions of Serious Adverse Events (SAEs) 
A serious adverse event (SAE) is any AE that: 
• Results in death, or 
• Is life-threatening, and/or 
• Requires inpatient hospitalisation or prolongs existing hospitalisation, and/or 
• Results in persistent or significant disability or incapacity, and/or 
• Is a congenital anomaly or birth defect, and/or  
• Constitutes a possible Hy’s Law case: 
o Hy’s Law case is defined as a volunteer with any value of alanine or 
aspartate aminotransferase greater than 3×ULN together with an increase 
in total bilirubin to a value greater than 2×ULN and not associated to an 
alkaline phosphatase value greater than 2×ULN (FDA Guidance on Drug 
Induced Liver Injury: Premarketing Clinical Evaluation [2009]). 
Note: Life-threatening in the definition of an SAE refers to an event in which the 
volunteer was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe. 
Note: Medical and scientific judgement should be exercised in deciding whether an AE 
should be classified as serious in other situations. Important medical events that are not 
immediately life-threatening or do not result in death or hospitalization, but may 


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jeopardise the volunteer or may require intervention to prevent one of the other outcomes 
above should also be considered serious.  
Planned procedures that require admission to hospital for this study, or any planned 
elective procedure that requires hospitalization are not considered SAEs unless the 
underlying condition has worsened or the volunteer’s condition worsens after the 
procedure.  
7.10.2 Pregnancy 
Pregnancy itself is not defined as an AE/SAE. Any complication or termination of 
pregnancy for medical reasons are to be reported as an AE/SAE. Spontaneous abortion, 
still birth or congenital anomaly must be reported as an SAE.  
Any WOCBP (Woman of Child-Bearing Potential) enrolled in the study who becomes 
pregnant during the study and the following 60 days after the dosing should be followed 
through delivery or termination of the pregnancy. The Investigator will collect pregnancy 
information and report to the Sponsor within 24 hours of becoming aware of a volunteer’s 
pregnancy. Follow-up will generally not be required for longer than 6 to 8 weeks beyond 
the estimated delivery date. Once pregnancy is confirmed, pregnant female volunteers 
will be immediately withdrawn from the study as outlined in Section 4.3.5.   
Where possible, the Investigator will also attempt to collect and report information 
regarding pregnancy outcomes of female partners of any male volunteers who were 
administered IMP in this study and the following 60 days after the last dosing. Appropriate 
signed informed consent will be required directly from the pregnant female partner to 
obtain and report this information.  Any volunteer’s female partner who becomes pregnant 
during the study should be followed through delivery or termination of the pregnancy. 
7.10.3 Reporting for Serious Adverse Events (24 hours) 
If any SAE occurs, the Investigator will take immediate appropriate action and strive to 
identify the causes of the event/s. The Investigator must notify the SAE to the 
pharmacovigilance provider (Prime Vigilance) by email within 24 hours of becoming 
aware of the event. Safety reporting for the study will be further outlined in the study-
specific Safety Plan.  
All reports must be signed by the Principal Investigator or delegate and notified to Prime 
Vigilance preferably by email or fax to: 
Email: MMV@primevigilance.com 
Back-up fax number: +44 800 471 5694 
Prime Vigilance Contact:  
Andreja Baricevic 
e-mail: andreja.baricevic@primevigilance.com 
Phone: +44 385 1 46 28 183 
Mobile: +44 385 99 2680 787 
Head Office: +44 1483 307920 
Any copies of volunteer’s medical records provided for SAE reporting must have all 
volunteer identifiers redacted before submission.   
The SAE report form will always be completed as thoroughly as possible with all 
available details of the event and signed by the Principal Investigator or delegate. If the 
Principal Investigator or delegate does not have all information regarding an SAE, he/she 


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will not wait to receive additional information before reporting the event. A follow-up 
SAE report should be completed within 14 days, or if there is no new information the 
SAE report form should be updated when additional information is received. 
The Principal Investigator or delegate will always provide an assessment of causality at 
the time of the initial report. 
Email transmission of the SAE report form is the preferred method to transmit this 
information to Prime Vigilance. In rare circumstances notification by telephone is 
acceptable, with a copy of the SAE report form sent by overnight mail.  
The Principal Investigator or delegate, or responsible person according to local 
requirements, will comply with the applicable local regulatory requirements related to the 
reporting of SAEs to regulatory authorities and the HREC.  
7.11 SAFETY REVIEW COMMITTEE (SRC) 
The SRC will be responsible for decisions related to the safety of volunteers and to inform 
decision making on trial progression and details will be outlined in the Safety Plan. The 
required data to be reviewed will be detailed in a separate trial-specific Safety Review 
Committee Charter and will be sent to the SRC prior to all scheduled and any ad hoc SRC 
meetings associated with the trial.  
The Safety Review Committee (SRC) will be composed at a minimum of the Sponsor’s 
Medical Director, the Principal Investigator, the study Medical Monitor and the Malaria 
Physician. Representative/s for PK analysis will also be included. The study will proceed 
cohort by cohort with SRC review in between each cohort. The SRC may decide to 
discontinue the study after any of the cohort reviews.  
The SRC will choose the dose levels for cohorts 2 and 3 based upon their review of the 
appropriate data from cohort 1. For each of the cohorts, the SRC will review safety and 
tolerability data up to Day 22 and PK and PD analysis of data up to day 15 before the next 
cohort is given permission to proceed with inoculation with the malaria challenge agent 
on Day -8.  
8 STATISTICAL ANALYSES 
8.1 
GENERAL APPROACH 
The following sections describe the statistical analysis as it is foreseen during the planning 
phase of trial. A detailed Statistical Analysis Plan (SAP) will be finalised and approved 
prior to database lock and will provide details of all analyses to be performed as well as 
the format of listings and tables to be provided for completion of the clinical study report 
(CSR). Any deviations from the SAP will be described and justified in the final CSR.  The 
PK and PD analyses may be detailed in a separate analysis plan, as deemed appropriate. 
 
The general analytical approach for all safety endpoints will be descriptive in nature. 
Unless otherwise stated, the following statistical approaches will be taken: 
Continuous variables:   
Descriptive statistics will include the number of non-
missing values, mean, standard deviation (SD), median, 
minimum, and maximum.  The minimum and maximum 
values will be presented to the same number of decimal 


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places as recorded in the CRF; mean, median and SD will 
be presented to one more decimal place than the raw data. 
Categorical variables:   
Descriptive statistics will include frequency counts and 
percentages per category. Percentages will be rounded to 
one decimal place, with the denominator being the number 
of volunteers in the relevant population with non-missing 
data. 
Imputation:   
No missing data will be imputed. 
Confidence intervals (CIs):  If required, CIs will be two sided and will use 95% 
confidence levels. Any analyses requiring significance 
testing will use a two-sided test at the 5% significance level. 
 
Baseline:   
The inoculation baseline will be defined as the last available 
assessment prior to the inoculation.  
 
Unscheduled assessments: 
Unscheduled visits will be excluded from summary tables. 
 
Early termination visits: 
Assessments conducted at Early Termination will be 
excluded from summary tables. 
 
8.2 
SAMPLE SIZE AND JUSTIFICATION 
Up to 24 volunteers (8 volunteers per cohort, all receiving MMV533). The sample size of 
the study is based on experience from previous Phase 1 IBSM trials. 
 
8.3 
ANALYSIS SETS AND SUB-SETS 
8.3.1 Analysis Sets 
In the first instance, two (2) analysis datasets will be used for study analyses: Full Analysis 
Set (FAS) and Safety Set.   
Additional analysis populations may be defined in the SAP or the PK Analysis Plan. 
The number of volunteers in each analysis set will be summarised, with a corresponding 
listing. 
8.3.1.1 Full Analysis Set 
The Full Analysis Set (FAS) will consist of all enrolled volunteers.  The FAS will be used 
to assess all volunteer disposition, baseline, demographic and protocol deviation data. 
8.3.1.2 Safety Set 
The Safety Set will include all enrolled volunteers who received at least one dose (full or 
partial) of IMP. 
8.4 
VOLUNTEER DISPOSITION 
A listing of volunteer disposition will present volunteer dates of informed consent, 
enrolment, randomisation, key visits as well as study completion details. Early 
termination data, including the reason for early termination will be listed in an additional 
listing.  


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A volunteer disposition summary table will present, at a minimum, the number of 
volunteers who completed the study per protocol and the number of volunteers who 
discontinued classified by reason for early termination.   
8.5 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
8.5.1 Demographics 
Demographic data will be listed for all enrolled volunteers and summarised by treatment 
arm and overall.  
8.5.2 Medical History 
All medical history data will be listed, grouped by volunteer. 
Medical history will be coded using the Medical Dictionary for Regulatory Activities and 
summarised by system organ class (SOC) and preferred term (PT). 
8.5.3 Prior Medications 
Prior medications will be listed for all enrolled volunteers. Prior medications are defined 
as any medication that is started before first inoculation with the malaria challenge agent, 
regardless of when it ended. If a medication has a missing or partial missing start/end date 
or time and it cannot be determined whether it was taken before IMP or concomitantly, it 
will be considered as prior and concomitant. 
8.5.4 Eligibility 
Eligibility will be listed for all enrolled volunteers. 
8.6 
PROTOCOL DEVIATIONS 
All protocol deviations will be listed. A protocol deviation summary table will present the 
total number of protocol deviations as well as the number of volunteers who reported at 
least one protocol deviation, broken down by deviation type. 
8.7 
TREATMENT EXPOSURE 
Volunteer exposure to all protocol-specified treatments will be listed and summarised.   
8.8 
SAFETY (PRIMARY ENDPOINT) 
8.8.1 Safety Endpoints 
Safety and tolerability will be assessed by clinical review of the following parameters:  
• AEs (including SAEs and AESIs) 
• Vital signs  
• 12-lead ECG 
• Haematology, chemistry, urinalysis 
• Physical examination 
 
All descriptive statistics for safety parameters will be evaluated using the Safety Set. 
8.8.2 Adverse Events 
All AE data will be listed for each volunteer, including severity, relationship to IMP, 
relationship to non-IMP protocol-specific treatments, outcome and actions taken. In 
addition, listings of AEs leading to discontinuation of the study, SAEs and deaths, will be 
provided as applicable.  


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All AE summaries will be restricted to Treatment Emergent Adverse Events (TEAEs) 
only, where a TEAE is defined as an AE that commences on, or after, the first 
administration of IMP up to the end-of-study (EOS) visit (inclusive). TEAEs without an 
onset date or time will be defined as treatment emergent except if an incomplete date (e.g., 
month and year) clearly indicates that the event started prior to first administration of 
IMP, or if the AE stop date indicates that the event started and/or stopped prior to the first 
administration of IMP.  
The safety analysis will also be done specifically for the inoculation period, defined as 
the time from the inoculum injection (Day-8) to the day before the IMP administration 
(Day-1) visit (included). 
Adverse events (AE) will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA) and grouped by system organ class (SOC) and preferred terms (PT).  
Their severity will be graded according NCI-CTCAE v5. 
At a minimum, the following AE summary tables will be provided: 
• Overall summary of TEAEs 
• All TEAEs 
• TEAEs by severity 
• TEAEs by relationship 
• Serious TEAEs  
• TEAEs leading to study withdrawal  
 
8.8.3 Concomitant Medications 
Medications used in this study will be coded using WHODrug Global. 
Concomitant medications are defined as medications continued or newly received at or 
after administration of IMP, through to the End of Study visit. 
If a medication has a missing or partial missing start/end date or time and it cannot be 
determined whether it was taken before initial treatment or concomitantly, it will be 
considered as prior and concomitant. 
Concomitant medications will be summarised by Anatomical Therapeutic Class (ATC) 
and preferred name (PN). The summary tables will show the number and percentage of 
volunteers taking each medication by ATC and PN. 
For the summaries of prior and concomitant medications, volunteers who take the same 
medication (in terms of the ATC and PN) more than once will only be counted once for 
that medication. 
8.8.4 Laboratory Findings 
Laboratory parameters will be listed by volunteer and visit, including: 
• haematology, 
• biochemistry, 
• coagulation, 
• urinalysis, 
• serology, 
• red blood cell antibodies 
• G6PD status (screening only) 
• drug screening, 


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• alcohol screening 
• FSH, and 
• pregnancy test. 
Haematology, biochemistry and continuous urinalysis laboratory data will be summarised 
for each scheduled visit, including observed values, absolute change from each baseline. 
Categorical urinalysis results will be summarised for each scheduled visit using frequency 
tabulations. 
Any available microscopic urinalysis will be listed. 
8.8.5 Physical Examination 
Physical examination parameters will be listed for all volunteers and visits. 
8.8.6 Body Measurements and Body Temperature 
Height and weight will be listed for all volunteers and visits.   
Observed values (including changes from each baseline) will be summarised for weight. 
Body temperature will be listed for all volunteers and visits.  
Observed values, as well as absolute changes from each baseline, will be summarised 
descriptively for all vital sign parameters by visit. 
8.8.7 Vital Signs 
Vital sign parameters will be listed for all volunteers and visits.  
Observed values, as well as absolute changes from each baseline, will be summarised 
descriptively for all vital sign parameters by visit.  
8.8.8 12-lead ECG 
ECG parameters will be listed for all volunteers and visits. Triplicate ECGs will be 
presented in listings for individual readings as well as the mean for each triplicate.  The 
triplicate means will be used for the summary table. 
Observed values, as well as absolute changes from each baseline, will be summarised 
descriptively for all ECG parameters by visit.  A categorical analysis of QTcF and/or 
QTcB changes from each baseline may also be presented. 
8.9 
PHARMACOKINETIC ENDPOINTS 
8.9.1 Pharmacokinetic Parameters 
MMV533 PK profiles will be plotted individually and summarized by dose group. 
MMV533 PK parameters will be calculated using non-compartimental methods from 
plasma concentration-time data and will be summarized by dose group using descriptive 
statistics. 
8.9.2 Pharmacokinetics/pharmacodynamics 
A population PKPD model will be derived from the plasma concentrations of MMV533 
and asexual parasitemia levels deduced from the total parasitemia measured by qPCR 18s 
and female gametocytemia measured by RT-PCR pfs25 in the challenge volunteers. It is 
achieved by sequentially developing a population PK model to describe the observed 
individual PK profiles and a population PD model for quantifying the relationship of 
plasma concentrations and the parasite killing/clearance. The effect MMV533 
concentration on parasite killing/clearance will be described with an Emax model. 


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Alternative models may be tested if the exploration of the data indicate a different 
behavior, e.g. if a lag time is observed before the parasites are cleared. In such case, the 
models tested will be assessed by goodness-of-fit plots and BIC values to retain the best 
model. The estimated population PKPD parameters and between-subject variability as 
well as their relative standard errors will be provided. Other key parameters will be 
derived from the PKPD model including the minimum inhibitory concentration (MIC), 
the minimal parasiticidal concentration (MPC90), and the parasite reduction rate in 48 h 
(PRR48). 
8.10 PHARMACODYNAMIC ENDPOINTS 
Individual total parasitemia (measured by qPCR 18s) and female gametocytemia 
(measured by RT-PCR pfs25) profiles will be plotted. The individual asexual parasitemia 
profiles will be calculated as follows: if the gametocytemia level is lower than 10% of the 
total parasitemia level, the asexual parasitemia level is assumed to be equal to the total 
parasitemia level; otherwise, the asexual parasitemia is considered unknown.  The asexual 
parasitemia profiles will be plotted individually and summarized by doses (median +/- 
95% CI). 
The pharmacodynamic parameters (PRR, Pt1/2, lag phase) calculated as described in 
Marquart et al13 will be summarized using descriptive statistics (n, mean, geometric mean, 
standard deviation, median, Q1, Q3, minimum, and maximum) by dose group. The 
number and percentage of volunteers with absence of asexual parasitemia, the number 
and percentage of volunteers with recrudescence and the time to recrudescence will be 
summarized by dose group.  
8.11 EXPLORATORY PARAMETERS 
If applicable, exploratory parameters will be summarized by treatment group using 
descriptive statistics and may be reported separately. 
8.12 INTERIM ANALYSIS 
This trial has no formal interim analysis. 
9 STUDY ADMINISTRATION 
9.1 
ETHICAL CONSIDERATIONS 
9.1.1 Ethical Principles 
This clinical study was designed and shall be implemented and reported in accordance 
with the Declaration of Helsinki, the Integrated Addendum to ICH E6(R1): Guideline for 
Good Clinical Practice E6(R2) dated 09 November 2016 and the National Statement on 
Ethical Conduct in Human Research, (2007 – updated 2018). 
9.1.2 Informed Consent 
Eligible volunteers may only be included in the study after providing written (witnessed, 
where required by law or regulation), IRB/IEC/HREC-approved informed consent. 
Informed consent must be obtained before conducting any study-specific procedures (i.e. 
all of the procedures described in the protocol). The process of obtaining informed consent 
should be as per local regulatory requirements and documented in the volunteer source 
documents.  A copy of the signed patient information and consent form will be provided 
to the volunteer. 


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9.1.3 Investigator 
and 
Human 
Research 
Ethics 
Committee 
(HREC) 
Responsibilities 
Before initiating a trial, the investigator/institution should obtain approval/favorable 
opinion from the Human Research Ethics Committee (HREC) for the trial protocol, 
written informed consent form, consent form updates, volunteer recruitment procedures 
(e.g., advertisements) and any other written information to be provided to volunteers.  
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 the Sponsor appointed monitors, auditors, Quality Assurance 
representatives, HREC representatives, and regulatory authorities as required. If an 
inspection of the clinical site is requested by a regulatory authority, the investigator must 
inform the Sponsor immediately that this request has been made. 
9.2 
PROTOCOL ADHERENCE 
This protocol defines the study objectives, the study procedures and the data to be 
collected on study volunteers. Additional assessments required to ensure safety of 
volunteers should be administered as deemed necessary on a case by case basis. In this 
instance the Sponsor medical monitor must be advised before or as soon as possible after 
such assessments are conducted.   
Under no circumstances should an investigator collect additional data or conduct any 
additional procedures for any research related purpose involving any investigational 
drugs. Investigators ascertain they 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 the Sponsor and approved by the HREC it cannot be implemented. All protocol 
deviations will be recorded and then reported in the clinical study report (CSR), including 
but not limited to the following deviation categories: 
• Informed consent 
• Eligibility 
• Visit not done 
• Visit performed out of window 
• Study procedure not done 
• Study procedure done out of window 
• Safety reporting 
• Investigational Product 
• Privacy and Data Protection 
• Concomitant Medication 
• Other (including disruptions to the trial due to COVID 19 that are not per protocol) 
9.3 
PROTOCOL AMENDMENTS 
Any change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by the Sponsor and the HREC prior to implementation. Only 
amendments that are intended to eliminate an apparent immediate hazard to volunteers 
may be implemented immediately provided the Sponsors medical monitor is notified as 
soon as possible after the event and the reviewing HREC is subsequently notified. 


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Notwithstanding the need for approval of formal protocol amendments, the investigator 
is expected to take any immediate action required for the safety of any volunteer included 
in this study, even if this action represents a deviation from the protocol. In such cases, 
the Medical Monitor and Sponsor must be notified immediately. 
9.4 
DATA HANDLING AND RECORD KEEPING 
Volunteers will be assigned a unique identifier when participating in the study, and any 
volunteer datasets or records that are transferred to the Sponsor or CRO will only contain 
this identifier. Any other identifiable information about the volunteer will not be 
transferred.  The Principal Investigator will ensure procedures are in place to appropriately 
protect the confidentiality of the volunteer records and data, including adequate safe 
guards for digital/computer access. The volunteers will be informed that their personal 
study-related data will be used by the Sponsor and that their medical records may be 
examined by auditors and regulatory agencies.   
Study-related volunteer data will be entered into electronic case report forms (CRFs) by 
personnel authorized by the Principal Investigator, except for data that may be transmitted 
to the Sponsor or CRO electronically (such as laboratory data). The Principal Investigator 
is responsible for ensuring that accurate source documents for all data entered into the 
CRF are maintained at the study site and that the eCRF is completed accurately. 
Guidelines for eCRF completion including correcting data and responding to data queries 
will be provided by the Sponsor or CRO.  
All study documents including source documents and signed PICFs must be retained by 
the Principal Investigator for at least 15 years and according to local regulatory 
requirements. No study documents may be destroyed or transferred during the retention 
period without the Sponsor being directly notified in writing.  
9.5 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor or CRO maintains responsibility for quality assurance of the data and for 
data management, and retains accountability for actions delegated to other parties 
(including CRO). Study monitors appointed by the Sponsor or CRO will conduct ongoing 
visits to the study sites to confirm the CRF data is accurate according to source documents 
and complete, and that the study is being appropriately conducted according to the 
protocol, ICH GCP and local regulatory requirements. Monitoring visits may be 
conducted remotely if required due to Corona virus disease 2019 (COVID 19) safety 
reasons. 
9.6 
PUBLICATION POLICY 
Neither the complete nor partial results of the study achieved under this protocol, nor any 
of the information provided by the Sponsor for the purposes of performing the study, will 
be published or passed on to any third party without the consent of the study 
Sponsor.  Any Investigator involved with this study is obligated to provide the Sponsor 
with complete study results and all data derived from the study. 
Results of this trial will be either submitted for publication and/or posted in a publicly 
accessible database of clinical trial results.   
 
 


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Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 91 of 96 
 
 
10 REFERENCES 
 
1 World Health Organisation (WHO) (2019). World Malaria Report 2019. Geneva. 
Licence: CC BY-NC-SA 3.0 IGO.  
2 Malaria – Biology (14 November 2018). CDC Centers for Disease Control and 
Prevention, 
USA, 
accessed 
11 
December 
2019,    
https://www.cdc.gov/malaria/about/biology/index.html 
3 McCarthy JS, Sekuloski S, Griffin PM, Elliott S, Douglas N & Peatey C (2011). A Pilot 
Randomised Trial of Induced Blood-Stage Plasmodium falciparum Infections in 
Healthy Volunteers for Testing Efficacy of New Antimalarial Drugs. Public Library of 
Science (PLOS) One 6(8) e21914.  
4 Chughlay MF, Akakpo S, Odedra A, Csermak-Renner K, Djeriou E, Winnips C, 
Leboulleux D, Gaur A, Shanks D, McCarthy J and Chalon S (2020). Liver enzyme 
elevations in P. falciparum CHMI models: findings and recommendations. American 
Journal of  Tropical Medicine and Hygiene;doi: 10.4269/ajtmh.19-0846. Online ahead 
of print. 
5 Griffin, P., et al. (2016) Safety and reproducibility of a clinical trial system using induced 
blood stage Plasmodium vivax infection  and its potential as a model to evaluate malaria 
transmission. PLoS Negl Trop Dis. 10(12): p. e0005139.  
6 Khoury, DS et al. (2016). Defining the effectiveness of antimalarial chemotherapy: 
investigation of the lag in parasite clearance following drug administration. J. Infect. 
Dis. 214(5):753-61. 
7 Engwerda, CR et al (2012). Experimentally induced blood stage malaria infection as a 
tool for clinical research. Trends Parasitol. 28(11):515-21.  
8 Marquart L, Baker M, O’Rourke P & McCarthy J (2015). Evaluating the 
pharmacodynamic effect of antimalarial drugs in clinical trials by quantitative PCR. 
Antimicrobial Agents and Chemotherapy. 59(7):4249-4259. 
9 McCarthy JS, Baker M, O’Rourke P, Marquar TL, Griffin , Hooft van Huijsdiujnen R 
and Mohrle JJ (2016). Efficacy of OZ439 (artefenomel) against early Plasmodium 
falciparum blood-stage malaria infection in healthy volunteers. J. Antimicrob. 
Chemother. 71:2620-2627. 
10 McCarthy JS, Ruckle T, Djeriou E, Cantalloube C, Ter-Minassian D, Baker M, 
O’Rourke P, Griffin P, Marquart L, Hooft van Huijsdiujnen R & Mohrle JJ (2016). A 
Phase II pilot trial to evaluate safety and efficacy of ferroquine against early 
Plasmodium falciparum in an induced blood-stage malaria infection study. Malaria 
Journal 15:469.  
11 Queensland Health (December 2010) Artesunate Powder and diluent for reconstitution 
60mg. Guidance for individual patient approval. Guide for Individual Patient Approval 
(IPA) - Artesunate (health.qld.gov.au) (accessed 16 February 2021) 
 


Medicines for Malaria Venture 
 
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Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 92 of 96 
 
 
12 Beck AT, Ward CH, Mendelson M, Mock J & Erbaugh J (1961). An inventory of 
measuring depression. Archives of General Psychiatry. 4(6):561-671. 
 
 


Medicines for Malaria Venture 
 
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Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 93 of 96 
 
11 APPENDICES 
APPENDIX 
1: 
SPONSOR 
APPROVED 
CLINICALLY 
ACCEPTABLE 
INCLUSION LABORATORY RANGES  
Test 
Unit 
Acceptable Inclusion Range 
Low 
High 
Sodium 
mmol/L 
130 
150 
Potassium 
mmol/L 
3.0 
5.5 
Chloride 
mmol/L 
0.90 x LLN 
1.10 x ULN   
Calcium (Corrected) 
mg/dL 
0.90 x LLN  
1.10 x ULN  
Phosphate 
mmol/l 
0.90 x LLN  
1.10 x ULN  
Bicarbonate 
mmol/l 
0.90 x LLN 
1.10 x ULN 
Glucose Fasted 
mg/dL 
N/A 
1.0 x ULN  
Urea 
mg/dL 
N/A 
1.75 x ULN 
Uric acid 
mg/dL 
N/A 
1.75 x ULN 
Creatinine 
mg/dL 
N/A 
1.0 x ULN  
Creatine kinase 
U/L 
N/A 
< 2.5 x ULN 
eGFR 
mL/min/1.73m2 
60  
N/A 
Total Protein 
g/L 
≥ 0.85 x LLN  
≤ 1.25 x ULN  
Albumin 
g/L 
≥ 0.85 x LLN 
≤ 1.25 x ULN 
Total Bilirubin 
mg/dL 
N/A 
1.25 x ULN 
Direct Bilirubin 
mg/dL 
N/A 
1.25x ULN 
ALP 
U/L 
N/A  
1.5 x ULN 
AST 
U/L 
N/A 
1 x ULN 
ALT 
U/L 
N/A 
1 x ULN 
GGT 
U/L 
N/A 
1.5 x ULN 
Lactate Dehydrogenase 
U/L 
0.9x LLN 
1.1 x ULN 
Prothrombin time INR 
INR 
1.0 x LLN  
1.0 x ULN  
Cholesterol 
mg/dL 
N/A 
1.2 x ULN  


Medicines for Malaria Venture 
 
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Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
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Test 
Unit 
Acceptable Inclusion Range 
Low 
High 
HDL Cholesterol 
mg/dL 
0.9x LLN  
N/A 
LDL Cholesterol 
mg/dL 
N/A 
1.25 x ULN  
Haemoglobin 
g/dL 
0.9x LLN  
1.1.x ULN 
Platelets  
10E9/L 
0.9x LLN  
1.1 x ULN  
White Blood Cells 
10E9/L 
0.9x LLN  
1.1 x ULN  
Neutrophils  
10E9/L 
1.0 x LLN  
1.0x ULN  
Lymphocytes 
10E9/L 
1.0 x LLN  
1.0 x ULN  
Monocytes 
10E9/L 
N/A 
1.2 x ULN  
Eosinophils 
10E9/L 
N/A 
1.0 x ULN  
Basophils 
10E9/L 
N/A 
2.0 x ULN  
C-reactive protein (CRP) 
mg/L 
N/A 
1.0 x ULN 
Troponin-T 
(high 
sensitivity) 
ng/L 
N/A 
< 12 
Protein (dipstick) 
 
N/A 
1+ or 30mg/dL 
Ketones (dipstick) 
 
N/A 
<3+ or <80mg/dL 
Red Blood Cells (MCS) 
 
N/A 
<20* 
White Blood Cells (MCS)  
N/A 
<10 
Casts (MCS) 
 
N/A 
<2/high power field 
*A result ≥ 20 is acceptable for female volunteers currently menstruating. 
 
 
 
 
 
 
 
 
 
 


Medicines for Malaria Venture 
 
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Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 95 of 96 
 
APPENDIX 2: MALARIA CLINICAL SCORE 
Symptoms 
Clinical Score/CTCAE grade  
 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
 
 
CTCAE 1 
CTCAE 2 
CTCAE 3 
Headache 
 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Severe pain; limiting 
self-care ADL 
Myalgia  
 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Severe pain; limiting 
self-care ADL 
Arthralgia  
 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Severe pain; limiting 
self-care ADL 
Fatigue 
 
Fatigue relieved by 
rest 
Fatigue not relieved by 
rest; limiting 
instrumental ADL  
Fatigue not relieved 
by rest; limiting self-
care ADL 
Malaise 
 
Uneasiness or lack 
of well-being 
Uneasiness or lack of 
well-being; limiting 
instrumental ADL 
Uneasiness or lack of 
well-being limiting 
self-care ADL 
Chills 
 
Mild sensation of 
cold; shivering; 
chattering of teeth 
Moderate tremor of the 
entire body; narcotics 
indicated 
Severe or prolonged, 
not responsive to 
narcotics 
Sweating/hot 
spells 
 
Mild sweating/hot 
spells not affecting 
ADL 
Moderate sweating/hot 
spells; narcotics 
indicated 
Severe or prolonged, 
not responsive to 
narcotics 
Reduced 
appetite 
 
Loss of appetite 
without alteration 
in eating habits 
Oral intake altered 
without significant 
weight loss or 
malnutrition; oral 
nutritional supplements 
indicated 
Associated with 
significant weight loss 
or malnutrition (e.g. 
inadequate oral caloric 
and/or fluid intake); 
tube feeding or TPN 
indicated 
Nausea 
 
Loss of appetite 
without alteration 
in eating habits  
Oral intake decreased 
without significant 
weight loss, 
dehydration or 
malnutrition 
Inadequate oral caloric 
or fluid intake; tube 
feeding, TPN, or 
hospitalisation 
indicated 
Vomiting 
 
Intervention not 
indicated 
Outpatient IV 
hydration; medical 
intervention indicated 
Tube feeding, TPN, or 
hospitalisation 
indicated 
Abdominal 
discomfort 
 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Severe pain; limiting 
self-care ADL 
Fever 
 
38.0-38.9°C  
≥39.0-39.9°C  
≥40.0°C  
Tachycardia 
 
HR ≥100 
Asymptomatic, 
intervention not 
indicated 
HR ≥100 Symptomatic; 
non-urgent medical 
intervention indicated 
HR ≥100  Urgent 
medical intervention 
indicated 
Hypotension 
 
SBP ≤80 
Asymptomatic, 
intervention not 
indicated 
SBP ≤80 Symptomatic; 
non-urgent medical 
intervention indicated 
SBP ≤80  Urgent 
medical intervention 
indicated 
Total Score 
 
 
 
 
Maximum  
3 x 14 = 42 
 
Indications for malaria treatment: 


Medicines for Malaria Venture 
 
Version 1.0  
Protocol No: MMV_MMV533_20_01 
 
Date: 01 March 2021 
CONFIDENTIAL  
 
Page 96 of 96 
 
Symptoms 
Clinical Score/CTCAE grade  
• 
Volunteer has a clinical score ≥6, or  
• 
Volunteer has ≥1 CTCAE grade 3 (severe) AE deemed possibly related to malaria and not self-
resolved or relived with concomitant medications, or 
• 
Volunteer experiences ≥1 SAE, or 
• 
The Principal Investigator or delegate considers it necessary for volunteer safety. In this 
situation, the Principal Investigator or delegate will notify the medical monitor prior to initiating 
treatment. 
 

SAP_001.pdf: 
Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 1 of 47
 
 
 
STATISTICAL ANALYSIS PLAN 
A Phase 1b study to assess the safety, tolerability and antimalarial activity of 
MMV533 against Plasmodium falciparum 3D7 blood stage infection in healthy 
volunteers 
 
Protocol No.: MMV_MMV533_20_01 
Product Code: MMV533 for oral administration 
 
PREPARED FOR:    Medicines for Malaria Venture (MMV)  
                                  ICC-Block G 3rd Floor 
                                  20, Route de Pré-Bois 
                                  1215 Geneva 15 
                                  Switzerland 
                                  Phone: +41 22 555 03 00 
 
PREPARED BY:       Southern Star Research 
 
Level 1, 1 Merriwa St 
 
Gordon, NSW, 2072  
 
Australia  
 
DATE OF ISSUE:     28 November 2022  
 
 
VERSION/STATUS: Final Version 1.0 
 
      AUTHOR:         Ray Lin 
 
 
 
 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 2 of 47
 
SAP APPROVAL 
 
By my signature, I confirm that this SAP has been reviewed and has been approved for use 
on the MMV_MMV533_20_01 study: 
 
Name 
Title / Company 
Signature 
Date 
Overarching sections 
(sections 1 to 7 and 14 to 
17), section 8 
(Demographics), section 
12 (Safety), and section 
13 (Exploratory 
parameters 
 
Ray Lin 
 
Associate Director, 
Statistics / 
Southern Star 
Research Pty Ltd. 
 
 
Section 9 (PK) 
 
Maja Szramowska 
Lead 
Pharmacokineticist 
PharmaKinetic Ltd. 
 
 
Section 10 (PD-PRR 
Endpoints) 
 
Authored by: 
Stacey Llewellyn  
Biostatistician,  
QIMR Berghofer 
Medical Research 
Institute 
 
 
Section 10 (PD-non-PRR 
Endpoints) 
 
Section 11 (PKPD) 
 
Dr Sam Jones 
PKPD Manager 
Medicines for 
Malaria Venture 
 
 
 
Approved by 
 
Stephan Chalon 
VP Experimental 
Medicine & Clinical 
Pharmacology/ 
Medicines for 
Malaria Venture 
 
 
Approved by 
 
Denis Gossen  
Consultant, 
Clinical Sciences/ 
Medicines for 
Malaria Ventures 
 
 
 
Electronically
signed by: Ray Lin
Reason: I have
authored this
document.
Date: Nov 28, 2022
14:01 GMT+11
28-Nov-2022
Maja Szramowska
Electronically signed by:
Maja Szramowska
Reason: I have reviewed
and approve this
document.
Date: Nov 29, 2022
07:39 GMT
29-Nov-2022
Stacey Llewellyn
Electronically signed
by: Stacey Llewellyn
Reason: I have
authored this
document.
Date: Nov 30, 2022
15:23 GMT+10
30-Nov-2022
Sam Jones
Electronically signed
by: Sam Jones
Reason: I have
reviewed and
approve this
document.
Date: Dec 1, 2022
08:37 GMT+1
01-Dec-2022
Stephan Chalon
Electronically signed
by: Stephan Chalon
Reason: I have
reviewed this
document.
Date: Dec 1, 2022
09:07 GMT+1
01-Dec-2022
Denis Gossen
Electronically signed
by: Denis Gossen
Reason: I approve
this document.
Date: Dec 1, 2022
09:37 GMT+1
01-Dec-2022


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 3 of 47
 
Table of contents 
 
1. 
INTRODUCTION .................................................................................................................... 8 
2. 
PROJECT OVERVIEW ............................................................................................................ 9 
 
Study Design ............................................................................................................................. 9 
 
Schema ................................................................................................................................... 10 
 
Objectives ............................................................................................................................... 11 
 
Endpoints ................................................................................................................................ 11 
 
Sample Size ............................................................................................................................. 12 
 
Treatment Assignment and Randomisation ........................................................................... 12 
3. 
STATISTICAL CONSIDERATIONS ......................................................................................... 13 
 
Data Capture........................................................................................................................... 13 
 
Statistical Programming ......................................................................................................... 14 
4. 
ANALYSIS SETS ................................................................................................................... 16 
 
Analysis Set Descriptions ........................................................................................................ 16 
5. 
PROTOCOL DEVIATIONS..................................................................................................... 16 
6. 
Volunteer DISPOSITION ..................................................................................................... 18 
 
Disposition .............................................................................................................................. 18 
 
Clinical Trial Unit Admission, Confinement and Discharge .................................................... 18 
7. 
DEMOGRAPHIC AND BASELINE INFORMATION ................................................................ 18 
 
Demographics ......................................................................................................................... 18 
 
Medical History ....................................................................................................................... 18 
 
Prior Medications ................................................................................................................... 19 
 
Eligibility ................................................................................................................................. 19 
 
Drug Screen ............................................................................................................................ 19 
 
Alcohol Screen ........................................................................................................................ 19 
 
SARS-CoV-2 ............................................................................................................................. 19 
 
Beck Depression Inventory ..................................................................................................... 19 
8. 
TREATMENT EXPOSURE ..................................................................................................... 20 
 
Study Drug Administration ..................................................................................................... 20 
9. 
PHARMACOKINETIC NON COMPARTMENTAL ANALYSIS (PK NCA) ................................... 21 
 
Parameters calculated ............................................................................................................ 21 
 
Methodology .......................................................................................................................... 21 
 
Bioanalytical Concentrations and PK NCA Parameters Data Reporting ................................. 23 
 
Bioanalytical and PK NCA Parameters Listings ....................................................................... 24 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
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Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 4 of 47
 
 
Bioanalytical and Pharmacokinetic Summary Tables ............................................................. 24 
 
Bioanalytical and Pharmacokinetic Figures ............................................................................ 24 
 
Pharmacokinetic Software ..................................................................................................... 24 
10. 
PHARMACODYNAMICS (PD)........................................................................................... 25 
 
Parameters ............................................................................................................................. 25 
 
Responsibility.......................................................................................................................... 25 
 
Source of Data ........................................................................................................................ 25 
 
Data Handling ......................................................................................................................... 25 
 
Parasite Clearance Kinetics and Recrudescence .................................................................... 26 
 
Parasite life-stage analysis...................................................................................................... 29 
 
Software ................................................................................................................................. 29 
 
Presentation of results ........................................................................................................... 30 
11. 
Pharmacokinetics/pharmacodynamics MODELLING ..................................................... 31 
 
Overview ................................................................................................................................. 31 
 
Sources of data ....................................................................................................................... 31 
 
Data handling ......................................................................................................................... 31 
 
Methods ................................................................................................................................. 32 
 
PKPD endpoints ...................................................................................................................... 35 
 
Software ................................................................................................................................. 37 
12. 
SAFETY ............................................................................................................................ 38 
 
Adverse Events ....................................................................................................................... 38 
 
Concomitant Medication ........................................................................................................ 41 
 
Laboratory .............................................................................................................................. 42 
 
Vital Signs ............................................................................................................................... 43 
 
Body Measurements .............................................................................................................. 44 
 
Physical Examination .............................................................................................................. 44 
 
12-lead ECG ............................................................................................................................ 44 
 
Malaria Clinical Score ............................................................................................................. 45 
 
Software ................................................................................................................................. 45 
13. 
Exploratory Parameters ................................................................................................. 46 
 
Parameters ............................................................................................................................. 46 
 
Biostatistical methods ............................................................................................................ 46 
 
Software ................................................................................................................................. 46 
14. 
CHANGES TO THE PLANNED ANALYSIS .......................................................................... 46 
15. 
INTERIM AND FINAL ANALYSIS ...................................................................................... 46 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 5 of 47
 
16. 
REFERENCES ................................................................................................................... 46 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 6 of 47
 
ABBREVIATIONS 
 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine Aminotransferase 
APR28 
Adequate Parasitological Response Rate at Day 28 
APR28 CSoff 
Adequate parasitological response at day 28 clinical symptoms off 
APR28 CSon 
Adequate parasitological response at day 28 clinical symptoms 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUClast 
Area under the curve from time 0 to last measurable concentration 
AUCinf 
Area under the curve from time 0 to infinity 
β-HCG 
β-Human Chorionic Gonadotropin 
BDI 
Beck Depression Inventory 
BMI 
Body Mass Index 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CK 
Creatine Kinase 
CL/F 
Apparent Oral Clearance 
Cmax 
Maximum plasma concentration observed 
COVID-19 
Corona virus disease 2019 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
Diastolic Blood Pressure 
DTS 
Data Transfer Specification 
ECG 
Electrocardiography 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data capture 
EOS 
End of Study 
ETF CSoff 
Early treatment failure clinical symptoms off 
ETF CSon 
Early treatment failure clinical symptoms on 
FAS 
Full Analysis Set 
FSH 
Follicular Stimulating Hormone 
G6PD 
Glucose-6-phosphatase 
GGT 
Gamma Glutamyl Transpeptidase 
HBsAg 
Hepatitis B Surface Antigen 
HEENT 
Head, Eyes, Ears, Nose, Throat 
HIV 
Human Immunodefiniciency Virus 
HR 
Heart Rate 
IBSM 
Induced Blood Stage Malaria 
IC50 
Investigational Medicinal Product 
IMP 
Investigational Medicinal Product 
INR 
International Normalized Ratio 
LCF28 
Late clinical failure at day 28 
LDH 
Lactate Dehydrogenase 
LOQ 
Limit of Quantification 
LPF28 CSoff 
Late parasitological failure at day 28 clinical symptoms off 
LPF28 CSon 
Late parasitological failure at day 28 clinical symptoms on 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum Inhibitory Concentration 
MPC90 
Minimal Parasiticidal Concentration 
ND 
Non-Detect 
PC 
Pharmacokinetics Concentration 
PCSA 
Potential Clinically Significant Abnormality 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 7 of 47
 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PKPD 
Pharmacokinetic-pharmacodynamic 
PN 
Preferred Name 
PRR48 
Parasite Reduction Ratio Over 48 hours 
PT 
Preferred Term 
Pt1/2 
Parasite Clearance Half-Life 
QIMRB 
QIMR Berghofer Medical Research Institute 
qPCR 
Quantitative Polymerase Chain Reaction 
QPID 
Queensland Paediatric Infectious Diseases 
qRT-PCR 
Quantitative Reverse Transcriptase Polymerase Chain Reaction 
QTcB 
Corrected QT interval with Bazett’s Formula 
QTcF 
Corrected QT interval with Fridericia’s Formula 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SBP 
Systolic Blood Pressure 
SBQ 
Swiss BioQuant Central 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SE 
Standard Error 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
SSR 
Southern Star Research 
t1/2 
Half-Life 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time to Reach Maximum Plasma Concentration 
VIS 
Volunteer Infection Study 
Vz/F 
Apparent Volume of Distribution after Extravascular Administration 
WOCBP 
Women of Child Bearing Potential    
WHODrug 
World Health Organization Drug Dictionary 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 8 of 47
 
1. INTRODUCTION 
The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of 
the data from the MMV_MMV533_20_01 study. 
 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. In addition, post hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data.  Any 
post hoc, or unplanned, exploratory analyses performed will be clearly identified as such in 
the final CSR. 
 
Any significant changes from planned analyses will also be described in the final CSR. 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 9 of 47
 
2. PROJECT OVERVIEW 
 Study Design 
The study is a Phase 1b, open label, adaptive study using the Induced Blood Stage Malaria 
(IBSM) model to characterise the antimalarial activity of a single oral dose of the IMP MMV533 
using pharmacokinetic and pharmacodynamic parameters and to further assess the safety and 
tolerability of MMV533.  
 
The study will be conducted in healthy malaria naive adult volunteers infected with Plasmodium 
falciparum 3D7, in one cohort of approximately 12 volunteers (all receiving active treatment). 
From an operational perspective, the full cohort may be conducted in subgroups of up to 6 
volunteers. Volunteers will be enrolled within a 28 day screening period to ensure volunteers 
meet all the inclusion criteria and none of the exclusion criteria.  
 
On Day -8 (8 days prior to IMP administration), volunteers will attend the clinical unit to be 
inoculated with the malaria challenge agent containing approximately 2,800 viable human 
erythrocytes infected with P. falciparum 3D7 parasites. Parasitaemia will be monitored on an 
outpatient basis daily on Day -4, and then twice daily on Day -3, Day -2 and until admission to 
the clinical unit on Day -1 for eligibility check and confinement.  
 
Volunteers will be administered IMP on Day 1 and will have safety monitoring and blood 
sampling for parasitaemia monitoring and PK analysis on an inpatient basis for at least 108 
hours post-IMP administration. Volunteers will be discharged from the clinical unit after review 
of ECG, vital signs, clinical and laboratory tests safety data by the Principal Investigator or 
delegate, and will then attend the clinical unit on an outpatient basis regularly for continued 
safety monitoring and blood sampling for parasitaemia monitoring and PK analysis.  
 
Volunteers will be administered mandatory malaria rescue medication (Malarone as first-line 
treatment) at Day 21±3, or earlier if there is failure to clear parasites or recrudescence (both 
defined in the study protocol) and/or at the discretion of the Principal Investigator or delegate. 
End of study (EOS) will be on Day 28±3. To be considered completed, volunteers must have 
had at least two consecutive negative malaria18S qPCR results (including EOS result) and 
must have completed their course of anti-malarial rescue medication. Please refer to flow chart 
2.2 below for the schedule of activities.   
 
In the event of recrudescence, blood samples will be collected prior to rescue treatment to 
culture parasites for drug resistance testing. 
 
 
 
 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 10 of 47 
 
 Schema 
 
 


Protocol Number: MMV_MMV533_20_01 
 
28 November 2022 
Document status: Final SAP Version 1.0 
 
BM S01-A, v3.0 
Statistical Analysis Plan 
Effective:  17/SEP/2020 
CONFIDENTIAL 
 
Page 11 of 47
 
 Objectives 
2.3.1 Primary Objective 
• To characterize the activity of single oral doses of MMV533 on clearance of Plasmodium 
falciparum 3D7 blood stage parasites from the blood in an IBSM model 
2.3.2 Secondary Objective(s) 
• To characterize the safety and tolerability of single oral doses of MMV533 administered 
after IBSM challenge 
• To characterize the pharmacokinetic (PK) parameters of single oral doses of MMV533 
after IBSM challenge (parent drug and metabolites) 
• To determine the relationship between MMV533 PK and asexual blood-stage parasitaemia 
in an IBSM model 
2.3.3 Exploratory Objective(s) 
• To investigate drug resistance of P. falciparum 3D7 in volunteers experiencing 
recrudescence after MMV533 administration 
• To determine if gametocytes appear in the blood of volunteers infected with P. falciparum 
3D7 after MMV533 administration  
 Endpoints 
2.4.1 Primary Endpoint(s) 
• 
Parasite reduction ratio over 48 hours (PRR48) 
• 
Parasite clearance half-life (Pt½) 
• 
Lag phase 
• 
Number of volunteers whose parasitaemia levels fall below limit of quantification (LOQ) 
following treatment with IMP 
• 
Number of volunteers with recrudescence of parasitaemia. 
• 
Time to recrudescence  
2.4.2 Secondary Endpoint(s) 
 Safety 
• 
Assessment of AEs/TEAEs; two phases will be defined: one corresponding to the 
inoculation phase (ie, 8 days before IMP administration), and one corresponding to 
treatment phase (i.e. 28 days after IMP administration) 
• 
Clinical laboratory evaluations including haematology, biochemistry, coagulation, 
urinalysis. 
• 
Vital signs (body temperature, blood pressure and heart rate supine), 
• 
12-lead ECG (automatic reading): RR, HR, PR, QRS, QT, QTc measured by on site-device. 
 Pharmacokinetics of MMV533 and metabolites  
• 
Plasma parameters: at least Cmax, tmax, AUClast, AUCinf, AUC0-168, %AUCextrap, t½, Lambda-z, 
CL/F (parent only), Vz/F (parent only); plasma ratios (metabolite to parent drug) of Cmax, 
AUClast and AUCinf. 
 Pharmacokinetics-Pharmacodynamics  
• 
The PK/PD relationship between MMV533 plasma concentrations and blood stage asexual 
parasitaemia will be determined  


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• 
Other key parameters will be derived from the PKPD model including minimum inhibitory 
concentration (MIC), the minimal parasiticidal concentration (MPC90), and the parasite 
reduction rate in 48 h (PRR48). 
2.4.3 Exploratory Endpoint(s) 
• 
Perform in vitro drug sensitivity testing determining the 50% inhibitory concentrations (IC50) 
and the percentage surviving parasites 
• 
Presence or absence of gametocytaemia (i.e, binary qualitative assessment) following a 
single dose of MMV533 
 Sample Size 
Up to approximately 12 volunteers (all receiving MMV533). The sample size of the study is 
based on experience from previous Phase 1 IBSM trials (refer to the Blood stage Plasmodium 
falciparum challenge agent P. falciparum 3D7 Investigator’s Brochure). 
 Treatment Assignment and Randomisation 
The study is open label and is not randomised. The cohort will be composed of up to 6 dose 
levels with a minimum of 2 volunteers per dose level. Details will be provided in the Pharmacy 
Manual. 
 
All volunteers will be administered IMP on Day 1, eight days after inoculation with the malaria 
challenge agent when parasitaemia of majority of volunteers are expected to be between 
approximately 5,000 - 25,000 parasites/mL (unless rescue medication is administered). If 
parasitaemia levels and/or symptoms monitored after inoculation suggest that unacceptable 
levels of parasites/mL and/or malaria symptoms could be achieved/observed on Day 1, the 
Principal Investigator or delegate may decide to administer IMP or rescue medication before 
Day 1. Such a decision will not be considered a protocol deviation for obvious safety reasons 
and will be recorded in the source documentation.  
2.6.1 Replacement of Withdrawn/Discontinued Volunteers 
Volunteers who have signed the informed consent form but have not received the trial 
intervention (i.e., inoculation with the malaria challenge agent) may be replaced.  
 
The replacement of volunteers who have received any trial intervention (inoculation with the 
malaria challenge agent only or inoculation and IMP) and withdraw or are withdrawn or 
discontinued from the trial, must be discussed between the Principal Investigator and the 
Sponsor.   
 
If more than two discontinuations due to non-safety related reasons occur, additional volunteers 
may be recruited to replace the discontinued volunteers on agreement with the study Sponsor. 
 


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3. STATISTICAL CONSIDERATIONS 
Data analysis will be performed according to the Sponsor’s representative Standard Operating 
Procedures (SOPs). 
 
The general analytical approach for all endpoints will be descriptive in nature.  All summaries 
will present the data by cohort group as well as by all volunteers combined.  
 
Unless otherwise stated, the following statistical approaches will be taken: 
 
Continuous variables:   
Descriptive statistics will include the number of non-missing 
values, mean, standard deviation (SD), median, minimum, and 
maximum.  The minimum and maximum values will be presented 
to the same number of decimal places as recorded in the raw 
data; mean, median, and SD will be presented to one more 
decimal place than the raw data. 
 
Categorical variables:   
Descriptive statistics will include frequency counts and 
percentages per category.  Percentages will be rounded to 
one decimal place, with the denominator being the number of 
volunteers in the relevant population with non-missing data. 
 
Imputation:   
No missing data will be imputed. 
 
Confidence intervals (CIs):   CIs will be two-sided and will use 95% confidence levels.  Any 
analyses requiring significance testing will use a two-sided test at 
the 5% significance level. 
 
Unscheduled Visits 
Unscheduled visits will be excluded from summary tables. 
 
Early termination visit 
Assessments conducted at Early Termination will be excluded 
from visit-based summary tables. 
 Data Capture 
3.1.1 Database 
The primary method of data collection is via the study database, developed within the chosen 
Electronic Data Capture (EDC) platform, IBM Clinical Development. The database has been 
designed based on the final protocol, the system/core configuration, electronic Case Report 
Form (eCRF) specifications and/or mock eCRF and consistency check specifications. 
 
Data will be entered directly into the EDC system. Site-collected data will be entered directly 
from source notes at the site and will be verified by Clinical Research Associates (CRAs) to 
ensure data integrity.  
 
Refer to the Data Management Plan for further details. 
3.1.2 Third Party Data 
 Safety Laboratory 
Central safety laboratory data will be received from SydPath Clinical Trials as specified in the 
Data Transfer Specification. At minimum a single transfer will be delivered prior to database 
lock and reconciled against CRF data. Following successful reconciliation and resolution of any 
data issues, the data will be incorporated into the End of Study analysis. 


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No unit conversion of laboratory data will be performed. 
 PK Laboratory (SBQ, Switzerland) / Pharmakinetic 
PK samples will be analysed by Swiss BioQuant Central (SBQ) and PK parameters will be 
derived by Pharmakinetic.  Final PK assay data will be transferred to SSR, as specified in the 
SBQ DTS, for incorporation into the PC SDTM. 
 
PK analysis then will be performed by Pharmakinetic where PK parameters will be derived 
following receipt of a merge file as agreed in the BioA data transfer specification. 
 PD Laboratory (Queensland Paediatric Infectious Diseases (QPID)) / Queensland 
Institute of Medical Research (QIMR)) 
PD samples (i.e. parasitemia levels) will be analysed by QPID and the PD parameters will be 
calculated by QIMR (See Section 10 for PD parameters calculation). Final PD assay data will 
be transferred to SSR, as specified in the QIMR DTS, for incorporation into the Microbiology 
Specimens (MB) SDTM. 
 PK/PD Analysis  
PK/PD analysis will be performed by MMV, Pharmacometrics. SSR will be required to provide 
the PK concentration data, parasitemia, as well as any CRF datasets required to perform the 
PKPD analyses (e.g. demographics, drug administration data).   
 Statistical Programming 
3.2.1 Programming Specifications 
Programming specifications will be prepared to detail the SAS programming of CDISC (SDTM 
and ADaM) datasets and listings, tables and figures. 
3.2.2 Baseline 
Baseline will be defined as the last scheduled observation prior to the first IMP administration.  
3.2.3 Change from Baseline 
Change from Baseline will be calculated as: 
 
𝐶ℎ𝑎𝑛𝑔𝑒 𝑓𝑟𝑜𝑚 𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒= (𝑝𝑜𝑠𝑡𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒) −𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒 
3.2.4 Study Day 
Study Day will be derived as the number of days relative to date of first administration of study 
drug, where the day of first administration = 1 
 
Study Day will be calculated as: 
 
𝑆𝑡𝑢𝑑𝑦 𝐷𝑎𝑦= (𝐴𝑠𝑠𝑒𝑠𝑠𝑚𝑒𝑛𝑡 𝐷𝑎𝑡𝑒−𝐹𝑖𝑟𝑠𝑡 𝑆𝑡𝑢𝑑𝑦 𝐷𝑟𝑢𝑔 𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝐷𝑎𝑡𝑒) + 1 
3.2.5 CDISC 
Study data (including CRF data and data transfers received from third parties) will be mapped 
to Clinical Data Interchange Standards Consortium (CDISC) compliant datasets, including 
Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM). 
 
Reviewer guides and define files are NOT required.  


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3.2.6 Listings, Tables and Figures 
Listings, tables and figures will be delivered as individual .rtf files in accordance with the mock 
listings, tables and figures. 
 
Data listings will present all data, with volunteers grouped by cohort.  
3.2.7 Treatment Groups 
Tabulations will summarise data by the following cohort groups:  
• 
MMV 533 (20 mg) 
• 
MMV 533 (35 mg) 
• 
MMV 533 (100 mg) 
• 
MMV 533 (160 mg) 
• 
Overall 
 
 
 
 


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4. ANALYSIS SETS 
In the first instance, two (2) analysis sets will be used for the analyses: Full Analyses Set (FAS), 
and Safety Set.   
The number of volunteers in each analysis set will be summarised, with a corresponding listing. 
 Analysis Set Descriptions 
4.1.1 Full Analysis Set 
The Full Analysis Set (FAS) will consist of all enrolled volunteers.  The FAS will be used to 
assess all volunteer disposition, baseline, demographic and protocol deviation data. 
4.1.2 Safety Set 
The Safety Set will include all enrolled volunteers who received at least one dose (full or partial) 
of IMP. The Safety Set will be used to assess all safety data. 
4.1.3 PK Analysis Set 
The PK Analysis Set will consist of those participants in the safety set who have sufficient blood 
samples taken for at least one of the PK variables to be calculated and who experienced no 
protocol deviations with relevant impact on PK data. The PK Analysis Set  will be used for the 
PK analyses. Should an adverse event, for example, vomiting within 4 hours of IMP dosing 
occur and be deemed detrimental to the data quality, additional subsets may be invoked, and 
those subjects be omitted from the summary statistics. This will be confirmed with the sponsor 
if applicable.  
4.1.4 PD Analysis Set 
The PD Analysis Set will include all volunteers inoculated with the malaria challenge agent and 
who develop parasitaemia detectable by qPCR, received at least one dose of IMP, and have 
no protocol deviations or other circumstances that would exclude them from the PD analysis. 
4.1.5 PK/PD Analysis Set 
The PK/PD Analysis Set will include all volunteers from the PK set and all volunteers from the 
PD set for the VIS study in the disposition summary. While performing the PK/PD analysis, it 
will also contain all volunteers from the FIH study MMV_MMV533_19_01_FIH with at least one 
PK concentration. 
4.1.6 Inoculation Set 
The Inoculation Set will include all volunteers inoculated with the P. falciparum challenge agent. 
5. PROTOCOL DEVIATIONS 
Analysis Set: FAS 
All protocol deviations will be listed. A protocol deviation summary table will present the total 
number of protocol deviations as well as the number of volunteers who reported at least one 
protocol deviation, broken down by deviation type, relationship to COVID-19, and type. 
5.1.1 Definition of variables 
• 
Date deviation detected 
• 
Date of deviation 
• 
Deviation classification 
o Minor 
o Major 


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• 
Deviation related to COVID-19 
o Yes 
o No 
• 
Deviation type 
o Informed consent 
o Eligibility 
o Visit not done 
o Visit performed out of window 
o Study procedure not done 
o Study procedure done out of window 
o Safety reporting 
o Investigational product 
o Privacy and data protection 
o Concomitant medication 
o Other 
• 
Deviation description 
• 
Action taken 
• 
Outcome 


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6. VOLUNTEER DISPOSITION 
Analysis Set: FAS 
 Disposition 
A listing of volunteer disposition will be presented: 
• 
Date of informed consent 
• 
Date of inoculation 
• 
Date of IMP administration 
• 
Date of rescue medication administration 
• 
Did the volunteer complete the study? 
• 
Date of completion / early withdrawal 
• 
Primary reason for early withdrawal (including instances where early termination was 
related to COVID-19) 
Detailed early withdrawal information will also be listed in a separate listing. 
If there are any deaths reported, a separate death listing will be prepared. 
The number and percentage of volunteers entering and discontinuing the study will be 
summarised by cohort and overall along with the reason for discontinuation. The volunteer 
disposition summary table will include: 
• 
Number of volunteers signed informed consent 
• 
Number of volunteers who received IMP  
• 
Number of volunteers who completed the full study 
• 
Number of volunteers withdrawn from the study early 
• 
Reason for early withdrawal 
 Clinical Trial Unit Admission, Confinement and Discharge 
All admission, confinement and discharge data will be listed 
7. DEMOGRAPHIC AND BASELINE INFORMATION 
Analysis Set: FAS 
 Demographics 
Demographic data will be listed for all enrolled volunteers and summarised by cohort and 
overall.  Data includes: 
• 
Age 
• 
Sex 
• 
Women of Child-bearing potential 
• 
Post-menopausal  
• 
Race 
• 
Ethnicity 
• 
Weight (kg) 
• 
Height (m) 
• 
BMI (kg/m2) 
 Medical History 
All medical history data will be listed, grouped by volunteers. 
 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and summarised by system organ class (SOC) and preferred term (PT).  


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 Prior Medications 
Prior medications are defined as any medication that is started before first inoculation with the 
malaria challenge agent, regardless of when it ended. If a medication has a missing or partial 
missing start/end date or time and it cannot be determined whether it was taken before IMP or 
concomitantly, it will be considered as prior and concomitant. Medications will be coded using 
WHODrug Global. 
 
Prior medications will be summarised by Anatomical Therapeutic Class (ATC) and preferred 
name (PN) and will also be listed. The summary tables will show the number and percentage 
of volunteers taking each medication by ATC and PN. 
 Eligibility 
Eligibility will be listed for all enrolled volunteers. 
 Drug Screen 
Drug screen data will be listed for all volunteers. 
 Alcohol Screen 
Alcohol screening data will be listed for all volunteers. 
 SARS-CoV-2  
Any positive SARS-CoV2 results will be listed. 
 Beck Depression Inventory 
Beck Depression Inventory (BDI-II) data will be listed for all volunteers, including answers to 
the individual questions as well as the total scores, which are auto-calculated within the CRF. 


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8. TREATMENT EXPOSURE 
Analysis Set: Safety Set 
 Study Drug Administration 
Volunteer exposure to the protocol-specified treatments (IMP, malaria challenge agent and 
rescue medications) will be listed and summarised by cohort and overall.   
 


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9. PHARMACOKINETIC NON COMPARTMENTAL ANALYSIS (PK NCA) 
Analysis Set: PK Analysis Set (see section 4) 
 
MMV533 (& metabolites - MMV022 and MMV023) PK parameters will be derived by 
PharmaKinetic Ltd. PK parameters will be calculated using non-compartmental methods from 
plasma concentration-time data and will be summarized using descriptive statistics. 
 Parameters calculated 
• Cmax: Maximum plasma concentration observed 
• tmax: Time to reach maximum plasma concentration 
• AUClast: Area under the curve from time 0 to last measurable concentration 
• AUC0-168: Area under the curve from time 0 to 168 hour 
• AUCinf: Area under the curve from time 0 to infinity 
• %AUCextrap: Percentage of AUC(0–inf) extrapolated beyond the last measurable 
concentration 
• t½: Half-life 
• Lambda-z: Slope of the apparent elimination phase 
• CL/F: Apparent Oral Clearance after extravascular administration (parent only) 
• Vz/F: Apparent volume of distribution after extravascular administration (parent only) 
• plasma ratios (metabolite to parent drug) of 
o Cmax 
o AUClast 
o AUCinf. 
 Methodology 
9.2.1 Source of data 
Plasma concentration of MMV533 and its metabolites, treatment and blood sampling 
information will be recorded and merged to produce PK concentration data for analysis. 
9.2.2 Imputation of Non-Numerical or Negative Values 
The imputation of non-numerical or negative values reported in the input data set will be 
performed as follows: 
• Predose sample times will be entered as zero 
• Values that are below the limit of quantification (BLQ) obtained prior to the Cmax will be 
entered as zero 
• Values that are BLQ after the Cmax will be treated as missing 
• Pharmacokinetically plausible concentration value(s) below LLOQ at time points between 
two measurable concentration values are replaced by the LLOQ/2 value, flagged and 
included in the PK evaluation.  
• Should partial AUCs be required then values that are BLQ after Cmax may be imputed as 
zero for these partial areas if lambda-z cannot be determined 
• Values that are quantifiable after at least 2 consecutive BLQ values after Cmax will be treated 
as missing for the calculation of PK parameters 
• Actual time from dose administration will be used for parameter estimation except for the 
pre-(first) dose data point which will be set to the nominal time of 0 hour. Data with missing 
time information will be discarded. 
• Values that are reported as “No Result” or “No Sample” etc. will be treated as missing 
9.2.3 Rules for Pharmacokinetic Parameter Estimation using WinNonlin 


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Plasma concentration vs time profiles of MMV533 and metabolites will be generated for each 
volunteer. Pharmacokinetic parameters will be estimated using standard Phoenix WinNonlin 
methods, details of which may be found in the documentation accompanying the WinNonlin 
software package. The following constraints will apply: 
 
Parameter Estimation 
Constraint 
Trapezoidal Method 
Linear trapezoidal linear/log interpolation method 
Number of Points used for Lambda-z 
At least 3, not including Cmax 
Minimum Requirements for AUC  
At least 3 consecutive quantifiable 
concentrations 
Dose 
Actual dose 
Sampling times 
Actual sampling times 
 
Where possible, the elimination rate constant (lambda-z) will be calculated for all volunteers. 
The value of lambda-z will be determined by the slope of the regression line of the natural log 
transformed concentrations vs time.  
 
The choice of data points for determination of lambda-z will be applied by the Phoenix software 
as a default method, the pharmacokineticist who may adjust the selection to provide a more 
appropriate fit and records of this will be documented in the software data. 
9.2.4 PK NCA Parameters Quality 
The following flags/footnotes may be applied to the pharmacokinetic parameters: 
Flag 
Footnote 
a 
Rsq of regression was <0.8 
b 
Period used for regression analysis was less than 2-fold the calculated half-life 
c 
Extrapolated portion of AUC0-inf >20% 
d 
Insufficient post-Cmax data points for estimation of lambda-z 
e 
Entire profile BLQ, no pharmacokinetic parameters could be calculated 
f 
Regression could not be fitted 
 
In the event that a reliable lambda-z cannot be determined, or the extrapolated portion of  
AUC0-inf is >20%, then the parameter estimates derived using lambda-z and/or AUC0-inf may be 
deemed unreliable and excluded from the summary statistics. Additional flags may be applied 
based on emerging data. 
9.2.5 Definition of Pharmacokinetic NCA Parameters 
The following pharmacokinetic parameters for MMV533 and metabolites in plasma will be 
estimated where possible and appropriate for each volunteer and treatment. 
 
The following pharmacokinetic parameters will be determined for each volunteer, analyte and 
study regimen as applicable. 
 


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Table 1 Pharmacokinetic Parameters and Reporting Specifications 
CDISC 
Term 
Parameter 
Definition 
DP 
or 
SF 
No. of 
DP/SF 
TMAX 
Tmax 
Time of maximum observed 
concentration 
DP 
2 
CMAX 
Cmax 
Maximum observed concentration 
SF 
3 
AUCLST 
AUClast 
Area under the curve from 0 time to the 
last measurable concentration 
SF 
3 
AUC168 
AUC0-168 
Area under the curve from 0 time to 168 
hours post dose 
SF 
3 
AUCIFO 
 
AUC0-inf 
Area under the curve from 0 time 
extrapolated to infinity 
SF 
3 
AUCPEO 
%AUCextrap 
Percentage of AUC(0–inf) extrapolated 
beyond 
the 
last 
measurable 
concentration 
DP 
2 
LAMZHL 
t1/2 
Apparent elimination half-life 
DP 
2 
LAMZ 
Lambda-z 
Slope of the apparent elimination phase 
DP 
4 
CLFO 
CL/F 
Total body clearance after extravascular 
administration (estimated for parent only) SF 
3 
VZFO 
Vz/F 
Apparent volume of distribution based on 
the terminal phase after extravascular 
administration (estimated for parent only) 
SF 
3 
MPCMAX 
Cmax,metab/ 
Cmax,parent 
plasma ratio (metabolite to parent drug) 
SF 
3 
MPAUCLST AUClast,metab/ 
AUClast,parent 
plasma ratio (metabolite to parent drug) 
SF 
3 
MPAUCIFO 
AUCinf,metab/ 
AUCinf,parent 
plasma ratio (metabolite to parent drug) 
SF 
3 
DP=decimal places 
SF=significant figures 
 Bioanalytical Concentrations and PK NCA Parameters Data Reporting 
All bioanalytical data will be listed and summarised according to the actual sampling timepoint.  
 
All pharmacokinetic NCA parameters generated will be listed and summarised. Where 
pharmacokinetic data fails to meet the defined criteria in Section 9.2.4  (PK NCA Parameters 
Quality) the affected results will be excluded from the descriptive statistics will be flagged as 
per exclusion reason. 


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 Bioanalytical and PK NCA Parameters Listings 
All bioanalytical and pharmacokinetic NCA parameters generated will be listed in individual 
tables according to the analyte and treatment. In addition, the sum of the moiety data will also 
be listed in individual tables according to treatment. The data listings will be generated as 
defined by the PK Concentration population. 
 Bioanalytical and Pharmacokinetic Summary Tables 
Bioanalytical and PK NCA parameters summary tables will be performed by SSR. 
 
Summary statistics (i.e., mean, median, SD, CV%, minimum, maximum, n, geometric mean, 
geometric SD and geometric CV%) will be calculated for PK results for each time point, 
parameter and treatment.  
 
All summary statistics (i.e., mean, median, SD, CV%, minimum, maximum and n) will be 
presented for all PK NCA parameters for plasma by treatment. Also, geometric mean, 
geometric SD and geometric CV% will be presented for all PK parameters (except Tmax) by 
treatment. The Tmax summary statistics will be provided as n, minimum, median, and maximum 
only. 
 
All the data summary tables will be generated as defined by the PK Analysis Set. Additional 
summary tables might be produced if required and requested. 
 Bioanalytical and Pharmacokinetic Figures 
All arithmetical mean plasma concentration vs. time curves will be produced by treatment on 
both linear/linear and log10/linear scales. 
 
All spaghetti plots of individual plasma concentrations against actual sampling times after 
dosing for each treatment will be produced on both a linear/linear and log10/linear scale. Each 
volunteer’s concentration profile will be represented on these plots with a different symbol and 
a legend will be included on the plots to define the symbols used. 
 Pharmacokinetic Software 
The estimation of pharmacokinetic parameters by non-compartmental analysis methods will be 
performed using Phoenix WinNonlin software (v8.3 or a more recent version, Certara USA, 
Inc., USA). 
 
SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA) will be used to analyze 
all PK concentration related statistical analysis. 
 
 
 


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10. PHARMACODYNAMICS (PD) 
Analysis Set: PD Analysis Set (see section 4) 
 Parameters 
• Parasite reduction ratio over 48 hours (PRR48) 
• Parasite clearance half-life (Pt½) 
• Lag phase 
• Number of volunteers whose parasitaemia levels fall below limit of quantification (LOQ) 
following treatment with IMP 
• Number of volunteers with recrudescence of parasitaemia. 
• Time to recrudescence 
• Presence or absence of gametocytaemia (i.e. binary qualitative assessment) following a 
single dose of MMV533 
• Total parasitaemia (measured by qPCR 18s) 
• Female gametocytemia (measured by RT-PCR pfs25) 
 Responsibility 
The statistical analysis on the following endpoints will be performed by QIMR: 
• Parasite reduction ratio over 48 hours (PRR48) 
• Parasite clearance half-life (Pt½) 
• Lag phase 
• Number of volunteers whose parasitaemia levels fall below limit of quantification (LOQ) 
following treatment with IMP 
• Number of volunteers with recrudescence. 
• Time to recrudescence  
• Presence or absence of gametocytaemia (i.e. binary qualitative assessment) following a 
single dose of MMV533 
 
Where the following endpoints will be performed by Southern Star Research: 
• Total parasitaemia (measured by qPCR 18s) 
• Female gametocytemia (measured by RT-PCR pfs25) 
 Source of Data 
All parasitaemia data will be generated by the Queensland Paediatric Infectious Diseases 
(QPID) laboratory and captured electronically using MARS (18S qPCR parasitaemia data). 
Quantitative parasite life-stage data (i.e. gametocytemia and ring-stage parasites) will be 
generated by the QPID laboratory and transferred electronically to QIMR Berghofer. 
 Data Handling 
Handling of replicates 
The data will be recorded as triplicate parasitaemia and duplicate gametocytaemia values for 
each subject at each timepoint. The replicate data will be summarised by calculating the 
geometric mean of the parasitaemia and parasite life-stage data (i.e. gametocytemia and ring-
stage parasites) transcript values per subject and timepoint, and will be log10 transformed for 
statistical analyses.    
 
Handling of missing data 
Missing parasitaemia or gametocytaemia data will not be imputed. For any replicates that were 
non-detects (ND), the value will be substituted with 1 parasite/mL prior to calculating the 


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geometric mean for parasitemia quantified from qPCR 18s, or as the LOD/2 of the assay for 
parasite life-stage data (i.e. gametocytemia and ring-stage parasites). 
 Parasite Clearance Kinetics and Recrudescence 
The Parasite Reduction Ratio (PRR) and corresponding parasite clearance half-life (Pt1/2) of 
asexual parasites is derived from the clearance rate of parasitaemia quantified using the Pf18s 
qPCR assay after administration of IMP. The analysis of PD response to investigational 
antimalarial therapy consists of: 
• calculating the optimal parasite clearance rate (slope coefficient from the log-linear decay 
regression of qPCR data) for each individual, then,  
• estimating dose specific parasite clearance rate and 95% confidence interval (CI) by 
calculating the weighted average slope estimate and corresponding standard error (SE) 
using an inverse-variance method. 
 
The data used for all model selection and fitting calculations is comprised of the log10 
transformed geometric mean of parasitaemia per timepoint per subject up to the first timepoint 
all parasitaemia replicates are ND. If during initial parasite clearance there are no samples ND 
for a subject, the last timepoint included in the analyses will be three timepoints after the 
minimum observed parasitemia value. All subsequent timepoints are set to ‘missing’ regardless 
of whether parasitaemia values increased afterwards due to potential recrudescence. 
Sensitivity analyses may be performed using other thresholds to determine parasite clearance, 
for example, but not limited to, the lower limit of quantification (LOQ) (i.e. the lower limit of the 
reportable range) of 32 parasites/mL or limit of detection of 111 parasites/mL [2], to assess 
robustness of PRR estimates. 
 
The PRR per 48 hours, PRR48, for asexual parasite will be estimated using the slope of the 
optimal fit of the log-linear relationship of the parasitaemia decay over time from IMP 
administration for each individual, as detailed in CTM QIMR SOP 41 and Marquart et al. [3].  
 
Table 2 Symbols and definitions of terms used in parasite clearance analysis (Part 1) 
Symbol 
Definition 
PRR48,i 
Individual specific Parasite Reduction Ratio per 48 h 
PRR48,D 
Dose specific Parasite Reduction Ratio per 48 h 
𝛽1,𝑖  
Slope coefficient of log10 parasitaemia vs. time profile for 
individual 𝑖 
𝑆𝐸𝛽1,𝑖  
SE corresponding to 𝛽1,𝑖 for individual 𝑖 
𝛽̅1,𝐷  
Dose specific average slope estimate 
𝑆𝐸(𝛽̅1,𝐷)  
Weighted SE of dose specific average slope estimate 
PCt½ 
Parasite clearance half-life 
 
Regression Modelling to Determine Optimal Fit  
A regression modelling approach to remove potential lag and/or tail phases of the parasitaemia 
decay profile will be used to determine the optimal log-linear decay regression. The algorithm 
considers removing parasitaemia data points in an iterative process from both ends of the 
parasitaemia curve, i.e. a combination of right censoring (removing values from the tail phase) 
and left censoring (removing values from the lag phase), and uses model selection techniques 
to find the optimal log-linear regression.  


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The algorithm to obtain the log-linear decay for each subject is based on the log-linear 
regression detailed in Equation (1), where Time is the number of hours since administration of 
antimalarial treatment (𝑇𝑖𝑚𝑒= 1, … , 𝑚), and 𝛽0 and 𝛽1 are the intercept and slope estimates, 
respectively.   
log10 𝑃𝑎𝑟𝑎𝑠𝑖𝑡𝑒𝑚𝑖𝑎= 𝛽0 + 𝛽1𝑇𝑖𝑚𝑒   (1) 
Based on the parasitaemia data for each subject, the iterative algorithm to determine the 
optimal log-linear decay for each subject is summarised in Table 3 Iteration process to 
determine the optimal log-linear decay curve. The iterative algorithm is continued until a 
minimum of four observations are available.  
The optimal log-linear regression model for a subject is deemed an appropriate fit if the overall 
model p-value < 0.001.  
 
Table 3 Iteration process to determine the optimal log-linear decay curve 
Step 1: For each subject, fit the full model - fit a linear regression (as defined by 
Equation 1) to all 𝑚 parasitaemia values of subject 𝑖  
Step 2: Fit two models: 
(a) Fit linear regression model to 𝑚−1 parasitaemia values, removing the first 
observation. 
(b) Fit linear regression model to 𝑚−1 parasitaemia values, removing the last 
observation. 
Step 3: Determine the best model of Step 2(a) and Step 2(b), defined as the model 
corresponding to the minimum overall model p-value.  
Step 4: Of the best model defined in Step 3, repeat Step 2 and Step 3 in an iterative 
process until a minimum of four observations. 
Step 5: Of the 𝑚−3 best models selected per iteration (including the full model (Step 
1)), the optimal model was defined by the minimum overall model p-value. 
 
Estimating Subject Specific PRR  
The slope and corresponding SE estimate of the optimal linear regression model is used to 
calculate the subject specific PRR48 estimate and corresponding 95% confidence interval 
(95% CI), as shown in Equation (2) and (3), respectively.  
𝑃𝑅𝑅48,𝑖= 10−48×𝛽1,𝑖                   (2) 
95% CI: 10−48(𝛽1,𝑖±1.96×𝑆𝐸(𝛽1,𝑖))  (3) 
where 𝛽1,𝑖 and 𝑆𝐸𝛽(1,𝑖) are the slope and corresponding standard error of the slope parameter 
of the optimal linear regression model, respectively. 
 
Estimating Dose Specific PRR (PRR48,D) 
Of the 𝑠 subjects with appropriate overall fit (p<0.001), the average PRR48 and corresponding 
95% CI for each cohort is estimated by using the inverse variance method to calculate the 


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weighted average linear regression slope (𝛽1
̅̅̅) and corresponding SE. The weighted average 
slope for 𝑠 subjects in the dose with appropriate overall fit is given by Equation (4): 
𝛽1
̅̅̅ =
∑
(𝑤𝑖×𝛽1,𝑖)
𝑠
𝑖=1
∑
𝑤𝑖
𝑛
𝑖=1 
, 𝑖= 1, … , 𝑠     (4) 
where the weight is the inverse of the squared standard error, 𝑤𝑖=
1
𝑆𝐸(𝛽1,𝑖)
2 . The standard error 
of 𝛽1
̅̅̅ is estimated as, 𝑆𝐸(𝛽1
̅̅̅) = √
1
∑
𝑤𝑖
𝑠
𝑖=1 
 .  
 
Therefore the dose specific PRR (PRR48,D) and corresponding 95% confidence interval is 
estimated as shown in Equation (5) and (6), respectively: 
 
𝑃𝑅𝑅48,𝐷= 10−48×𝛽1
̅̅̅̅                         (5) 
95% 𝐶𝐼:  10−48×(𝛽1
̅̅̅̅ ±1.96×𝑆𝐸(𝛽1
̅̅̅̅))      (6) 
 
PRR48 estimates will also be reported as log10(PRR48). 
 
Parasite Clearance Half Life 
The parasite clearance half–life (Pt½) will be derived from the optimal decay rate. The 
relationship between PRR48 and parasite clearance half-life (P𝑡½) is a simple transformation of 
the PRR48 as shown in Equation (7):  
𝑃𝑡½ = 𝑙𝑜𝑔10(2) × (
48 ℎ𝑜𝑢𝑟𝑠
𝑙𝑜𝑔10(𝑃𝑅𝑅48,𝑖)) =
log10(2)
−𝛽1,𝑖       (7) 
where PRR48,i is the parasitaemia  ratio estimated over a 48-hour interval that is subsequently 
transformed into a per hour clearance rate.  
 
Lag Phase 
The lag phase will be reported as the first Time included in the optimal log-linear decay curve 
(i.e. first non-left-censored timepoint), where Time is the number of hours since IMP 
administration. The lag phase will be reported in hours.  
 
Comparison of Dose Specific PRR48 
Comparisons of dose-specific PRRs may be performed. To determine whether there are 
differences between dose specific PRRs, an omnibus test for between group differences will 
be used. The test is used to assess whether there are differences in the weighted mean slope 
of the 𝐽 doses, using the test statistic shown in Equation (8), 
𝑄𝐵= ∑
𝑤𝑗. (𝛽̅𝑗. −𝛽̅. . )
2
𝐽
𝑗=1
~𝜒𝐽−1
2
                 𝑗= 1, … , 𝐽       (8) 
The weight for the  𝑗𝑡ℎ dose is denoted by 𝑤𝑗. = ∑
𝑤𝑖𝑗
𝑠𝑗
𝑖=1
 for subject 𝑖 with appropriate overall 
fit in dose 𝑗. The 𝛽̅𝑗. is the weighted average slope for dose 𝑗 as defined in Equation (9), and 𝛽̅.. 
is the weighted grand mean given by: 
𝛽̅. . =
∑
𝑤𝑗.𝛽̅𝑗.  
𝐽
𝑗=1
∑
𝑤𝑗.
𝐽
𝑗=1
         (9) 


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Post-hoc pair-wise comparisons can be calculated using the test statistic 𝑍𝐺=
𝐺
√𝑣𝐺 , where 𝐺 is 
the contrast (𝐺= 𝑐1𝛽̅1. + ⋯+ 𝑐𝐽𝛽̅𝐽) and 𝑣𝐺 is the variance of the contrast (𝑣𝐺=
𝑐12
𝑤1. + … +
𝑐𝐽
2
𝑤𝐽.). 
The p-value of the 𝐿 pair-wise comparisons can be calculated using the Scheffe method, by 
comparing 𝑍𝐺
2 to a chi-squared distribution with 𝐿−1 degrees of freedom. 
 
Characterising recrudescence 
 
The following parasite clearance and recrudescence characteristics will be summarized: 
• 
The number of volunteers and percentage of subjects in each dose group whose 
parasitaemia levels quantified using the Pf18s qPCR assay fall below the LOQ of 32 
parasites/mL, following treatment with IMP will be reported.  
• 
The number and percentage of subjects in each dose group who experience 
recrudescence following IMP administration and prior to scheduled Riamet® treatment 
period (Day 28±3) will be reported.  
• 
The time to recrudescence will be reported for subjects who experience recrudescence 
in each dose group. 
 
Initial parasite clearance is defined as a participant(s) parasitaemia, quantified by 18s qPCR, 
falling to non-detectable (ND) levels post IMP administration and pre administration of definitive 
antimalarial rescue medication. Therefore, the time of initial parasite clearance is the time-point 
of the first measurement post-IMP administration and pre administration of definitive 
antimalarial rescue medication where parasites are ND.  
 
Failure of initial parasite clearance is defined for a participant(s) when parasites do not fall to 
ND levels post IMP administration and pre administration of definitive antimalarial rescue 
medication. Note that in such cases, rescue medication will be administered as per the study 
protocol. 
  
Recrudescence can only be defined for a participant(s) for whom initial parasite clearance 
occurred. In other words, a participant(s) defined as failure of initial parasite clearance cannot 
also be defined as a recrudescence. Time to recrudescence is then defined as having occurred:  
o At the time-point that most closely precedes the time-point at which ≥5,000 
blood stage parasites/mL is reached, and where parasites ≥LOQ (32 
parasites/mL) or if parasites are not ≥LOQ, the time-point where parasites are ≥ 
the minimum recorded value for that participant.  If no time-point preceding the 
time-point of ≥5,000 blood stage parasites/mL exists where parasites are ≥ their 
minimum value following IPC, use the first time-point at which ≥5,000 blood 
stage parasites/mL is reached for the time of recrudescence. 
 
 Parasite life-stage analysis 
Parasite life-stage data including ring-stage parasites, male gametocytes and female 
gametocytes will be quantified using qRT-PCR targeting sbp1, pfs25, and pfMGET, 
respectively. Parasite life-stage data (pfs25, pfMGET and sbp1 qRT-PCR) will be presented 
for each assay per timepoint as the number and percentage of individuals within a dose group 
that have any detectable gametocytaemia or ring stage parasites after IMP administration. 
 Software 
Data manipulation and data analyses for all pharmacodynamic data to be analyzed by QIMR 
will be performed using R (version 4.1.0 or higher). 
 


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Data manipulation and data analyses for all pharmacodynamic data to be analyzed by SSR will 
be performed using SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA).  
 Presentation of results 
Individual values for total parasitemia (18S qPCR) and parasite life cycle stages (pfs25, 
pfMGET and sbp1 qRT-PCR) with nominal timepoints will be plotted and actual sampling times 
will be presented in data listings for all subjects. Non-detects (ND) will be flagged. The data will 
be presented as the geometric mean of triplicate (total parasitaemia data) or duplicate (parasite 
life- stage data) values for each subject at each timepoint. 
A full report on the pharmacodynamic data analysis provided by QIMRB will be included in the 
appendices of the CSR.  
 


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11. PHARMACOKINETICS/PHARMACODYNAMICS MODELLING 
Analysis Set: PK/PD Analysis Set (see section 4) 
 Overview 
Two stage approach: 
1. Estimate the PK parameters by fitting a PK model and relevant covariates to the 
individual PK concentrations 
2. Estimate the PD parameters by fitting a PKPD model to the asexual parasitemia 
observations using the individual PK parameters as regressors  
 Sources of data 
The PK/PD dataset will contain the individual information on the size of the inoculum, date and 
time of its administration; doses of MMV533 administered with date and time of administration; 
plasma PK concentrations of MMV533 and its metabolites (MMV022 and MMV023) with date 
and time of blood sampling; triplicate total parasitemia counts by 18S qPCR with date and time 
of blood sampling; gametocytemia counts by qRT-PCR pfs25; ring stage counts if relevant; and 
typical covariates such as age, height, sex and race.    
 
The PK/PD dataset will contain the data from the current VIS study MMV_MMV533_20_01 and 
from the past MMV_MMV533_19_01_FIH study.  
 
The PK/PD dataset for MMV_MMV533_20_01 will be prepared by SSR in the MMV format 
from the database. The PK/PD dataset for MMV_MMV533_19_01_FIH will be prepared by 
ClinBay.   
 Data handling 
11.3.1 Master PK/PD dataset 
Data from study MMV_MMV533_20_01_VIS will contain information on the individual MMV533 
doses, MMV533 PK concentrations, the triplicated parasitemia levels, gametocyte data and 
typical covariates such as age, height, weight, sex and race. Data from study 
MMV_MMV533_19_01_FIH will be added so as to increase the number of individuals with PK 
profiles.  
 
A master dataset will be assembled formatted according to the MMV dataset standard. (cf., 
"MS_IQdataset_V4_20210219.docx"). Plasma concentration will be in ug/mL, total parasite 
levels in counts/mL, and doses in mg. Gametocyte data is in copies/uL.  
 
Parasite data after the first administration of rescue medication is flagged by setting the 
IGNORE column to "Rescued". The time in hours is relative to the (first) MMV533 administration 
time. Gametocyte data will be converted to parasite counts following the instructions in 
"Analyzing RNA data by K.Collins Nov2017.docx". Total counts of parasites were flagged to be 
ignored (by setting the column IGNORE to "gametocytes") if counts of gametocytes exceeded 
10% of total counts.  
 
A general analysis dataset will then be created from the master dataset. The general dataset 
will contain the following observations: MMV533 plasma concentrations, total parasite count, 
as well as counts of gametocytes. In addition, dosing records for P. falciparum inoculation, 
MMV533 administration and rescue medication administration will be defined.  
 
The following covariates will be included as additional columns in the general dataset  
• 
DOSELEVEL: the dose amount 


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• 
DOSEMULT: the number of doses 
• 
WT0: body weight (kg) 
• 
AGE: age (years) 
• 
SEX: sex (male or female) 
• 
Infection status (for all volunteers from MMV_MMV533_20_01_VIS infection status will 
be positive; For all volunteers from MMV_MMV533_19_01_FIH infection status will be 
negative.) 
• 
PLbase: The model baseline parasitemia value – the geometric mean of parasite counts 
at time of first MMV533 dose.  
11.3.2 PK modelling dataset 
Observations below the lower limit of quantification (LLOQ) will be censored by setting the 
CENS column for these observation records to 1 and setting the corresponding dependent 
variable (DV) column to the LLOQ (→ M3 method). Observation records with missing values 
and records with missing times will be ignored. Records flagged to be ignored will be removed 
from the dataset. Observations not analyzed in the PK modelling (i.e., all parasite count 
records) will be removed. Consequently, the PK modelling NLME dataset will contain only 
MMV533 dosing records and MMV533 plasma concentration records. 
11.3.3 PD modelling dataset 
Observations below the LLOQ will be censored by setting the CENS column for these 
observation records to 1 and the corresponding DV value to the LLOQ, i.e., 10 p/mL (→ M3 
method). Total and viable counts of parasites for which counts of gametocytes exceeded 10% 
of total counts are flagged to be ignored (by setting the column IGNORE to "gametocytes"). 
Observation records with missing values and records with missing times will be ignored. 
Records flagged to be ignored will be removed from the dataset. Observations not analysed in 
the PD modelling analysis (i.e., concentration records) will be removed. Consequently, the  PD 
modeling NLME dataset will contain only MMV533 dosing records and total parasite counts. 
 
The total and viable parasite counts will be log-transformed for the PD modelling and estimated 
individual PK model parameters will be added to the dataset as regressors. 
 Methods 
Population models of the PK and PD will be developed in a step-wise manner. 
1. 
A population PK model will be developed to obtain individual PK parameter estimates 
based on which the individual PK profiles are described well. 
2. 
A parasite growth model (parasite growth rate and deviation of parasitemia at inoculation 
from parasitemia at treatment administration) will be estimated from the total parasite 
counts before treatment administration. Estimation of typical and individual PD parameters 
will be performed with IQRtools SysFit. Other appropriate growth models, e.g. an 
oscillatory model, will be tested if advisable. 
3. 
The PKPD model will be build using the individual PK parameter estimates and individual 
growth model parameter estimates as regression parameters. Estimation of typical and 
individual PD parameters will first be performed with IQRtools SysFit to investigate model 
identifiability and second with Monolix to additionally estimate IIV.  
 
Estimations will be done using gradient-based SysFit algorithm in IQRtools or SAEM algorithm 
in Monolix. Other appropriate methods may be used if advisable. 
 


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Inter-individual variability (IIV) is implemented for normally distributed parameters using the 
following equation with 𝛩0 as population average parameter, 𝛩𝑖 as individual parameter, and 
𝜂𝑖 as random effect that is distributed normally around zero (𝜂𝑖∼𝑁(0, 𝜔2)). 
𝛩𝑖= 𝛩0 + 𝜂𝑖 
The following equation is used for log-normally distributed parameters. 
ln(𝛩𝑖) = ln(𝛩0) + 𝜂𝑖 
Continuous covariates on log-normally distributed parameters will be implemented as follows. 
𝛩𝑖= 𝛩0 ⋅
𝐶𝑂𝑉𝑖
𝐶𝑂𝑉𝑚𝑒𝑑𝑖𝑎𝑛
𝛽
⋅𝜂𝑖 
𝛩𝑖 represents the individual parameter, 𝛩0 the population mean value, 𝐶𝑂𝑉𝑖 the individual 
covariate value, 𝐶𝑂𝑉𝑚𝑒𝑑𝑖𝑎𝑛, the population median covariate value, 𝛽 the covariate coefficient, 
and 𝜂𝑖 the individual random effect. 
Categorical covariates on log-normally distributed parameters will be implemented as follows. 
𝛩𝑖= 𝛩0 ⋅𝛴𝑗(𝑒𝛽𝑗⋅𝐶𝑂𝑉𝑖𝑗) ⋅𝜂𝑖 
The individual covariate values 𝐶𝑂𝑉𝑖𝑗 are 1 if subject i belongs to the jth category of the 
covatiate and 0 otherwise. 𝑏𝑒𝑡𝑎𝑗 is the covariate value for the jth category. For one category, 
i.e. the reference, 𝑏𝑒𝑡𝑎𝑗 is 0. 
 
For the NLME modeling with Monolix, the log-likelihood and the Fisher information matrix will 
be approximated by linearization. The number of iterations in the burn-in and the accumulation 
phase will be 500 and 200 respectively, but might be adjusted if required based on inspection 
of parameter estimate and objective function traces along estimation iterations. Individual 
parameters will be determined as conditional modes. 
For PD modelling with IQRtools SysFit implementation a non-linear fixed-effects modelling 
approach is employed. Typical and individual parameters are both treated as fixed effects. The 
parameterization of individual parameters and covariates is fully consistent with the NLME 
parameterization above. The variances 𝜔2 of NLME random effects are accounted for by 
quadratic priors,  
 
 
added to the log-likelihood function, where the values for 𝜔2 are fixed and the 𝜂 parameters 
are estimated. The profile-likelihood method [RAU09, KAS19] is used to compute confidence 
intervals of the parameters estimated with the SysFit approach. 
 Model evaluation 
Assessment of model adequacy and decisions about increasing model complexity will be driven 
by the data and guided by goodness-of-fit criteria, including 
1. 
visual inspection of diagnostic scatter plots (observed vs. predicted concentration, 
residual/weighted residual vs. predicted concentration or time and histograms of individual 
random effects, for example), 
2. 
successful convergence of the minimization routine with at least 2 significant digits in 
parameter estimates, 
3. 
plausibility of parameter estimates, 
4. 
precision of parameter estimates, 
5. 
correlation between model parameter estimation errors<0.95, and 
6. 
the Bayesian information criterion (BIC), given the minimum objective function value and 
number of estimated parameters. 
For the nonlinear fixed effects models, additional diagnostic plots will be produced: 
7. 
objective function values across multiple fits from randomised initial guesses, and 
8. 
profile likelihood plots 
 


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All parameter estimates will be reported with a measure of estimation uncertainty, such as the 
relative standard error of the estimates. The individual PK fits will be used to evaluate the 
adequacy to use the individual PK parameter estimates as regression parameters for PD 
modeling. 
 
The adequacy of simulation with the selected models will be evaluated by visual predictive 
checks (VPCs). VPCs for each dose level will be performed by simulation of the study 200 
times taking parameter estimation uncertainty into account. 95%-confidence intervals for the 
5th percentile, the median, and the 95th percentile will be derived and compared to the 
corresponding values based on the data. 
11.4.2 Building a PK model 
The PK of MMV533 will be modeled using compartmental models describing the absorption 
after oral administration, distribution between central and peripheral compartments, and the 
elimination from the central compartment. The visual data analysis will guide the selection of 
models that will be tested (e.g., with respect to number of compartments, linear or saturable 
elimination, absorption kinetics and error model). Covariates will be included if appropriate. 
Estimations will be done using SAEM algorithm in Monolix. Other appropriate methods may be 
used if advisable. 
 
FIH data from MMV_MMV533_19_01  has previously indicated that MMV533 PK is adequately 
described by a two-compartment model with zero order absorption parameterized in terms of  
CL, Vc, Q1, Vp1 and TK0. Therefore, this structural model will initially be used to model 
MMV533 PK using the PK modeling dataset. If required to adequately describe MMV533  PK, 
structural models with greater numbers of compartments and different absorption models (eg 
first-order rate, lag) will be fitted.  
 
An exploratory investigation of covariate-parameter relationships will be undertaken during the 
PK modelling step. The covariate WT0 on the clearance and volume parameters will be 
included to allow predictions in children. Since the body weight distribution may be narrow, the 
exponents will be fixed to 0.75 and 1 respectively on clearances and volumes of distribution. 
Other covariates of interest may include AGE, SEX, Infection status and PLbase – however, 
depending on the population make-up of these covariates, some may not be included. In the 
event that the distributions of WT0 and AGE are very narrow, a reference value for the 
population may be used instead of individual volunteer covariates.  
 
Covariate modeling will be undertaken in the following steps:  
• 
Pre-defined covariate-parameter relationships will be identified based on exploratory 
analysis and mechanistic plausibility – in particular, WT0 on clearance and volume PK 
parameters (central and peripheral compartments, if appropriate).  
• 
A full model will be constructed, avoiding simultaneous inclusion of covariates with 
correlation coefficients >0.5.  
• 
Population parameters will be estimated (both fixed effects [covariate coefficients and 
structural model parameters] and random effects).  
• 
An exploratory assessment of any remaining trends will be conducted by graphical 
inspection of all covariate effects (plots of MAP Bayes estimates of individual random 
effects and/or WRES from the full model vs. covariates).  
• 
Inferences about clinical relevance of parameters will be based on the resulting 
parameter estimates of the full model and measures of estimation precision (asymptotic 
standard errors, bootstrap 95% confidence intervals or log-likelihood profile).  
• 
No hypothesis testing will be conducted.  


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• 
This approach enables the direct assessment of clinical relevance of covariate effects 
and also provides some explanation for the apparent absence of a covariate effect (true 
lack of an effect vs. lack of information about that effect). 
Based on diagnostics plot (if shrinkage is not too high (>30%)) the estimation of random effect 
covariance matrix will be considered. Additionally, it will be attempted to estimate the full 
random effect covariance matrix. In order to assess the identifiability of the correlations 
between random effects, parameter estimations will be repeated from randomly chosen initial 
guesses for the fixed effect parameters that are estimated. All resulting parameters, including 
the correlation estimates for the random effects will be compared.  
11.4.3 Building a PKPD model 
PD model development will be done using gradient based algorithms in IQRTools SysFit. The 
selected model will then be estimated with SAEM in Monolix to allow for estimation of IIV. 
Other appropriate methods may be used if advisable. As a general concept the changes in 
living parasite 𝑃 are modeled as the effect of a net exponential growth rate 𝐺𝑅 and a killing or 
clearance rate 𝐾𝑖𝑙𝑙 due to MMV533. The initial parasitemia 𝑃𝑏𝑎𝑠𝑒 at time 𝑡0 will be derived 
from the mean parasitemia which was observed at treatment administration and a parameter 
𝑃𝐿𝑒𝑟𝑟 to allow for population and individual deviations. The equations are expressed in the 
log-scale such as: 
𝑑𝑃𝐿
𝑑𝑡
=
𝐺𝑅−𝐾𝑖𝑙𝑙
𝑃𝐿(𝑡0)
=
𝑃𝐿𝑏𝑎𝑠𝑒+ 𝑃𝐿𝑒𝑟𝑟
 
 
where 𝑃𝐿= ln(𝑃) is the log-transformed parasite counts. 
  
Three different models describing the relationship of MMV533 plasma concentration on the 
killing rate will be tested. 
11.4.4 Simulations in patients 
Simulations will be performed using the final PKPD model from this analysis.  
 
Simulations will be performed for single dose regimen of a range of MMV533 doses from 20mg 
to the maximum feasible dose. For each dose level, 200 trials with 625 subjects will be 
performed. Dose levels, number of trials and number of subjects may be adjusted if advisable. 
For each trial a new set of population parameters will be sampled from the uncertainty 
distribution and individual parameters will be sampled from the IIV. The covariates age, body 
weight and baseline parasitemia will be sampled from a clinical dataset of real patients, 
specifically an established dataset of African Children patients. 
 
The baseline parasitemia in patients are typically 1000 fold higher than in challenge volunteers 
and in the range of 104 p/uL 
 PKPD endpoints 
• 
PKPD equations comprising the final structural model  
• 
Primary PK and PD parameters: estimated values with 90% confidence interval 
• 
Secondary PD parameters from simulations in volunteers: APR28Csoff and 
APR28Cson (value and 90% confidence interval), parasite clearance time (median and 
90% confidence interval) as a function of MMV533 dose. 
 
The following parameters will be calculated (median and 95%CI): 
• 
Cmax: maximum MMV533 plasma concentration 


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• 
AUC: Area under the MMV533 plasma concentration curve 
• 
PRR48: Parasite reduction ratio after 48h 
• 
Parasite clearance time: time to reach the microscopic LOD (10 p/uL) 
• 
ETF CSoff: Early treatment failure clinical symptoms off; Parasitemia on day 2 higher 
than on day 0, irrespective of axillary temperature, or, parasitemia on day 3, or, 
parasitemia on day 3 >= 25% of cound on day 0. 
• 
ETF CSon: Early treatment failure clinical symptoms on; Parasitemia on day 2 higher 
than on day 0, irrespective of axillary temperature, or, parasitemia on day 3 >= 25% of 
cound on day 0. 
• 
LCF28: Late clinical failure at day 28: Parasitemia above LLOQ on any day between 
day 4 and day 28 in volunteers who did not previously meet any of the criteria of ETC 
CSon. 
• 
LPF28 CSoff: Late parasitological failure at day 28 clinical symptoms off: Parasitemia 
above LLOQ on any day between day 7 and day 28 with axillary temperature < 37.5°C 
in volunteers who did not previously meet any of the criteria of ETF CSoff. 
• 
LPF28 CSon: Late parasitological failure at day 28 clinical symptoms on: Parasitemia 
above LLOQ on any day between day 7 and day 28 with axillary temperature < 37.5°C 
in volunteers who did not previously meet any of the criteria of ETF CSon or LCF28. 
• 
APR28 CSoff: Adequate parasitological response at day 28 clinical symptoms off; 
Absence of parasitemia on day 28 irrespective of axillary temperature, in volunteers 
who did not previously meet any of the criteria of ETF CSoff or LPF28 CSoff. 
• 
APR28 CSon: Adequate parasitological response at day 28 clinical symptoms on; 
Absence of parasitemia on day 28 irrespective of axillary temperature, in volunteers 
who did not previously meet any of the criteria of ETF CSon or LCF28 or LPF28 CSon. 
 
The following secondary efficacy parameters will also be calculated:  
 
The minimum inhibitory concentration (MIC), the minimal parasiticidal concentration (MPC90), 
and the parasite reduction rate in 48 h (PRR48) are derived from the PD models. The MIC is 
defined as the concentration when parasite clearance by the drug equals the parasite growth, 
i.e., the drug concentration at the time at which the minimum parasite concentration is 
observed. It is calculated with the following equation in case of the Emax model. 
𝑀𝐼𝐶= 𝐸𝐶50 (
𝐺𝑅
𝐸𝑚𝑎𝑥+ 𝐺𝑅)
1/𝐻𝑖𝑙𝑙
 
For the other models, the calculation is only valid at steady-state. However, an apparent MIC 
is determined by simulations as the concentration 𝐶𝑐 at the time when the predicted parasite 
counts are at the minimum. 
The MPC90 is defined as the concentration at which the clearance effect is at 90% of the 
maximum. It is calculated as follows for the Emax model. 
𝑀𝑃𝐶90 = 𝐸𝐶50 ⋅91/𝐻𝑖𝑙𝑙 
For the other models, the calculation is only valid at steady-state. However, an apparent 
MPC90 is determined by simulations as the blood concentration 𝐶𝑐 at the time when the 
predicted clearance effect is at 90% of the maximum during the drug elimination phase. 
The PRR48 is defines as the parasite clearance achieved within 48 hours, usually given as the 
reduction of values on log10 transformed scale. The maximum capacity of parasite clearance 
in 48 hours is determined as follows assuming that concentrations are maintained well above 
the MPC90 for this time span. 
𝑃𝑅𝑅48 = 48ℎ𝐸𝑚𝑎𝑥−𝐺𝑅
ln(10)
 
 


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 Software 
All data processing, analysis, model setup and modeling result analysis including goodness-
of-fit plots will be performed in R 3.6.3 and IQRtools package 1.8.0 or above. 
NLME modelling will be performed with Monolix 2019R1 using Stochastic Approximation 
Expectation Maximization (SAEM) for parameter estimation. For PD modelling where typically 
the variance of random-effects cannot be estimated from the data, the IQRtools SysFit 
approach will be used to estimate typical and individual PD parameters. 
All analyses will be done in a working directory containing all data files, scripts, and outputs of 
the analysis. A library of functions related to the analysis of PKPD studies of anti-malarials may 
be used that is available at https://github.com/MedicinesForMalariaVenture/MMVmalaria. 
 
 
 
 


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12. SAFETY  
Safety and tolerability will be assessed by clinical review of the following parameters:  
• AEs (including SAEs and AESIs) 
• Vital signs  
• 12-lead ECG 
• Haematology, chemistry, urinalysis 
• Physical examination 
• Malaria clinical score 
All descriptive statistics for most safety parameters will be evaluated using the Safety Set 
except AEs where AE will be evaluated using the FAS and Safety Set. 
 Adverse Events 
Analysis Set: FAS/Safety Set 
12.1.1 Definition of variables 
• Inoculum Emergent Adverse Event (IEAE) 
o An IEAE is defined as an AE that commences on, or after, the administration of 
the challenge agent for the inoculation up to the end-of-study (EOS) visit 
(inclusive). AEs without an onset date or time will be defined as inoculum 
emergent except if an incomplete date (e.g., month and year) clearly indicates 
that the event started prior to the administration of the inoculation challenge 
agent, or if the AE stop date indicates that the event stopped prior to the  
administration of the inoculation challenge agent. Evaluation on IEAE will be 
based on the FAS. 
• Treatment Emergent Adverse Event (TEAE) 
o A TEAE is defined as an AE that commences on, or after, the first administration 
of IMP up to the end-of-study (EOS) visit (inclusive). AEs without an onset date 
or time will be defined as treatment emergent except if an incomplete date (e.g., 
month and year) clearly indicates that the event started prior to first 
administration of IMP, or if the AE stop date indicates that the event stopped 
prior to the first administration of IMP. Evaluation on TEAE will be based on the 
Safety Set. 
• Adverse Events of Special Interest (AESI) 
o Adverse Events of Special Interest (AESIs) may be serious or non-serious and 
are defined by the Sponsor as being of specific scientific and/or medical concern 
to the Sponsor’s product or program. Evaluation on AESI will be based on both 
Safety Set and FAS depending on if it is treatment emergent or inoculum 
emergent adverse events. 
12.1.2 Parameters 
• Event Term 
• Dates and times of onset and resolution 
• Severity (CTCAE Grades 1 to 5) 
• Outcome (Not Recovered / Not Resolved; Recovered / Resolved; Recovered / Resolved 
with Sequelae; Recovering / Resolving; Fatal; Unknown) 
• Relationship of AE to Investigational medicinal product (Not Related, Related) 
• Relationship of AE to rescue medication (Not Related, Related) 
• Relationship of AE to malaria challenge agent (Not Related, Related) 
• Relationship of AE to study procedures (Not Related, Related) 
• Action taken with Investigational medicinal product (No action taken; Rescue medication 
administered instead of IMP; Not applicable) 


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• Other actions taken (including withdrawal from the study) 
• Seriousness (and Serious Adverse Event (SAE) criteria) 
• AESI status (Yes/No) 
• Relatedness to COVID-19 (Yes/No) 
Derived parameters: 
• Duration in hours  
• Time in days of onset relative to first IMP administration 
12.1.3 Biostatistical methods 
Safety analyses will also be done specifically for AEs that commence during the inoculation 
period, defined as the time from the inoculum injection (Day-8) to the day before the IMP 
administration (Day -1) visit (included). AEs with partial start dates will be considered as not 
having commenced during the inoculation period.  
 
Adverse events (AE) will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) version 24.1 – Sep 2021 and grouped by system organ class (SOC) and preferred 
terms (PT).  Their severity will be graded according to NCI-CTCAE v5.0 27 Nov 2017.  
 Listings 
All AE data will be listed for each volunteer, including severity, relationship to IMP, relationship 
to study procedures, relationship to rescue mediation, relationship to malaria challenge agent, 
outcome and actions taken. In addition, listings of AEs leading to discontinuation of the study, 
SAEs and deaths, will be provided as applicable. 
 Tables 
The main AE summaries will be restricted to Inoculum Emergent Adverse events (IEAE) and 
Treatment Emergent Adverse Events (TEAEs).  
 
All reported IEAEs/TEAEs, including SAEs and AESIs, will be mapped to standard MedDRA 
coding terms and grouped by SOC and PT.   
 
An overview summary table of AEs will be provided by cohort and overall including: 
• 
Number of events and number of volunteers reporting at least one of the following: 
o IEAE/TEAE 
o Serious IEAE/TEAE 
o Malaria Challenge Agent Related IEAEs 
o IMP Related TEAE  
o IMP Related Serious IEAE/TEAE  
• 
Number of volunteers with at least one IEAE/TEAE by maximum severity 
• 
Number of IEAE/TEAE by relationship to IMP 
• 
Number of IEAE/TEAE by relationship to rescue medications 
• 
Number of volunteers withdrawn from the study due to a IEAE/TEAE  
• 
Number of IEAE during inoculation period by relationship to the malaria challenge agent 
• 
Number of deaths 
 
A duplicate overview summary table will also be presented specifically for the AESIs. 
 
The number of events, as well as the number and percentage of volunteers experiencing an 
IEAE/TEAE, will be summarised for each SOC and PT by treatment arm and overall for the 
following categories of events: 
• 
All IEAEs/TEAEs 
• 
IEAEs/TEAEs by severity 


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• 
Malaria challenge agent related IEAEs 
• 
IMP related TEAEs  
• 
Malaria challenge agent related IEAEs by severity 
• 
IMP related TEAEs by severity 
• 
Inoculum/Treatment Emergent SAEs 
• 
IEAEs/TEAEs leading to study withdrawal 
• 
IEAEs/TEAEs of Special Interest (AESIs) 
For the summaries of TEAEs, volunteers who experience the same AE (in terms of the 
MedDRA preferred term) more than once will only be counted once. 
 


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 Concomitant Medication 
Medications used in this study will be coded using WHODrug Global version B3 Sep 2021 – 
Added Context. 
 
Concomitant medications are defined as medications continued or newly received at or after 
administration of IMP, through to the End of Study visit. 
 
If a medication has a missing or partial missing start/end date or time and it cannot be 
determined whether it was taken before initial treatment or concomitantly, it will be considered 
as prior and concomitant. 
 
Concomitant medications will be summarised by ATC and PN. The summary tables will show 
the number and percentage of volunteers taking each medication by ATC and PN. 
 
For the summaries of prior and concomitant medications, volunteers who take the same 
medication (in terms of the ATC and PN) more than once will only be counted once for that 
medication. 
 
Use of rescue medications will be analysed as part of the treatment exposure analysis (Section 
8.1).  
 
 
 


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 Laboratory 
12.3.1 Parameters 
 Haematology
• 
Basophils (absolute) 
• 
Monocytes (absolute) 
• 
Eosinophils (absolute) 
• 
Neutrophils (absolute) 
• 
Haematocrit 
• 
Platelet count 
• 
Haemoglobin 
• 
Red blood cell count 
• 
Lymphocytes (absolute) 
• 
White blood cell count 
 Biochemistry 
• 
Alanine Aminotransferase (ALT) 
• 
Gamma Glutamyl Transpeptidase 
(GGT) 
• 
Albumin 
• 
Glucose (random and fasting) 
• 
Alkaline phosphatase (ALP) 
• 
Glucose-6-phosphatase (G6PD) 
• 
Aspartate Aminotransferase (AST) 
• 
Lactate dehydrogenase (LDH) 
• 
Bicarbonate 
• 
LDL 
• 
HDL 
• 
Bilirubin (direct) 
• 
Phosphate 
• 
Bilirubin (total) 
• 
Potassium 
• 
Calcium 
• 
Protein Total 
• 
Calculated eGFR (CKD-EPI) 
• 
Sodium 
• 
C-Reactive protein  
• 
Triglyceride 
• 
Chloride 
• 
Troponin T/high sensitivity 
• 
Cholesterol Total 
• 
Urea 
• 
Creatinine 
• 
Uric Acid 
• 
Creatine kinase 
 
 
Pregnancy Test and FSH 
 
• β-Human Chorionic Gonadotropin (β-HCG) (women of child bearing potential only) 
• Follicular Stimulating Hormone (FSH) (post-menopausal women only) 
 Urinalysis  
Dipstick Testing 
Quantitative Assessments 
Urine Chemistry 
• Red blood cells  
• Red blood cells 
• Glucose 
• Glucose 
• White blood cells 
• Protein 
• Ketone  
 
 
• White blood cells 
 
 
• Protein  
 
 
• pH  
 
 
 
 
 
Pregnancy Test 
 
• β-Human Chorionic Gonadotropin (β-HCG) (women of child bearing potential 
only) 
 Coagulation 
• 
International Normalized Ratio (INR) • 
Activated Partial Thromboplastin 
Time (APTT) 


Protocol Number: MMV_MMV533_20_01 
 
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 Serology 
• 
Hepatitis B surface antigen (HB 
sAG) 
• 
Anti-hepatitis B core antibodies 
(anti-HBc Ab) 
• 
Hepatitis C antibodies 
• 
Red blood cell antibodies 
• 
Human Immunodefiniciency Virus 
(HIV) Ag/Ab 1/2 (anti-HIV1 and 
anti-HIV2 Ab) 
12.3.2 Biostatistical methods 
 Listings 
All laboratory parameters and change from baseline values will be presented in data listings. 
Values outside the laboratory reference range will be listed with flags if considered low or high 
(where applicable) and if considered to be clinically significant by the investigator. 
 
Pregnancy test data will be listed only, for all women of child bearing potential (WOCBP). FSH 
data will be listed only, for all post-menopausal women.  
 
Coagulation data as well as qualitative and quantitative urinalysis data will be listed only. 
 Tables 
Haematology, biochemistry and continuous dipstick urinalysis laboratory data will be 
summarised for each scheduled visit, including observed values, absolute change from each 
baseline.  
 
Categorical dipstick urinalysis results will be summarised for each scheduled visit using 
frequency tabulations.  
 
Laboratory abnormalities will be presented as cross-tabulations of the abnormality at each post-
baseline analysis visit versus the baseline abnormality. Numbers of subjects with treatment-
emergent abnormalities will also be shown. 
 
In addition, the liver function tests, namely AST, ALT, and total bilirubin, are used to assess 
possible drug-induced liver toxicity. The proportion of volunteers with Potential Clinically 
Significant Abnormality (PCSA) values at any postbaseline visit will summarized. The highest 
value of PCSA and time to the highest PCSA reading during inoculation period and since IMP 
administration will also be summarized. Any of the following event will be considered as a 
PCSA: 
 
• 
ALT: >3 x Upper Limit of Normal (ULN); >5 x ULN; >8 x ULN  
• 
AST: >3 x Upper Limit of Normal (ULN); >5 x ULN; >8 x ULN  
• 
ALT or AST >3 x ULN;  
• 
Total bilirubin >2 x ULN;  
• 
ALT or AST >3 x ULN and total bilirubin >2 x ULN at the same time point, together with a 
conjugated bilirubin fraction (direct bilirubin / total bilirubin) > 35% (Potential Hy’s law 
cases). 
 Vital Signs 
12.4.1 Parameters 
• 
Systolic Blood Pressure (SBP) (mmHg) 
• 
Diastolic Blood Pressure (DBP) (mmHg) 
• 
Heart Rate (beats/minute) 


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• 
Temperature (°C) 
12.4.2 Biostatistical methods 
All vital signs data will be listed for all volunteers.  Any values outside of the protocol defined 
inclusionary/exclusionary ranges (Table 4) will be flagged, with clinical significance status 
presented for out of range results. 
 
Table 4: Vital Signs Normal Ranges 
Parameter 
Range 
Systolic blood pressure             
90-140 mmHg 
Diastolic blood pressure           
40-90 mmHg 
Heart rate                                 
40-100 bpm 
Temperature   
>37.5°C a.m. 
>37.7°C p.m. 
 
Vital sign parameters will be summarised by presenting summary statistics for observed values 
and change from baseline values for each scheduled visit. 
 Body Measurements 
12.5.1 Definition of variables 
• 
Height (Screening Only) 
• 
Weight 
• 
Body mass index (BMI) 
12.5.2 Biostatistical methods 
Body measurement data will be listed for all volunteers and visits including height, weight and 
Body Mass Index (BMI) which is auto-calculated within the CRF.  
 
Observed values, as well as changes from each baseline, will be summarised descriptively for 
weight and BMI by visit. 
 Physical Examination 
12.6.1 Parameters 
• 
General appearance 
• 
Skin 
• 
HEENT (Head, Eyes, Ears, Nose, Throat) • 
Neurological/Reflexes 
• 
Lymphatic 
• 
Cardiovascular 
• 
Respiratory 
• 
Musculoskeletal 
12.6.2 Biostatistical methods 
Physical examination findings will be listed for all volunteers and visits 
 12-lead ECG 
12.7.1 Parameters 
• 
RR interval (msec) 
• 
Heart rate (beats/minute) 
• 
PR interval (msec) 
• 
QRS interval (msec) 


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• 
QT interval (msec) 
• 
QTc interval (msec) 
• 
QTcB interval (msec) 
• 
QTcF interval (msec) 
• 
Overall ECG assessment (Normal, Abnormal) 
• 
ECG abnormality (as appropriate) 
• 
Clinical Significance 
12.7.2 Biostatistical methods 
ECG parameters will be listed for all volunteers and visits. Triplicate ECGs will be presented in 
listings for individual readings as well as the mean for each triplicate. The triplicate means will 
be used for the summary table. Any value outside of the reference range (Table 5) will be 
flagged. 
 
Table 5: ECG Reference Range 
Parameter 
Range 
PR interval 
≤ 220 msec 
QRS interval 
50-120 msec 
QTcB/QTcF 
≤ 450 msec 
 
Observed values, as well as changes from each baseline, will be summarised descriptively for 
all ECG parameters by visit. An additional table will present the frequencies of volunteers who 
fulfill the following criteria at least once, considering all scheduled and non-scheduled visit data: 
• 
QTcF prolongation >30 msec 
• 
QTcB prolongation >30 msec 
• 
QTcF prolongation >60 msec 
• 
QTcB prolongation >60 msec 
• 
QTcF >450 msec 
• 
QTcB >450 msec 
• 
QTcF >480 msec 
• 
QTcB >480 msec  
 Malaria Clinical Score 
Malaria clinical score data will be listed for all volunteers, including the individual scores for 
each of the 14 signs/symptoms as well as the total score. The total of all the scores obtained 
on the 14 symptoms will also be presented, per timepoint. 
 
The number (and percentage) of volunteers scoring each symptom (0=absent; 1=mild; 
2=moderate; 3=severe) will be tabulated per treatment and per protocol defined timepoint. In 
addition, the total malaria clinical score will be treated as a continuous outcome and 
summarised per treatment and over timepoint, as well as a change from baseline, using 
descriptive statistics.  
 
The highest score as well as the time to the highest score observed will be tabulated and 
summarized using descriptive statistics. 
 Software 
SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA) will be used to analyze 
all Safety related statistical analysis. 


Protocol Number: MMV_MMV533_20_01 
 
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13. EXPLORATORY PARAMETERS 
Analysis Set: PD 
 Parameters 
• 
in vitro drug sensitivity testing to determine the 50% inhibitory concentrations (IC50) 
and the percentage surviving parasites, if recrudescence occurs 
• 
Presence or absence of gametocytaemia following a single dose of MMV533  
 Biostatistical methods 
Please refer to Section 10.6  for the detail of analysis method. 
 Software 
Data manipulation and data analyses for all pharmacodynamic data to be analyzed by QIMR 
will be performed using R (version 4.1.0 or higher). 
14. CHANGES TO THE PLANNED ANALYSIS 
Any deviation will be documented in the clinical study report. 
15. INTERIM AND FINAL ANALYSIS 
This trial has no formal interim analysis. 
16. REFERENCES 
1) MMV_MMV533_20_01Clinical Study Protocol, v3.0, 17 February 2022 
2) Wang CYT, Ballard EL, Pava Z Marquart L, Gaydon J, Murphy SC, Whiley D, O’Rourke 
P, McCarthy JS (2021) Analytical validation of a real-time hydrolysis probe PCR assay 
for quantifying Plasmodium falciparum parasites in experimentally infected human 
adults, Malaria Journal, 20(181). 
3) Marquart L, Baker M, O’Rourke P, McCarthy JS (2015) Evaluating the 
pharmacodynamic effect of antimalarial drugs in clinical trials by quantitative PCR, 
Antimicrobrial Agents and Chemotherapy,59, 4249–5 
 
 
 


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APPENDIX 
 
Planned listings 
 
Planned summary tables 
 
Planned summary figures 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 1 of 55 
 
MMV_MMV533_20_01: Mock Tables: Table of Contents 
Table XX - Analysis Populations ....................................................................................................................................................................................................................................... 4 
Table XX - Study Volunteer and Disposition ................................................................................................................................................................................................................... 5 
Table XX - Demographics and Baseline Characteristics ............................................................................................................................................................................................... 6 
Table XX - Summary of Prior Medications ....................................................................................................................................................................................................................... 8 
Table XX - Protocol Deviations .......................................................................................................................................................................................................................................... 9 
Table XX - IMP Administration......................................................................................................................................................................................................................................... 10 
Table XX – Summary of Pharmacokinetic Concentration ........................................................................................................................................................................................... 11 
Table XX – Summary of Pharmacokinetic Parameters ................................................................................................................................................................................................ 12 
Table XX – Parasitaemia Level: At IMP Dosing and Peak .......................................................................................................................................................................................... 13 
Table XX - Overall Summary of Inoculum Emergent Adverse Events ...................................................................................................................................................................... 14 
Table XX - Overall Summary of Treatment Emergent Adverse Events..................................................................................................................................................................... 15 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class and Preferred Term ........................................................................................................... 16 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class and Preferred Term ......................................................................................................... 17 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity ........................................................................................... 18 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity ......................................................................................... 19 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Relatedness to Malaria Challenge Agent .................................. 20 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Relatedness to IMP .................................................................... 21 
Table XX – Malaria Challenge Agent Related Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity .............................. 22 
Table XX – IMP Related Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity ................................................................. 23 
Table XX - Inoculum Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term ............................................................................................. 24 
Table XX - Treatment Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term ........................................................................................... 25 
Table XX - Inoculum Emergent Adverse Events Leading to Study Discontinuation by MedDRA System Organ Class and Preferred Term ................................................ 26 
Table XX - Treatment Emergent Adverse Events Leading to Study Discontinuation by MedDRA System Organ Class and Preferred Term .............................................. 27 
Table XX - Overall Summary of Inoculum Emergent Adverse Events of Special Interest (AESI) ......................................................................................................................... 28 
Table XX - Overall Summary of Treatment Emergent Adverse Events of Special Interest (AESI) ....................................................................................................................... 30 
Table XX - Inoculum Emergent Adverse Events of Special Interest (AESI) by MedDRA System Organ Class and Preferred Term .............................................................. 31 
Table XX - Treatment Emergent Adverse Events of Special Interest (AESI) by MedDRA System Organ Class and Preferred Term............................................................ 32 
Table XX - Summary of Concomitant Medications ....................................................................................................................................................................................................... 33 
Table XX - Haematology Results and Change from Baseline .................................................................................................................................................................................... 34 
Table XX - Cross-Tabulation of Haematology Abnormalities Versus Baseline ........................................................................................................................................................ 35 
Table XX - Biochemistry Results and Change from Baseline ..................................................................................................................................................................................... 36 
Table XX - Cross-Tabulation of Biochemistry Abnormalities Versus Baseline ......................................................................................................................................................... 37 
Table XX – Liver Function: Summary of Volunteers Potentially Clinically Significant Abnormality During Inoculation Period ......................................................................... 38 
Table XX – Liver Function: Summary of Volunteers Potentially Clinically Significant Abnormality Post IMP Administration ............................................................................ 39 
Table XX - Liver Function: Summary of Peak Readings During Inoculation Period ................................................................................................................................................ 40 
Table XX - Liver Function: Summary of Peak Readings Since IMP Administration ................................................................................................................................................ 41 
Table XX - Liver Function: Summary of Time to Peak Readings Since IMP Administration in Days During Inoculation Period ...................................................................... 42 
Table XX - Liver Function: Summary of Time to Peak Readings Since IMP Administration in Days ................................................................................................................... 43 
Table XX - Urinalysis (Continuous) Results and Change from Baseline................................................................................................................................................................... 44 
Table XX - Urinalysis (Categorical) Results .................................................................................................................................................................................................................. 45 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 2 of 55 
 
Table XX - Vital Signs Results and Change from Baseline ......................................................................................................................................................................................... 46 
Table XX - Abnormal Vital Signs Results ....................................................................................................................................................................................................................... 47 
Table XX – Body Measures ............................................................................................................................................................................................................................................. 48 
Table XX - ECG Results and Change from Baseline ................................................................................................................................................................................................... 49 
Table XX - ECG QTc Categorical Analyses .................................................................................................................................................................................................................. 50 
Table XX - ECG Clinical Assessment ............................................................................................................................................................................................................................. 51 
Table XX - Malaria Clinical Score Summary by Question ........................................................................................................................................................................................... 52 
Table XX – Malaria Clinical Total Score Results and Change from Baseline .......................................................................................................................................................... 53 
Table XX – Peak Total Malaria Clinical Score and Time to Peak Total Malaria Clinical Score by Subject.......................................................................................................... 54 
Table XX – Summary Peak Total Malaria Clinical Score and Time to Peak Total Malaria Clinical Score ........................................................................................................... 55 
 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 3 of 55 
 
Notes: 
• 
For summary table, the column header in each table will be displayed as below: 
• 
MMV 533 (20 mg) 
• 
MMV 533 (35 mg) 
• 
MMV 533 (100 mg) 
• 
MMV 533 (160 mg) 
• 
Overall 
• 
Column widths and text-wrapping may be altered in final output to best present the data. 
• 
Footnotes may be added/amended as required 
• 
Where a count is 0, the percentage will not be shown (e.g. 0(0.0%) will be displayed as 0). 
• 
Percentages will be rounded to one decimal place, with the denominator being the number of volunteers in the relevant population with non-missing data, 
unless otherwise specified. 
• 
If it is not possible to fit all groups on one page in some of the summary tables, the summary tables will be split across multiple pages. 
• 
If there is no data for a particular table (for example, SAEs, etc.), populate the table with “No Serious Treatment Emergent Adverse Events reported.”  
• 
Unscheduled visits and Early termination visits will be excluded from visit-based summary tables unless otherwise indicated 
• 
Refer to Statistical Deliverables document for output numbering 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 4 of 55 
 
Table XX - Analysis Populations 
Protocol: MMV_MMV533_20_01 
Population: All Screened Volunteers 
 
Dose Group 
Full Analysis Set 
N (%) 
Safety Set 
N (%) 
PK Analysis Set  
N (%) 
PD Analysis Set  
N (%) 
PK/PD Analysis Set 
N(%)* 
Inoculation Set 
N(%) 
 
 
 
 
 
 
 
MMV 533 (10 mg) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
MMV 533 (xx mg) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
MMV 533 (xx mg) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
MMV 533 (xx mg)  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
MMV 533 (xx mg) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
MMV 533 (200 mg) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Total 
X  
X  
X  
X  
X  
X  
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of volunteers in the relevant population set. 
* The PK/PD Analysis Set includes all volunteers from the PK set and all volunteers from the PD set from the VIS study only. 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 5 of 55 
 
Table XX - Study Volunteer and Disposition 
Protocol: MMV_MMV533_20_01 
Population: All Screened Set 
 
n(%) 
Treatment 
Treatment 
Treatment 
 
 
 
 
Signed Inform Consent 
X  
X  
X  
Received IMP 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Completed Study 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Early Withdrawal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
Primary Reason for Study Discontinuation 
 
 
 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Source: Listing X  
Percentages based on the number of volunteers in the Full Analysis Set. 
 
 
 
 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  If there are no early discontinuations, remove the “Primary Reason” section. 
If there is at least one early discontinuation, only include rows where there is at least one value > 0 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 6 of 55 
 
Table XX - Demographics and Baseline Characteristics 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
 
Statistic 
Treatment  
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
Age (years)* 
 
 
 
 
 
 
n 
X 
X 
X 
 
 
Mean 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
SD 
X.X 
X.X 
X.X 
 
 
Minimum 
X 
X 
X 
 
 
Maximum 
X 
X 
X 
 
 
 
 
 
 
Race 
 
 
 
 
 
White 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
………… 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Other 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
Sex n(%) 
 
 
 
 
 
Female 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Male 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Child-Bearing Potential 
 
 
 
 
 
Yes 
n (%)*** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
No 
n (%)*** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Post-menopausal 
 
 
 
 
 
Yes 
n (%)*** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
No 
n (%)*** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
* At Screening Visit 
** Percentages based on the number of volunteers in the relevant population with non-missing data 
*** Percentages based on the number of female volunteers in the relevant population with non-missing data 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 7 of 55 
 
Table XX - Demographics and Baseline Characteristics 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
 
Statistic 
Treatment  
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
Hispanic or Latino 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Not Hispanic or Latino 
n (%)** 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
Height (cm)* 
 
 
 
 
 
 
n 
X 
X 
X 
 
 
Mean 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
SD 
X.X 
X.X 
X.X 
 
 
Minimum 
X 
X 
X 
 
 
Maximum 
X 
X 
X 
 
 
 
 
 
 
Weight (kg)* 
 
 
 
 
 
 
n 
X 
X 
X 
 
 
Mean 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
SD 
X.X 
X.X 
X.X 
 
 
Minimum 
X 
X 
X 
 
 
Maximum 
X 
X 
X 
 
 
 
 
 
BMI (kg/m2)* 
 
 
 
 
 
 
n 
X 
X 
X 
 
 
Mean 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
SD 
X.X 
X.X 
X.X 
 
 
Minimum 
X 
X 
X 
 
 
Maximum 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
* At Screening Visit 
** Percentages based on the number of volunteers in the relevant population with non-missing data 
*** Percentages based on the number of female volunteers in the relevant population with non-missing data 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 8 of 55 
 
Table XX - Summary of Prior Medications 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Anatomical Therapeutic Chemical (ATC) Level 3 
               Preferred Name (PN) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
Number of volunteers reporting at least one prior medication 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
Number of prior medications reported 
X 
X 
X 
 
 
 
 
 
ATC1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
…. 
 
 
 
 
PNx 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
ATC2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
…. 
 
 
 
 
PNx 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
……….. 
 
 
 
Source: Listing X 
Medications were coded to preferred name and ATC class using WHO DD version 20YY:MM (ATC Class Level 3) 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 9 of 55 
 
Table XX - Protocol Deviations 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
Number of volunteers with at least one protocol deviation 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Number of protocol deviations* 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Number of volunteers with at least one minor protocol deviation 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Number of volunteers with at least one major protocol deviation 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
Number of protocol deviations 
X 
X 
X 
Number of minor protocol deviations 
X 
X 
X 
Number of major protocol deviations 
X 
X 
X 
 
 
 
 
Deviations by category  
 
 
 
XXXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
XXXXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of volunteers in the relevant population. 
*Percentages based on the total number of protocol deviations. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 10 of 55 
 
Table XX - IMP Administration 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Treatment 
(N=X) 
Treatment 
(N=X) 
 
 
IMP Total Dose (mg) 
       n 
X 
X 
       Mean 
X.X 
X.X 
       Median 
X.X 
X.X 
       SD 
X.X 
X.X 
       Minimum 
X 
X 
       Maximum  
X 
X 
 
 
Malaria Challenge Total Volume (mL) 
 
 
 
 
       n 
X 
X 
       Mean 
X.X 
X.X 
       Median 
X.X 
X.X 
       SD 
X.X 
X.X 
       Minimum 
X 
X 
       Maximum  
X 
X 
 
 
Rescue Medication Total Dose (mg) 
       n 
X 
X 
       Mean 
X.X 
X.X 
       Median 
X.X 
X.X 
       SD 
X.X 
X.X 
       Minimum 
X 
X 
       Maximum  
X 
X 
 
 
Source: Listing X 
SD: Standard Deviation 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 11 of 55 
 
Table XX – Summary of Pharmacokinetic Concentration 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set 
 
Matrix: Plasma 
 
Concentration (unit) 
Treatment 
Statistic 
Predose 
0.5 h 
1 h 
….. 
 
 
 
 
 
 
Treatment 
Geometric Mean 
X.X 
X.X 
X.X 
 
Geometric SD 
X.X 
X.X 
X.X 
 
 
Geometric CV 
X.X 
X.X 
X.X 
 
 
Arithmetic Mean 
X.X 
X.X 
X.X 
 
 
Arithmetic SD 
X.X 
X.X 
X.X 
 
 
Arithmetic CV 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
Minimum 
X.X 
X.X 
X.X 
 
 
Maximum 
X.X 
X.X 
X.X 
 
 
n 
X 
X 
X 
 
 
………… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation; CV: Coefficient of variation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Include plasma MMV533 and metabolites - MMV022 and MMV023. Start a new page with different matrix.  
Programming Note:  Include all scheduled PK samples. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 12 of 55 
 
Table XX – Summary of Pharmacokinetic Parameters 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set 
 
Matrix: Plasma 
Parameter 
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
 
Cmax (unit) 
Geometric Mean 
X.X 
X.X 
X.X 
 
 
Geometric SD 
X.X 
X.X 
X.X 
 
 
Geometric CV 
X.X 
X.X 
X.X 
 
 
Arithmetic Mean 
X.X 
X.X 
X.X 
 
 
Arithmetic SD 
X.X 
X.X 
X.X 
 
 
Arithmetic CV 
X.X 
X.X 
X.X 
 
 
Median 
X.X 
X.X 
X.X 
 
 
Minimum 
X.X 
X.X 
X.X 
 
 
Maximum 
X.X 
X.X 
X.X 
 
 
n 
X 
X 
X 
 
 
………… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation; CV: Coefficient of variation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Include plasma MMV533 and metabolites - MMV022 and MMV023. Start a new page with different matrix.  
Programming Note:  Include all PK parameters: Cmax,tmax, AUClast, AUC0-168, 
AUCinf, %AUCextrap, t1/2, Lambda-z, CL/F, Vz/F. 
Additional plasma ratios (metabolite to parent drug) of: Cmax, AUClast, AUCinf 
to be included on metabolites matrix.  
Please note: Tmax summary statistics will be provided as n, minimum, median, 
and maximum only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 13 of 55 
 
Table XX – Parasitaemia Level: At IMP Dosing and Peak   
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
Dose Group 
Volunteer 
Parasitaemia at IMP Dosing 
(Day 1) 
(geometric mean 
parasites/500 μL of packed 
RBCs) 
Peak Parasitaemia during 
Study (timepoint) 
(geometric  mean 
parasites/500 μL of packed 
RBCs) 
 
 
 
 
 
 
 
 
Treatment  
XXX 
XXX 
XXX (Day X) 
 
 
 
XXX 
XXX 
XXX (Day X) 
 
 
 
 
 
 
 
 
Treatment  
XXX 
XXX 
XXX (Day X) 
 
 
 
XXX 
XXX 
XXX (Day X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
: 
 
 
 
 
 
: 
 
 
 
 
 
: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing XX 
Days in the () is related to the day since the IMP is administered. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Start a new page with different PD parameters. Apply all relevant scheduled visits 
to the PD parameters. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 14 of 55 
 
Table XX - Overall Summary of Inoculum Emergent Adverse Events   
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one malaria challenge agent 
related IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one serious IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one malaria challenge agent 
related serious IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related 
serious IEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one IEAE by maximum severity 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 1: Mild 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 2: Moderate 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 3: Severe 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 4: Life-threatening 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 5: Fatal 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Number of volunteers with IEAEs by Relationship to rescue 
medication 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with IEAEs during inoculation period by 
relationship to the malaria challenge agent 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers withdrawn from the study due to a IEAE 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Number of deaths 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 15 of 55 
 
Table XX - Overall Summary of Treatment Emergent Adverse Events   
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one IMP-related TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one serious TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one IMP-related serious TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related 
serious TEAE 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one TEAE by maximum severity 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 1: Mild 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 2: Moderate 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 3: Severe 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 4: Life-threatening 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 5: Fatal 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Number of volunteers with TEAEs by Relationship to rescue 
medication 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers withdrawn from the study due to a TEAE 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Number of deaths 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 16 of 55 
 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 17 of 55 
 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 18 of 55 
 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity  
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
(N=X) 
 
Treatment  
(N=X) 
 
Treatment  
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 5: Fatal 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a maximum severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 19 of 55 
 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity  
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 5: Fatal 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest maximum for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 20 of 55 
 
Table XX - Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Relatedness to Malaria Challenge Agent  
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
PT2 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 21 of 55 
 
Table XX - Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Relatedness to IMP  
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
PT2 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Not Related 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 22 of 55 
 
Table XX – Malaria Challenge Agent Related Inoculum Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity  
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
(N=X) 
 
Treatment  
(N=X) 
 
Treatment  
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 5: Fatal 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A malaria challenge agent related inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria 
challenge agent and is related to malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a maximum severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 23 of 55 
 
Table XX – IMP Related Treatment Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity  
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
            Preferred Term (PT) 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
 
Treatment  
Group 
(N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 5: Fatal 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
PT1 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 1: Mild 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 2: Moderate 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 3: Severe 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
Grade 4: Life-threatening 
 
 
 
 
 
 
 
 
Grade 5: Fatal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An IMP related treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP and is related to IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest maximum for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 24 of 55 
 
Table XX - Inoculum Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 25 of 55 
 
Table XX - Treatment Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 26 of 55 
 
Table XX - Inoculum Emergent Adverse Events Leading to Study Discontinuation by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent . 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 27 of 55 
 
Table XX - Treatment Emergent Adverse Events Leading to Study Discontinuation by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 28 of 55 
 
Table XX - Overall Summary of Inoculum Emergent Adverse Events of Special Interest (AESI) 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one Inoculum-Emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one malaria challenge agent related Inoculum-Emergent 
AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related inoculum-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one serious inoculum-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one malaria challenge agent related serious inoculum-
emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related serious inoculum-emergent 
AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one inoculum-emergent AESI by maximum severity 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 1: Mild 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 2: Moderate 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 3: Severe 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 4: Life-threatening 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 5: Fatal 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Number of volunteers with inoculum-emergent AESI by Relationship to rescue medication 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with inoculum-emergent AESI during inoculation period by 
relationship to the malaria challenge agent 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers withdrawn from the study due to an inoculum-emergent AESI 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Number of deaths 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event of special interest is defined as an adverse event of special interest that occurred or worsened following administration of the malaria 
challenge agent.. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of AESIs column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 29 of 55 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 30 of 55 
 
Table XX - Overall Summary of Treatment Emergent Adverse Events of Special Interest (AESI) 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
Nr(%) of 
Volunteers 
Nr of 
AESIs 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one treatment-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one IMP-related treatment-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related treatment-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one serious treatment-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one IMP-related serious treatment-emergent AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Number of volunteers with at least one study procedure-related serious treatment-emergent 
AESI 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers with at least one treatment-emergent AESI by maximum severity 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 1: Mild 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 2: Moderate 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 3: Severe 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 4: Life-threatening 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Grade 5: Fatal 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Number of volunteers with treatment-emergent AESI by relationship to rescue medication 
 
 
 
 
 
 
 
 
Not Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
Related 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
Number of volunteers withdrawn from the study due to an treatment-emergent AESI 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
Number of deaths 
X (XX.X%) 
 
 X (XX.X%) 
 
 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event of special interest is defined as an adverse event of special interest that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of AESI column. 
If a participant has multiple occurrences of an AE by severity, the participant is presented only once in the Nr(%) column as a highest severity for a given SOC and preferred 
term. 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Page X of Y 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 31 of 55 
 
Table XX - Inoculum Emergent Adverse Events of Special Interest (AESI) by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
IEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
An inoculum-emergent adverse event (IEAE) is defined as an adverse event that occurred or worsened following administration of the malaria challenge agent. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of IEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 32 of 55 
 
Table XX - Treatment Emergent Adverse Events of Special Interest (AESI) by MedDRA System Organ Class and Preferred Term 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
 
Treatment  
 (N=X) 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
Nr(%) of 
Volunteers 
Nr of 
TEAEs 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
 
 
 
 
 
 
…. 
…. 
… 
 
…. 
… 
 
…. 
… 
 
PTx 
X (XX.X%) 
X 
 X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
Source: Listing X 
Adverse events were coded to System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following administration of the IMP. 
If a participant has multiple occurrences of an AE, the participant is presented only once in the Nr(%) column. Occurrences are counted each time in the Nr of TEAEs column. 
Percentages based on the number of volunteers in the relevant population 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 33 of 55 
 
Table XX - Summary of Concomitant Medications 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Anatomical Therapeutic Chemical (ATC) Level 3 
               Preferred Name (PN) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
Number of volunteers reporting at least one concomitant medication 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
Number of concomitant medications reported 
X 
X 
X 
 
 
 
 
 
ATC1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
…. 
 
 
 
 
PNx 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
ATC2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
PN2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
…. 
 
 
 
 
PNx 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
……….. 
 
 
 
Source: Listing X 
Medications were coded to preferred name and ATC class using WHO DD version 20YY:MM (ATC Class Level 3)  
Percentages based on the number of subjects in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 34 of 55 
 
Table XX - Haematology Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
Measured Values 
Change from Baseline 
Out of NR Count 
Dose Group 
Parameter (unit) 
Visit 
N Mean 
SD 
Median 
Min Max N Mean 
SD 
Median 
Min 
Max 
L 
N 
H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
X X.XX 
X.XX 
X.XX 
X.X X.X X X.XX 
X.XX X.XX 
X.X X.X 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X  
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
Percentages based on the number of subjects in the relevant population. 
NA = Not Applicable; SD = Standard Deviation; NR = Normal Ranges; L = Low; N = Normal; H = High. 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 35 of 55 
 
Table XX - Cross-Tabulation of Haematology Abnormalities Versus Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Dose Group 
Parameter (unit) 
Visit 
 
Baseline 
Low 
Normal 
High 
Missing 
Total 
 
 
 
 
 
 
 
 
Treatment (N=X) XXXXXXXX (xxx) 
XXXX 
Low 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
 
Normal 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
High 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
Missing 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
Total 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
Percentages based on the number of volunteers in the relevant population. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 36 of 55 
 
Table XX - Biochemistry Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
Measured Values 
Change from Baseline 
Out of NR Count 
Dose Group 
Parameter (unit) 
Visit 
N Mean 
SD 
Median 
Min Max N Mean 
SD 
Median 
Min 
Max 
L 
N 
H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) XXXXXXXX (xxx) 
XXXX 
X X.XX 
X.XX 
X.XX 
X.X X.X X X.XX 
X.XX X.XX 
X.X X.X 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
Percentages based on the number of subjects in the relevant population. 
NA = Not Applicable; SD = Standard Deviation; NR = Normal Ranges; L = Low; N = Normal; H = High. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 37 of 55 
 
Table XX - Cross-Tabulation of Biochemistry Abnormalities Versus Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Dose Group 
Parameter (unit) 
Visit 
 
Baseline 
Low 
Normal 
High 
Missing 
Total 
 
 
 
 
 
 
 
 
Treatment (N=X) XXXXXXXX (xxx) 
XXXX 
Low 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
 
Normal 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
High 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
Missing 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
Total 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
X (X.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
Percentages based on the number of volunteers in the relevant population. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 38 of 55 
 
Table XX – Liver Function: Summary of Volunteers Potentially Clinically Significant Abnormality During Inoculation Period 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Visit 
Parameter (unit) 
PCSA Criteria 
Treatment  
(N=X) 
n/N1(%) 
Treatment  
 (N=X) 
n/N1(%) 
Treatment  
 (N=X) 
n/N1(%) 
 
 
 
 
 
 
 
 
XXXX 
ALT (xxx) 
>3 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>5 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>8 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
AST (xxx) 
>3 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>5 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>8 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
ALT, AST 
ALT or AST >3 x ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
Total Bilirubin 
>2 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
ALT, AST, TBILI, 
DBILI 
ALT or AST >3 x ULN TBILI >2 x ULN 
at the same time point, together with a 
conjugated bilirubin fraction (DBILI / 
TBILI) > 35% 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of subjects in the relevant population. 
PCSA: Potentially Clinically Significant Abnormality, ULN: Upper Limit Normal; TBILI: Total Bilirubin, DBILI: Direct Bilirubin 
n: the total number of patients who met the PCSA criterion at the visit of interest 
N1: the number of patients for the treatment group who had that parameter assessed post-baseline at the visit of interest 
Inoculation period is defined as the time from the inoculum injection (Day-8) to the day before the IMP/rescue medication administration (for those who didn’t receive IMP) 
(Day-1) visit (included) 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 39 of 55 
 
Table XX – Liver Function: Summary of Volunteers Potentially Clinically Significant Abnormality Post IMP Administration 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Visit 
Parameter (unit) 
PCSA Criteria 
Treatment  
(N=X) 
n/N1(%) 
Treatment  
 (N=X) 
n/N1(%) 
Treatment  
 (N=X) 
n/N1(%) 
 
 
 
 
 
 
 
 
XXXX 
ALT (xxx) 
>3 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>5 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>8 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
AST (xxx) 
>3 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>5 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
>8 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
ALT, AST 
ALT or AST >3 x ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
Total Bilirubin 
>2 ULN 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
ALT, AST, TBILI, 
DBILI 
ALT or AST >3 x ULN TBILI >2 x ULN 
at the same time point, together with a 
conjugated bilirubin fraction (DBILI / 
TBILI) > 35% 
xx/xx (x.x%) 
xx/xx (x.x%) 
xx/xx (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of subjects in the relevant population. 
PCSA: Potentially Clinically Significant Abnormality, ULN: Upper Limit Normal; TBILI: Total Bilirubin, DBILI: Direct Bilirubin 
n: the total number of patients who met the PCSA criterion at the visit of interest 
N1: the number of patients for the treatment group who had that parameter assessed post-baseline at the visit of interest 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 40 of 55 
 
Table XX - Liver Function: Summary of Peak Readings During Inoculation Period 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Parameter (unit) 
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
ALT (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
AST (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Total Bilirubin (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
Inoculation period is defined as the time from the inoculum injection (Day-8) to the day before the IMP/rescue medication (for those who didn’t receive IMP) administration 
(Day-1) visit (included) 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 41 of 55 
 
Table XX - Liver Function: Summary of Peak Readings Since IMP Administration 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Parameter (unit) 
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
ALT (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
AST (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Total Bilirubin (unit) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 42 of 55 
 
Table XX - Liver Function: Summary of Time to Peak Readings Since IMP Administration in Days During Inoculation Period 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Parameter (unit) 
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
Time to Peak ALT (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
Time to Peak AST (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Time to Peak Total 
Bilirubin (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 43 of 55 
 
Table XX - Liver Function: Summary of Time to Peak Readings Since IMP Administration in Days 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Parameter (unit) 
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
Time to Peak ALT (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
Time to Peak AST (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Time to Peak Total 
Bilirubin (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 44 of 55 
 
Table XX - Urinalysis (Continuous) Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
Measured Values 
Change from Baseline 
Out of NR Count 
Dose Group 
Parameter (unit) 
Visit 
N Mean 
SD 
Median 
Min Max N Mean 
SD 
Median 
Min 
Max 
L 
N 
H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) XXXXXXXX (xxx) 
XXXX 
X X.XX 
X.XX 
X.XX 
X.X X.X X X.XX 
X.XX X.XX 
X.X X.X 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
Percentages based on the number of subjects in the relevant population. 
NA = Not Applicable; SD = Standard Deviation; NR = Normal Ranges; L = Low; N = Normal; H = High. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 45 of 55 
 
Table XX - Urinalysis (Categorical) Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
Visit 
Dose Group 
Parameter (unit) 
Category 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 46 of 55 
 
Table XX - Vital Signs Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
 
Measured Values 
Change from Baseline 
Dose Group 
Parameter (unit) 
Visit 
Timepoint 
N 
Mean 
SD 
Median 
Min 
Max 
N 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
XXXX 
X 
X.XX 
X.XX 
X.XX 
X.X 
X.X X X.XX 
X.XX 
X.XX 
X.X 
X.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 47 of 55 
 
Table XX - Abnormal Vital Signs Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
 
 
Clinical Assessment 
Dose Group 
Parameter (unit) 
Visit 
Timepoint 
Position 
Abnormal - NCS 
Abnormal - CS 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
XXXX 
XXXX 
X (X.X%) 
X (X.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of subjects in the relevant population. 
NCS = Not Clinically Significant; CS = Clinically Significant. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 48 of 55 
 
Table XX – Body Measures 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
Measured Values 
Change from Baseline 
 
Dose Group 
Parameter (unit) 
Visit 
N Mean 
SD 
Median 
Min Max N Mean 
SD 
Median 
Min 
Max 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Treatment (N=X) XXXXXXXX (xxx) 
XXXX 
X X.XX 
X.XX 
X.XX 
X.X X.X X X.XX 
X.XX X.XX 
X.X X.X 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 49 of 55 
 
Table XX - ECG Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
Measured Values 
Change from Baseline 
Dose Group 
Parameter (unit) 
Visit 
Timepoint 
N 
Mean 
SD 
Median 
Min 
Max 
N 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
XXXX 
X 
X.XX 
X.XX 
X.XX 
X.X 
X.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 50 of 55 
 
Table XX - ECG QTc Categorical Analyses 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
ECG 
Parameter 
Category 
(outside normal range) 
Treatment  
(N=X) 
Treatment  
(N=X) 
Treatment  
(N=X) 
 
 
 
 
 
QTcB 
Prolongation >30 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
Prolongation >60 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
>450 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
>480 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
QTcF 
Prolongation >30 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
Prolongation >60 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
>450 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
>480 msec 
XX (XX.X%) XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of volunteers in the relevant population. 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 51 of 55 
 
Table XX - ECG Clinical Assessment 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Dose Group 
Parameter (unit) 
Visit 
Timepoint 
Clinical Assessment 
Normal 
Abnormal NCS 
Abnormal CS 
Not Done 
 
 
 
 
 
 
 
 
Treatment (N=X) 
XXXXXXXX (xxx) 
XXXX 
XXXX 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of subjects in the relevant population. 
NA = Not Applicable; NCS = Not Clinically Significant; CS = Clinically Significant. 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 52 of 55 
 
Table XX - Malaria Clinical Score Summary by Question  
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
Visit 
Dose Group 
Question 
Reply 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
Headache 
Absent (0) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
Mild (1) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
Moderate (2) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
Severe (3) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
: 
: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
Percentages based on the number of volunteers in the relevant population. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Include all questions under Malaria Clinical Score questionnaire.  


Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 53 of 55 
 
Table XX – Malaria Clinical Total Score Results and Change from Baseline 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
 
 
 
Measured Values 
Change from Baseline 
Dose Group 
 
Visit 
 N 
Mean 
SD 
Median 
Min 
Max 
N 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment (N=X) 
 
XXXX 
 X 
X.XX 
X.XX 
X.XX 
X.X 
X.X 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing X 
SD: Standard Deviation 
Baseline is defined as the last scheduled observation prior to the first IMP administration. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 54 of 55 
 
Table XX – Peak Total Malaria Clinical Score and Time to Peak Total Malaria Clinical Score by Subject 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Dose Group 
Volunteer 
Total Malarial 
Clinical Score at 
IMP Dosing 
Peak Total Malaria 
Clinical Score 
During Study 
Time of Peak Malaria Clinical Total Score 
Study Days/s[a] 
Days after IMP[b] 
 
 
 
 
 
 
Treatment A 
XXX 
XXX 
XXX 
Day X 
Day X 
 
XXX 
XXX 
XXX 
Day X 
Day X 
 
 
 
 
 
 
Treatment B 
XXX 
XXX 
XXX 
Day X 
Day X 
 
XXX 
XXX 
XXX 
Day X 
Day X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing XX 
[a] Study days is related to the day when the subject signed the informed consent. 
[b] Days after IMP is related to the day since the IMP is administered. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Tables, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 55 of 55 
 
Table XX – Summary Peak Total Malaria Clinical Score and Time to Peak Total Malaria Clinical Score 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Parameter  
Statistic 
Treatment 
(N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
Treatment  
 (N=X) 
 
 
 
 
 
 
Peak Malaria Clinical Total Score 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
Time to Peak Malaria Clinical Total 
Score (days) 
 
 
 
 
 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Minimum 
X 
X 
X 
X 
 
Maximum 
X 
X 
X 
X 
 
 
 
 
 
 
Source: Listing XX 
SD: Standard Deviation  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 1 of 54 
 
 
MMV_MMV533_20_01: Mock Listings: Table of Contents 
 
Listing XX - Study Enrolment and Completion/Discontinuation .................................................................................................................................................................................... 4 
Listing XX - Visit Dates ....................................................................................................................................................................................................................................................... 5 
Listing XX - Dose Group Assignment ............................................................................................................................................................................................................................... 6 
Listing XX - Protocol Deviations ........................................................................................................................................................................................................................................ 7 
Listing XX - Analysis Population Assignment .................................................................................................................................................................................................................. 8 
Listing XX - In Patient Facility Admission and Discharge .............................................................................................................................................................................................. 9 
Listing XX - Demographics ............................................................................................................................................................................................................................................... 10 
Listing XX - Eligibility (Inclusion and Exclusion Criteria) .............................................................................................................................................................................................. 11 
Listing XX - Medical History ............................................................................................................................................................................................................................................. 12 
Listing XX - Beck Depression Index (BDI-2) .................................................................................................................................................................................................................. 13 
Listing XX - Pregnancy Test ............................................................................................................................................................................................................................................ 14 
Listing XX - Follicile Stimulating Hormone (FSH) ......................................................................................................................................................................................................... 15 
Listing XX - Serology Screening ...................................................................................................................................................................................................................................... 16 
Listing XX - Coagulation Screening ................................................................................................................................................................................................................................ 17 
Listing XX - Urine Drug Screening .................................................................................................................................................................................................................................. 18 
Listing XX - Alcohol Breath Test ...................................................................................................................................................................................................................................... 19 
Listing XX – Positive SARS-CoV-2 ................................................................................................................................................................................................................................. 20 
Listing XX - Prior Medications .......................................................................................................................................................................................................................................... 21 
Listing XX - Concomitant Medications ............................................................................................................................................................................................................................ 22 
Listing XX – Malaria Challenge Agent Administration .................................................................................................................................................................................................. 23 
Listing XX - Study Drug Administration .......................................................................................................................................................................................................................... 24 
Listing XX – Pharmacokinetic Concentrations .............................................................................................................................................................................................................. 25 
Listing XX – Pharmacokinetic Parameters .................................................................................................................................................................................................................... 26 
Listing XX – Pharmacodynamics Parameters ............................................................................................................................................................................................................... 27 
Listing XX – Pharmacodynamic – Parasitemia and Parasite Life Cycle Stages ...................................................................................................................................................... 28 
Listing XX - Adverse Events ............................................................................................................................................................................................................................................ 29 
Listing XX – Malaria Challenge Agent Related Inoculum Emergent Adverse Events ............................................................................................................................................. 30 
Listing XX – Inoculum Emergent Serious Adverse Events .......................................................................................................................................................................................... 32 
Listing XX – Treatment Emergent Serious Adverse Events ........................................................................................................................................................................................ 33 
Listing XX – Inoculum Emergent Adverse Events Leading to Study Discontinuation ............................................................................................................................................. 34 
Listing XX – Treatment Emergent Adverse Events Leading to Study Discontinuation ........................................................................................................................................... 35 
Listing XX – Inoculum Emergent Adverse Events of Special Interest (AESIs) ......................................................................................................................................................... 36 
Listing XX – Treatment Emergent Adverse Events of Special Interest (AESIs) ....................................................................................................................................................... 36 
Listing XX - Adverse Events During Inoculation Period ............................................................................................................................................................................................... 36 
Listing XX - Deaths ............................................................................................................................................................................................................................................................ 37 
Listing XX - Individual Haematology Results ................................................................................................................................................................................................................. 38 
Listing XX - Individual Abnormal Haematology Results ............................................................................................................................................................................................... 39 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 2 of 54 
 
Listing XX - Individual Biochemistry Results ................................................................................................................................................................................................................. 40 
Listing XX - Individual Abnormal Biochemistry Results ............................................................................................................................................................................................... 41 
Listing XX - Individual Liver Function Related Parameters ......................................................................................................................................................................................... 42 
Listing XX - Individual Abnormal Coagulation Results ................................................................................................................................................................................................. 43 
Listing XX - Individual Urinalysis Results (dipstick) ...................................................................................................................................................................................................... 44 
Listing XX - Individual Abnormal Urinalysis Results (dipstick) .................................................................................................................................................................................... 45 
Listing XX - Individual Urine Microscopy Results ......................................................................................................................................................................................................... 46 
Listing XX - Individual Abnormal Urine Microscopy Results ....................................................................................................................................................................................... 47 
Listing XX - Individual Vital Signs Results ..................................................................................................................................................................................................................... 48 
Listing XX - Individual Abnormal Vital Signs Results ................................................................................................................................................................................................... 49 
Listing XX - Individual Body Measurement Results ...................................................................................................................................................................................................... 50 
Listing XX - Individual ECG Parameters Results .......................................................................................................................................................................................................... 51 
Listing XX - Individual Abnormal ECG Findings ............................................................................................................................................................................................................ 52 
Listing XX - Physical Examination................................................................................................................................................................................................................................... 53 
Listing XX – Malaria Clinical Score Results ................................................................................................................................................................................................................... 54 
 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 3 of 54 
 
Notes: 
• 
Dose group names: 
▪ 
MMV 533 (20 mg) 
▪ 
MMV 533 (35 mg) 
▪ 
MMV 533 (100 mg) 
▪ 
MMV 533 (160 mg)  
• 
Ordering of “Individual Safety” data:  
o 
Dose group – Present as sub-heading rather than separate column 
o 
Volunteer (ascending) 
o 
Parameter/Assessment  
▪ 
Non-laboratory to be ordered as ordered on the CRF 
▪ 
Laboratory parameters to be ordered alphabetically 
o 
Visit (chronological) 
o 
Timepoint (chronological) 
• 
Ordering of all other data:  
o 
Gose group – Present as sub-heading rather than separate column 
o 
Volunteer (ascending) 
o 
Visit (chronological) 
o 
Timepoint (chronological) 
o 
Assessment  (alphabetical) 
• 
Footnotes may be added/amended as required 
• 
Column widths and text-wrapping may be altered in final output to best present the data. 
• 
Dates and Times 
• 
Date and times will be presented in ISO format: 
o 
Date: YYYY-MM-DD 
o 
Time: HH:MM (24-hour clock) 
o 
Date Time: YYYY-MM-DD / HH:MM or YYYY-MM-DD (XX) / HH:MM (If Study Day is included)  
For a Date/Time field, if there is no time then only the date portion will be presented 
• 
Results may be split over multiple pages if all columns cannot be fit onto a single page. 
• 
If there is no data for a particular listing (for example, SAEs, etc.), populate the listing with “No Serious Treatment Emergent Adverse Events reported.”  
• 
Refer to Statistical Deliverables document for output numbering 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 4 of 54 
 
Listing XX - Study Enrolment and Completion/Discontinuation 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
  
Volunteer 
Number 
Date/Time of 
Informed Consent  
(YYYY-MM-DD /  
HH:MM) 
Protocol 
Version 
Date/Time of 
Inoculation 
(YYYY-MM-DD / 
HH:MM) 
Date/Time of  
IMP Treatment 
(YYYY-MM-DD / 
HH:MM) 
Date/Time of  
Rescue 
Medication 
Administered 
(YYYY-MM-DD / 
HH:MM) 
Did the 
Volunteer 
Complete 
the Study? 
Date of  
Completion/Early 
Termination 
(YYYY-MM-DD) 
Primary Reason 
for Study 
Discontinuation /  
     Related to 
COVID-19 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
Yes 
YYYY-MM-DD 
XXXXXX / 
      No 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
Yes 
YYYY-MM-DD 
XXXXXX / 
      No 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
Yes 
YYYY-MM-DD 
XXXXXX / 
      No 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
No 
YYYY-MM-DD 
XXXXXX / 
      No 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
Yes 
YYYY-MM-DD 
XXXXXX / 
      No 
XXXX 
YYYY-MM-DD / 
HH:MM 
XXXXXX 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
YYYY-MM-DD / 
HH:MM 
Yes 
YYYY-MM-DD 
XXXXXX / 
      No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 5 of 54 
 
Listing XX - Visit Dates 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer Number 
Visit 
Date (d) of Visit 
 
 
 
Dose Group 
 
 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 6 of 54 
 
Listing XX - Dose Group Assignment 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer Number 
Dose Group 
 
 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Note for Programmer:  Do not group by Dose Group. Sort by Volunteer Number only (ascending) 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 7 of 54 
 
Listing XX - Protocol Deviations 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
PD 
No. 
Date of Deviation (d) 
(YYYY-MM-DD 
(XX)) 
COVID-19 Related 
Deviation/ 
Describe/ 
Visit Relates to 
 
Deviation 
Classification/ 
Deviation Category 
Deviation Description 
Action Required/ 
Outcome 
Ethics Committee 
Reported/ 
Date of Reporting (d) 
(YYYY-MM-DD (XX)) 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Major/ 
Informed Consent 
Abcd 
Abcd/ 
Efgh 
No 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Eligibility 
Abcd 
Abcd/ 
Efgh 
Yes/ 
YYYY-MM-DD (XX) 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Study Procedure 
Not Done 
Abcd 
Abcd/ 
Efgh 
No 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Visit Performed 
Outside of Window 
Abcd 
Abcd 
Abcd/ 
Efgh 
No 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Study Procedure 
Done out of Window 
Abcd 
Abcd/ 
Efgh 
No 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Safety Reporting 
Abcd 
Abcd/ 
Efgh 
No 
 
X 
YYYY-MM-DD (XX) 
Yes / No/ 
XXXXX/ 
Day X 
 
Minor/ 
Concomitant 
Medication 
Abcd 
Abcd/ 
Efgh 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Description of Protocol Deviation presented as verbatim. PD No. = Protocol deviation number. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 8 of 54 
 
Listing XX - Analysis Population Assignment 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
Full Analysis Set 
Safety Set 
PK Analysis Set 
PD Analysis Set 
PK/PD Analysis Set 
Inoculation Set 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Full Analysis Set: All enrolled volunteers 
Safety Set: All enrolled volunteers who received at least one dose (full or partial) of IMP 
PK Analysis Set: All volunteers with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any 
              study treatment and experienced no protocol deviations with relevant impact on PK data 
 
PD Analysis Set: All volunteers with any available PD data, who received any study treatment and experienced no protocol deviations with relevant  
              impact on PD data 
 
PK/PD Analysis Set: All volunteers from the PK set and all subjects from the PD set 
 
Inoculation Set: All volunteers inoculated with the P. falciparum challenge agent 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 9 of 54 
 
Listing XX - In Patient Facility Admission and Discharge 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
  
Volunteer 
Number 
Date (d) / Time of 
Admission 
(YYYY-MM-DD (XX) 
HH:MM) 
Date (d) / Time of 
Discharge 
(YYYY-MM-DD (XX) 
HH:MM) 
 
 
 
Dose Group 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
XXXX 
YYYY-MM-DD (XX)/ 
HH:MM 
YYYY-MM-DD (XX)/ 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 10 of 54 
 
Listing XX - Demographics 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
Age 
(Years) 
Sex 
Is the Volunteer of  
Childbearing Potential?/ 
Is the Volunteer menopausal? 
Race 
Ethnicity 
Height 
(cm) 
[Screening 
/ Day -1] 
Weight 
(kg) 
[Screening / 
Day -1] 
Body Mass 
Index 
(kg/m2) 
 
 
 
 
 
 
 
 
 
Dose Group 
 
XXXX 
XX 
Female 
No/No 
White 
Not Hispanic or 
Latino 
XXX 
XX.X / XX.X 
XX.X / XX.X 
XXXX 
XX 
Male 
- 
Asian 
Not Hispanic or 
Latino 
XXX 
XX.X / XX.X 
XX.X / XX.X 
XXXX 
XX 
Female 
Yes/No 
Other: XXXX 
Not Hispanic or 
Latino 
XXX 
XX.X / XX.X 
XX.X / XX.X 
XXXX 
XX 
Male 
- 
Black or African 
American 
Not Hispanic or 
Latino 
XXX 
XX.X / XX.X 
XX.X / XX.X 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Age at Screening visit 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 11 of 54 
 
Listing XX - Eligibility (Inclusion and Exclusion Criteria) 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
Visit 
Did the volunteer meet ALL 
inclusion criteria and NO 
exclusion criteria? 
 
 
 
Dose Group 
XXXX 
Day -1 
Yes 
 
Day 1 
No: Inclusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 12 of 54 
 
Listing XX - Medical History 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
 Number 
MH 
No 
Medical History Verbatim / 
   System Organ Class / 
      Preferred Term 
Start Date of Medical 
History Event  
(YYYY-MM-DD) 
End Date of 
Medical History 
Event  
 (YYYY-MM-DD) 
Volunteer Taking Medication  
for The Medical History Event? 
 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
X 
XXXXXXXXXXXXX / 
   XXXXXXXXXXXXXXX / 
      XXXXXXXXXXXXXXXXX 
YYYY-MM-DD 
Ongoing 
Yes 
XXXX 
X 
XXXXXXXXXXXXX / 
   XXXXXXXXXXXXXXX / 
      XXXXXXXXXXXXXXXXX 
YYYY-UNK-UN 
YYYY-UNK-UN 
No 
XXXX 
etc. 
 
 
- 
 
 
 
 
 
 
 
Notes:  Medical conditions were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
UN = Unknown day; UNK= Unknown month; UNKK = Unknown year; MH No: Medical History Number; UN: Unknown 
                                                                                           
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 13 of 54 
 
Listing XX - Beck Depression Index (BDI-2) 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer 
Number 
Visit 
Date (d) / Time of Completion 
(YYYY-MM-DD (XX) / HH:MM) 
Question 
Result 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
Visit 
YYYY-MM-DD (XX) / HH:MM 
1. Sadness 
0 I do not feel sad 
 
 
 
2. Pessimism 
1 I feel more discouraged about 
my future than I used to be. 
 
 
 
…. 
 
 
 
 
21. Loss of Interest in Sex 
 
 
 
 
Total Score  
XX 
 
Visit 
Not Done: XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 14 of 54 
 
Listing XX - Pregnancy Test 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set (Women of Childbearing Potential Only) 
 
 
Volunteer  
Number Visit 
Date (d) / Time  of  
Pregnancy Test 
(YYYY-MM-DD (XX) HH:MM) 
Sample Type 
Result 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
Screening 
YYYY-MM-DD (XX) HH:MM 
Urine 
Negative 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 15 of 54 
 
Listing XX - Follicile Stimulating Hormone (FSH) 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set (Post-menopausal women only) 
 
 
Volunteer  
Number 
Visit 
Date (d) / Time of Sampling 
(YYYY-MM-DD (XX) / HH:MM) 
Result (IU/L) 
 
 
 
 
Dose Group 
 
 
XXXX 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 16 of 54 
 
Listing XX - Serology Screening 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer 
Number 
Visit 
Date (d) / Time of Sampling 
(YYYY-MM-DD (XX) / HH:MM) 
Parameter 
Result 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
Visit 
YYYY-MM-DD (XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 17 of 54 
 
Listing XX - Coagulation Screening 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer 
Number 
Parameter (unit) 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting  
Result 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
Screening 
YYYY-MM-DD(XX) / HH:MM 
Yes/No 
X.XX 
- 
- 
 
Parameter (unit) 
Screening 
YYYY-MM-DD(XX) / HH:MM 
Yes/No 
X.XX 
H 
NCS 
 
 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
Screening 
Not Done: Reason 
Yes/No 
- 
- 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 18 of 54 
 
Listing XX - Urine Drug Screening 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
 
Volunteer  
Number 
Visit 
Date (d) / Time of  
Drug Assessment 
(YYYY-MM-DD (XX) HH:MM) 
Parameter 
Result 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
Screening 
YYYY-MM-DD (XX) HH:MM 
Amphetamines 
Negative 
 
 
 
Benzodiazepines 
Negative 
 
 
 
Cocaine 
Negative 
 
 
 
Methadone 
Not Done 
 
 
 
… 
 
 
 
 
Paracetamol 
Negative 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 19 of 54 
 
Listing XX - Alcohol Breath Test  
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer  
Number 
Visit 
Date (d) / Time of  
Assessment 
(YYYY-MM-DD (XX) HH:MM) 
Result 
 
 
 
 
Dose Group 
 
 
XXXX 
Screening 
YYYY-MM-DD (XX) HH:MM 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 20 of 54 
 
Listing XX – Positive SARS-CoV-2  
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer  
Number 
Visit 
Date (d) / Time of  
Test 
(YYYY-MM-DD (XX) HH:MM) 
Type of Test 
 
 
 
 
 
 
Dose Group 
 
 
 
XXXX 
Screening 
YYYY-MM-DD (XX) HH:MM 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 21 of 54 
 
Listing XX - Prior Medications 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
Med 
No 
Medication Name Verbatim/ 
   Preferred Name*/ 
      ATC Class* 
Start Date (d) /  
   Start Time / 
      End Date (d) /  
         End Time  
Dose 
(unit) 
Route 
Frequency 
Indication / 
     Indication 
Category 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
X XXXXXX /  
   XXXXXXXX /  
      XXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) /  
         HH:MM 
XX 
(xx) 
Abcd 
Abcd 
Abcd /  
     Abcd 
XXXX 
X XXXXXX /  
   XXXXXXXX /  
      XXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) /  
         HH:MM 
XX 
(xx) 
Abcd 
Abcd 
Abcd  / 
       Abcd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  *Medications were coded to preferred name and ATC class using WHO DD version 20YY:MM (ATC Class Level 3) 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Prior medications with an end date after the administration of IMP are also classified as concomitant medication.  
Med No: Medication Number; UN: Unknown 
                                                                                           
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 22 of 54 
 
Listing XX - Concomitant Medications 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Volunteer Number 
Med 
No 
Medication Name Verbatim/ 
   Preferred Name*/ 
      ATC Class* 
Start Date (d) /  
   Start Time / 
      End Date (d) /  
         End Time  
Dose 
(unit) 
Route 
Frequency 
Indication / 
     Indication 
Category 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
X 
XXXXXX /  
   XXXXXXXX /  
      XXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) /  
         HH:MM 
XX 
(xx) 
Abcd 
Abcd 
Abcd / 
     Abcd 
XXXX 
X 
XXXXXX /  
   XXXXXXXX /  
      XXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
XX 
(xx) 
Abcd 
Abcd 
Abcd / 
     Abcd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  *Medications were coded to preferred name and Anatomical Therapeutic Class (ATC) using WHO DD version 2018:03 (ATC Class Level 3) 
 
Study Day (d): Number of days relative to date of first administration of Investigational Medicinal Product (IMP), where the day of first administration = 1. 
 
Medications with a start date prior to administration of IMP were also classified as prior medications.  
Med No: Medication Number; UN: Unknown 
                                                                                           
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 23 of 54 
 
Listing XX – Malaria Challenge Agent Administration 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer 
Number 
Visit 
Was Malaria Challenge 
Agent Administered? 
Date (d) / Time 
of Inoculation 
(YYYY-MM-DD (XX) / HH:MM) 
 
Total Volume of 
Inoculation 
Administered 
(mL) 
 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
 
 
XXXX 
Day 1 
No: XXXX 
 
 
XX 
 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 24 of 54 
 
Listing XX - Study Drug Administration 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
 
Volunteer 
Number 
Visit 
Was IMP Administered? 
Date (d) / Start Time 
of Administration 
(YYYY-MM-DD (XX) / HH:MM) 
 
Total Amount 
Administered 
(mg) 
Was Volunteer fasted 
for at least 8 hours? 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
Yes 
 
XXXX 
Day 1 
No: XXXX 
 
 
XX 
Yes 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
Yes 
 
XXXX 
Day 1 
Yes 
YYYY-MM-DD (XX) / HH:MM 
 
XX 
Yes 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
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Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 25 of 54 
 
Listing XX – Pharmacokinetic Concentrations 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set 
 
Matric: Plasma; Analyte: MMV533 
 
 
Concentration (units) 
Volunteer 
Number 
Visit 
Pre-dose 
0.5h 
1h 
2h 
….. 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Day 1 
 
 
 
 
 
 
XXXX 
Day 1 
 
 
 
 
 
 
XXXX 
Day 1 
 
 
 
 
 
 
XXXX 
Day 1 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Repeat for metabolites (MMV022 and MMV023). Replace Plasma to Metabolite 
in Matric and replace MMV533 with MMV022 and MMV023 accordingly. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 26 of 54 
 
Listing XX – Pharmacokinetic Parameters 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set 
 
Matric: Plasma; Analyte: MMV533 
Volunteer 
Number 
 
AUC0-∞ 
(unit) 
… 
… 
tmax (unit) 
 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Note:  Repeat for metabolites (MMV022 and MMV023). Replace Plasma to Metabolite 
in Matric and replace MMV533 with MMV022 and MMV023 accordingly. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 27 of 54 
 
Listing XX – Pharmacodynamics Parameters 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
Matric: Plasma; Analyte: MMV533 
Volunteer 
Number 
Visit 
Timepoint 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / 
HH:MM) 
 
CP of PCR 
Replicates 
Calculated 
Parasites/ 500μl of 
Packed RBCs 
Geometric Mean of 
Parasites/ 500μl of 
Packed RBCs 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Day -8 
Pre inoculation YYYY-MM-DD(XX) /  
HH:MM 
 
ND 
ND 
XX 
 
 
 
 
 
ND 
ND 
 
 
 
 
 
 
XX 
XX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: ND: Non-detected. 
                                                                                         
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Notes: 
• 
Individual values for 18S qPCR with nominal timepoints and actual sampling times will be presented in data 
listings for all subjects.  


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 28 of 54 
 
Listing XX – Pharmacodynamic – Parasitemia and Parasite Life Cycle Stages 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set  
 
 
Volunteer 
Number 
Parameter (unit) 
Visit  
Timepoint 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / 
HH:MM) 
CP of PCR 
Replicates 
Copies of 
transcripts/ 
500μl pRBCs 
Geometric Mean of 
Copies of 
transcripts/ 500μl 
pRBCs 
 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
18S qPCR (unit) 
 
Day -8 
Pre inoculation 
YYYY-MM-DD(XX) / 
HH:MM 
ND 
XX 
ND 
XX 
XX 
 
 
 
Day -4 
 
YYYY-MM-DD(XX) / 
HH:MM 
XX 
XX 
XX 
XX 
XX 
 
 
 
Day -3 
am 
YYYY-MM-DD(XX) / 
HH:MM 
XX 
XX 
XX 
 
 
 
 
pm 
YYYY-MM-DD(XX) / 
HH:MM 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: ND: Non-detected. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
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Programming Notes: 
• 
Individual values for total parasitemia (18S qPCR) and parasite life cycle stages (pfs25, pfMGET and sbp1 qRT-
PCR) with nominal timepoints and actual sampling times will be presented in data listings for all subjects.  


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 29 of 54 
 
Listing XX - Adverse Events 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
IETE/ 
TEAE/ 
SAE 
Severity / 
   Action Taken with IMP /  
    Other Actions Taken /  
      Outcome 
  
Related to:  
IMP /  
Rescue Medication /  
Malaria Challenge Agent /  
Procedure 
  
AE Lead to Study 
Discontinuation /  
COVID-19 Related 
 
  
 
 
 
 
   
Dose Group 
 
 
 
 
   
XXXX 
X XXXXXXXXXXXXXXXXX*/ 
   XXXXXXXXXXXXXXXXXXXX*/ 
      XXXXXXXXXXXXXXXXXXXXXX* 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
Yes/ 
No/ 
No 
Grade 1 - Mild /  
   No Action taken / 
Medical/Surgical Procedure Taken:  
   XXXX  /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
Yes/ 
Yes/ 
 No 
Grade 1 - Mild /  
   No Action taken / 
Medication Taken; Medical/Surgical 
Procedure Taken: XXXX   
Other Action Taken: YYYYY /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
  
 
 
 
 
   
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
A treatment-emergent adverse event is defined as an AE that occurred on or worsened following first administration of IMP 
An inoculum-emergent adverse event is defined as an AE that occurred on of worsened following the administration of the challenge agent for the inoculation up to the 
end-of-study (EOS) visit (inclusive). 
 
AE No: Adverse Event Number; IMP: Investigational Medicinal Product SAE: serious adverse event; IEAE: Inoculum-emergent adverse event; TEAE: Treatment-
emergent adverse event 
*indicates AE occurred during inoculation period. 
            
                  
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Programming Notes: 
• 
For the first draft, fit all columns to the one page, adjusting the font no less than 8pt. Page margins may also be narrowed to aide in formatting. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 30 of 54 
 
Listing XX – Malaria Challenge Agent Related Inoculum Emergent Adverse Events 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
 
SAE 
Severity / 
   Action Taken with IMP /  
    Other Actions Taken /  
      Outcome 
  
Related to:  
IMP /  
Rescue Medication /  
Malaria Challenge Agent /  
Procedure 
  
AE Lead to Study 
Discontinuation /  
COVID-19 Related 
 
  
 
 
 
 
   
Dose Group 
 
 
 
 
   
XXXX 
X XXXXXXXXXXXXXXXXX*/ 
   XXXXXXXXXXXXXXXXXXXX*/ 
      XXXXXXXXXXXXXXXXXXXXXX* 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No / No Grade 1 - Mild /  
   No Action taken / 
Medical/Surgical Procedure Taken:  
   XXXX  /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
Yes / 
No 
Grade 1 - Mild /  
   No Action taken / 
Medication Taken; Medical/Surgical 
Procedure Taken: XXXX   
Other Action Taken: YYYYY /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
  
 
 
 
 
   
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 An inoculum-emergent adverse event is defined as an AE that occurred on of worsened following the administration of the challenge agent for the inoculation up to 
the end-of-study (EOS) visit (inclusive). 
 
AE No: Adverse Event Number; IMP: Investigational Medicinal Product SAE: serious adverse event;  
*indicates AE occurred during inoculation period. 
            
                  
Database Export Date: YYYY-MM-DD 
Page X of Y                               
Program: filepath_name (Version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
Programming Notes: 
• 
For the first draft, fit all columns to the one page, adjusting the font no less than 8pt. Page margins may 
also be narrowed to aide in formatting. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 31 of 54 
 
Listing XX – IMP Related Treatment Emergent Adverse Events 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Volunteer 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
 
SAE 
Severity / 
   Action Taken with IMP /  
    Other Actions Taken /  
      Outcome 
  
Related to:  
IMP /  
Rescue Medication /  
Malaria Challenge Agent /  
Procedure 
  
AE Lead to Study 
Discontinuation /  
COVID-19 Related 
 
  
 
 
 
 
   
Dose Group 
 
 
 
 
   
XXXX 
X XXXXXXXXXXXXXXXXX*/ 
   XXXXXXXXXXXXXXXXXXXX*/ 
      XXXXXXXXXXXXXXXXXXXXXX* 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No / No Grade 1 - Mild /  
   No Action taken / 
Medical/Surgical Procedure Taken:  
   XXXX  /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
Yes / 
No 
Grade 1 - Mild /  
   No Action taken / 
Medication Taken; Medical/Surgical 
Procedure Taken: XXXX   
Other Action Taken: YYYYY /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  No /  
  No 
 
  
 
 
 
 
   
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 A treatment-emergent adverse event is defined as an AE that occurred on or worsened following first administration of IMP 
 
AE No: Adverse Event Number; IMP: Investigational Medicinal Product SAE: serious adverse event;  
*indicates AE occurred during inoculation period. 
            
                  
Database Export Date: YYYY-MM-DD 
Page X of Y                               
Program: filepath_name (Version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
 
 
Programming Notes: 
• 
For the first draft, fit all columns to the one page, adjusting the font no less than 8pt. Page margins may also 
be narrowed to aide in formatting. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 32 of 54 
 
Listing XX – Inoculum Emergent Serious Adverse Events 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunte
er 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
Overall AE 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
SAE  
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
Death? 
Life 
Threatening? 
Prolonged 
Hospitalisat
ion? 
Persistent 
or 
Significant 
Disability of 
Incapacity 
Congenital 
Anomaly of 
Birth 
Defect 
Possible 
Hy’s Law 
Other 
Medically 
Important 
Event 
 
  
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
 
 
XXXX 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
No 
Yes 
No 
No 
No 
No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
No 
No 
No 
No 
No 
Yes: XXXX 
 
  
 
 
 
 
 
 
 
 
 
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
An inoculum-emergent adverse event is defined as an AE that occurred on of worsened following the administration of the challenge agent for the inoculation up to the 
end-of-study (EOS) visit (inclusive). 
 
AE No: Adverse Event Number; SAE: serious adverse event 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
Programming Notes:  
• 
If there is no record for SAE, please display as” “No Serious Adverse Event Reported”. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 33 of 54 
 
Listing XX – Treatment Emergent Serious Adverse Events 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Volunte
er 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
Overall AE 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
SAE  
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
Death? 
Life 
Threatening? 
Prolonged 
Hospitalisat
ion? 
Persistent 
or 
Significant 
Disability of 
Incapacity 
Congenital 
Anomaly of 
Birth 
Defect 
Possible 
Hy’s Law 
Other 
Medically 
Important 
Event 
 
  
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
 
 
XXXX 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
No 
Yes 
No 
No 
No 
No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
No 
No 
No 
No 
No 
Yes: XXXX 
 
  
 
 
 
 
 
 
 
 
 
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
A treatment-emergent adverse event is defined as an AE that occurred on or worsened following first administration of IMP. 
 
AE No: Adverse Event Number; SAE: serious adverse event 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y  
 
 
Programming Notes:  
• 
If there is no record for SAE, please display as” “No Serious Adverse Event Reported”. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 34 of 54 
 
Listing XX – Inoculum Emergent Adverse Events Leading to Study Discontinuation 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Volunteer 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
 
SAE 
Severity / 
   Action Taken with IMP /  
    Other Actions Taken /  
      Outcome 
  
Related to:  
IMP /  
Rescue Medication /  
Malaria Challenge Agent /  
Procedure 
  
AE Lead to Study 
Discontinuation /  
COVID-19 Related 
 
  
 
 
 
 
   
Dose Group 
 
 
 
 
   
XXXX 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
Grade 1 - Mild /  
   No Action taken / 
Medical/Surgical Procedure Taken:  
   XXXX  /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  Yes /  
  No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
No 
Grade 1 - Mild /  
   No Action taken / 
Medication Taken; Medical/Surgical 
Procedure Taken: XXXX   
Other Action Taken: YYYYY /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  Yes /  
  No 
 
  
 
 
 
 
   
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 An inoculum-emergent adverse event is defined as an AE that occurred on of worsened following the administration of the challenge agent for the inoculation up to 
the end-of-study (EOS) visit (inclusive) 
 
AE No: Adverse Event Number; IMP: Investigational Medicinal Product SAE: serious adverse event; TEAE: Treatment-emergent adverse event 
            
                  
Database Export Date: YYYY-MM-DD 
Page X of Y                            
Program: filepath_name (Version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
 
Programming Notes: 
• 
For the first draft, fit all columns to the one page, adjusting the font no less than 8pt. Page 
margins may also be narrowed to aide in formatting. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 35 of 54 
 
Listing XX – Treatment Emergent Adverse Events Leading to Study Discontinuation 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Volunteer 
Number 
AE 
No 
Adverse Event Verbatim/ 
   System Organ Class/ 
      Preferred Term 
 
Start Date (d) / 
   Start Time / 
      End Date (d) / 
         End Time 
 
SAE 
Severity / 
   Action Taken with IMP /  
    Other Actions Taken /  
      Outcome 
  
Related to:  
IMP /  
Rescue Medication /  
Malaria Challenge Agent /  
Procedure 
  
AE Lead to Study 
Discontinuation /  
COVID-19 Related 
 
  
 
 
 
 
   
Dose Group 
 
 
 
 
   
XXXX 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      DD-MMM-YYYY (xx) / 
         HH:MM 
No 
Grade 1 - Mild /  
   No Action taken / 
Medical/Surgical Procedure Taken:  
   XXXX  /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  Yes /  
  No 
 
X XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXXXXXXXXX 
DD-MMM-YYYY (xx) /  
   HH:MM / 
      Ongoing 
No 
Grade 1 - Mild /  
   No Action taken / 
Medication Taken; Medical/Surgical 
Procedure Taken: XXXX   
Other Action Taken: YYYYY /  
      Recovered/Resolved 
Related /  
   Not Related /  
     Not Related /  
       Not Related 
  Yes /  
  No 
 
  
 
 
 
 
   
Notes:  Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version XX.X. 
 
Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
A treatment-emergent adverse event is defined as an AE that occurred or worsened following first administration of IMP 
 
AE No: Adverse Event Number; IMP: Investigational Medicinal Product SAE: serious adverse event; TEAE: Treatment-emergent adverse event 
            
                  
Database Export Date: YYYY-MM-DD 
Page X of Y                            
Program: filepath_name (Version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
 
Programming Notes: 
• 
For the first draft, fit all columns to the one page, adjusting the font no less than 8pt. Page 
margins may also be narrowed to aide in formatting. 
• 
If time is unknown then present date only 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 36 of 54 
 
Listing XX – Inoculum Emergent Adverse Events of Special Interest (AESIs) 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Listing to take same format as the Inoculum Emergent Adverse Events listing, restricted to AESIs only 
 
Listing XX – Treatment Emergent Adverse Events of Special Interest (AESIs) 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Listing to take same format as the Treatment Emergent Adverse Events listing, restricted to AESIs only 
 
Listing XX - Adverse Events During Inoculation Period 
Protocol: MMV_MMV533_20_01 
Population: Full Analysis Set 
 
Listing to take same format as the Inoculum Emergent Adverse Events listing  
 
 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 37 of 54 
 
Listing XX - Deaths 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
Volunteer 
Number 
Date (d) of Death 
(YYYY-MM-DD) 
Primary Cause of Death 
 
 
 
 
 
Dose Group 
 
 
XXXX 
YYYY-MM-DD(XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IUIMP, where the day of first administration = 1.  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
Programming Note:  
• Listing only to be prepared if there is one or more death reported. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 38 of 54 
 
Listing XX - Individual Haematology Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting 
Result 
Actual 
Change from 
Baseline 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Screening 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
- 
- 
 
 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
H 
NCS 
 
 
XXXX 
Not Done: Reason 
- 
- 
- 
- 
- 
 
 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
No 
X.XX 
X.XX 
- 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 39 of 54 
 
Listing XX - Individual Abnormal Haematology Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection 
(YYYY-MM-DD (XX) / HH:MM) 
Fasting 
Result 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
H 
NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 40 of 54 
 
Listing XX - Individual Biochemistry Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting 
Result 
Actual 
Change from 
Baseline 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Screening 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
- 
- 
 
 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
H 
NCS 
 
 
XXXX 
Not Done: Reason 
- 
- 
- 
- 
- 
 
 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
No 
X.XX 
X.XX 
- 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 41 of 54 
 
Listing XX - Individual Abnormal Biochemistry Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting  
Result 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
H 
NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 42 of 54 
 
Listing XX - Individual Liver Function Related Parameters 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting 
Result 
Actual 
Change from 
Baseline 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Screening 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
- 
- 
 
 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes 
X.XX 
NA 
H 
NCS 
 
 
XXXX 
Not Done: Reason 
- 
- 
- 
- 
- 
 
 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
No 
X.XX* 
X.XX 
- 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
             *Peak Results. 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 43 of 54 
 
Listing XX - Individual Abnormal Coagulation Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Fasting  
Result 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
Yes/No 
X.XX 
H 
NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 44 of 54 
 
Listing XX - Individual Urinalysis Results (dipstick) 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Result 
Actual 
Change from 
Baseline 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Screening 
YYYY-MM-DD(XX) / HH:MM 
X.XX 
NA 
- 
- 
 
 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
X.XX 
NA 
H 
NCS 
 
 
XXXX 
Not Done: Reason 
- 
- 
- 
- 
 
 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
X.XX 
X.XX 
- 
- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 45 of 54 
 
Listing XX - Individual Abnormal Urinalysis Results (dipstick) 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[ Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Result 
Range 
Indicator 
Volunteer 
Menstruating? 
Clinical 
Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
Parameter (unit) 
[XXX-XXX] 
Day -1 
YYYY-MM-DD(XX) / HH:MM 
X.XX 
H 
No 
NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 46 of 54 
 
Listing XX - Individual Urine Microscopy Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[ Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Result 
Actual 
Change from 
Baseline 
Range 
Indicator 
Was Volunteer 
Menstruating? 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 47 of 54 
 
Listing XX - Individual Abnormal Urine Microscopy Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
[ Normal Range] 
Visit 
Date (d) / Time of 
Sample Collection  
(YYYY-MM-DD (XX) / HH:MM) 
Result 
Range 
Indicator 
Clinical 
Significance 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; A = Abnormal; E = Eligibility; H = High; HE = High/Eligibility; L = Low; NCS = Not Clinically Significant; CS = Clinically Significant  
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 48 of 54 
 
Listing XX - Individual Vital Signs Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
Visit 
Timepoint 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / HH:MM) 
Position 
Result 
Actual 
Change from 
Baseline 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
 
 
 
YYYY-MM-DD (XX) / HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; NCS = Not Clinically Significant; CS = Clinically Significant 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 49 of 54 
 
Listing XX - Individual Abnormal Vital Signs Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
Visit 
Timepoint 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / HH:MM) 
Position 
Result 
Clinical 
Assessment 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
 
 
 
YYYY-MM-DD(XX) / HH:MM 
 
 
NCS 
 
 
 
 
 
 
 
CS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; NCS = Not Clinically Significant; CS = Clinically Significant 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 50 of 54 
 
Listing XX - Individual Body Measurement Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
Visit 
 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / HH:MM) 
 
Result 
Actual 
Change from 
Baseline 
 
 
 
 
  
 
 
 
 
Dose Group 
 
  
 
 
 
 
XXXX 
 
 
 YYYY-MM-DD (XX) / HH:MM 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; NCS = Not Clinically Significant; CS = Clinically Significant 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 51 of 54 
 
Listing XX - Individual ECG Parameters Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter 
(unit) 
Visit 
Timepoint Replicate Number 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / 
HH:MM) 
Result 
Actual 
Change from 
Baseline 
Abnormal Description /  
Clinical Significance 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
PR  (msec) 
XXXX 
XXXX 
- 
YYYY-MM-DD(XX) / HH:MM 
XXX 
NA 
- 
 
 
XXXX 
XXXX 
- 
Not Done: Reason 
- 
- 
- 
 
 
XXXX 
XXXX 
1 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
 
 
2 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
 
 
3 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
 
 
Average 
- 
XXX 
XXX 
- 
 
 
XXXX 
XXXX 
 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
XXXX 
XXXX 
 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
 
 
 
 
 
 
 
 
QRS (msec) XXXX 
XXXX 
 
YYYY-MM-DD(XX) / HH:MM 
XXX 
- 
- 
 
 
XXXX 
XXXX 
 
YYYY-MM-DD(XX) / HH:MM 
XXX 
XXX 
- 
 
 
 
 
 
 
 
 
 
 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interpretation XXXX 
XXXX 
- 
YYYY-MM-DD(XX) / HH:MM 
Normal 
- 
- 
 
 
XXXX 
XXXX 
- 
Not Done: Reason 
- 
- 
- 
 
 
XXXX 
XXXX 
- 
YYYY-MM-DD(XX) / HH:MM 
Abnormal 
- 
Abcd / CS 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA: Not Applicable; NCS: Not Clinically Significant; CS: Clinically Significant 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 
Programming Note:  
•Listing to incorporate both single and triplicate ECG results 
• All Parameters, including RR interval (msec), Heart Rate(bpm), PR Interval (msec), QRS Interval (msec), QT Interval (msec), QTcB (msec) and QTcF (msec) will be displayed in this listing. 
•In addition, the ECG interpretation will be included as a separate parameter and “Abnormal Description” will be specified if the result if abnormal. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 52 of 54 
 
Listing XX - Individual Abnormal ECG Findings 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer 
Number 
Parameter (unit) 
Visit 
Timepoint 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / HH:MM) 
Result 
Abnormal Description 
Clinical Significance 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
XXXX 
PR  (msec) 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
QRS (msec) 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
 
XXXX 
XXXX 
YYYY-MM-DD(XX) / HH:MM 
XXX 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
 
NA = Not Applicable; NCS = Not Clinically Significant; CS = Clinically Significant 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 
Programming Note:  
• The ECG interpretation will be included as a parameter and display in this listing. “Abnormal Description” will be specified if the result if abnormal. 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 53 of 54 
 
Listing XX - Physical Examination 
 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer Number 
Visit 
Timepoint 
Date (d) / Time  
of Physical Examination 
(YYYY-MM-DD (XX) / HH:MM) 
Body System 
Examination 
Finding 
Description of Abnormal Findings  
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
XXXX 
Screening 
XXXX 
YYYY-MM-DD (XX) / HH:MM 
Respiratory Auscultation 
Abnormal NCS 
Abcd 
 
 
 
 
Peripheral Arterial Pulse 
Abnormal CS 
Abcd 
 
 
 
 
…. 
 
 
 
 
 
 
Abdomen 
Abcd  
Abcd 
 
 
 
 
 
 
 
 
Visit 
XXXX 
YYYY-MM-DD (XX) / HH:MM 
Heart Auscultation 
Abcd  
Abcd 
 
 
 
 
Respiratory Auscultation 
Abcd  
Abcd 
 
 
 
 
Peripheral Arterial Pulse 
Abcd  
Abcd 
 
 
 
 
…. 
 
 
 
 
 
 
Abdomen 
Abcd  
Abcd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
NCS = Not Clinically Significant; CS = Clinically Significant; 
                                                                                          
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document status: Mock Listings, v1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
Page 54 of 54 
 
Listing XX – Malaria Clinical Score Results 
Protocol: MMV_MMV533_20_01 
Population: Safety Set 
 
 
Volunteer Number  
Timepoint 
Date (d) / Time of 
Assessment 
(YYYY-MM-DD (XX) / HH:MM) 
Signs/Symptoms 
Result 
Actual Change 
from Baseline 
 
 
 
 
 
 
 
 
 
 
 
Dose Group 
 
 
 
 
 
 
 
XXXX 
 
Pre-inoculation 
YYYY-MM-DD (XX) / HH:MM 
Headache 
 
 
 
 
 
 
: 
 
: 
 
 
 
 
 
 
: 
 
: 
 
 
 
 
 
 
 
 
Total Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
30 hours 
YYYY-MM-DD (XX) / HH:MM 
Headache 
 
 
 
 
 
 
 
 
: 
 
 
 
 
 
 
 
 
: 
 
 
 
 
 
 
 
 
Total Score 
xxx* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes:  Study Day (d): Number of days relative to date of first administration of IMP, where the day of first administration = 1. 
 
Baseline is defined as the last scheduled observation prior to the IMP administration. 
               *Peak Total Score 
 
 
Database Export Date: YYYY-MM-DD                                                                                                      
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM 
 
 
Page X of Y 
 
 


Protocol No: MMV_MMV533_20_01 
Document Status: Mock Figures, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
 
 
 
 
 
 
Page 1 of 5 
 
 
MMV_MMV533_20_01: Mock Figures: Table of Contents 
 
Figure XX: Arithmetic Mean (+SD) Pharmacokinetic Concentration-time Profiles .................................................................................................................................................... 3 
Figure XX: Individual Pharmacokinetic Concentration-time Profiles ............................................................................................................................................................................ 4 
Figure XX: Individual qPCR 18s-time Profiles ................................................................................................................................................................................................................. 5 
Figure XX: Individual RT-PCR pfs25-time Profiles ......................................................................................................................................................................................................... 5 
Figure XX: Individual RT-PCR pfMGET-time Profiles .................................................................................................................................................................................................... 5 
Figure XX: Individual RT-PCR SBP-1-time Profiles ....................................................................................................................................................................................................... 5 
 
 
 


Protocol No: MMV_MMV533_20_01 
Document Status: Mock Figures, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
 
 
 
 
 
 
Page 2 of 5 
 
Notes: 
• 
Unscheduled visits will be excluded from summary tables unless otherwise indicated 
• 
The following footer will be added to all tables: 
Database Export Date: YYYY-MM-DD 
Page X of Y                             
Program: filepath_name (Version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
• 
Footnotes may be added/amended as required 
 
 
 


Protocol No: MMV_MMV533_20_01 
Document Status: Mock Figures, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
 
 
 
 
 
 
Page 3 of 5 
 
Figure XX: Arithmetic Mean (+SD) Pharmacokinetic Concentration-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set  
 
Matrix: Plasma; Analyte: MMV533 
 
 Axis Scale (x-y): Linear-linear 
 
Concentration (units) 
1750  
 
 
 
 
 
 
  
 
 
 
 
 
 
1500  
 
 
 
 
 
 
  
 
 
 
 
 
 
1250  
 
 
 
 
 
 
  
 
 
 
 
 
 
1000  
 
 
 
 
 
 
  
 
 
 
 
 
 
750  
 
 
 
 
 
 
  
 
 
 
 
 
 
500  
 
 
 
 
 
 
  
 
 
 
 
 
 
250  
 
 
 
 
 
 
  
 
 
 
 
 
 
0  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Timepoint 
 
 
 
 Axis Scale (x-y): Linear-log10 
 
log10 Concentration 
(units) 
2000  
 
 
 
 
 
 
  
 
 
 
 
 
 
1000  
 
 
 
 
 
 
  
 
 
 
 
 
 
500  
 
 
 
 
 
 
  
 
 
 
 
 
 
250  
 
 
 
 
 
 
  
 
 
 
 
 
 
0  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Timepoint 
 
 
 
 
Lower Limit of Quantification (XX.X [units]) 
 
 
 
 
Treatment 1 (N = X) 
Treatment 2 (N = X) 
 
 
 … 
Treatment 6 (N = X) 
 
 
Database Export Date: YYYY-MM-DD                                                                                                     
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
 
 
Programming Note:  Repeat for metabolites (MMV022 and MMV023). Replace Plasma to Metabolite 
in Matric and replace MMV533 with MMV022 and MMV023 accordingly. 


Protocol No: MMV_MMV533_20_01 
Document Status: Mock Figures, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
 
 
 
 
 
 
Page 4 of 5 
 
Figure XX: Individual Pharmacokinetic Concentration-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PK Analysis Set  
 
 
Volunteer: xxxxx, Treatment: xxxx mg, Matrix: Plasma; Analyte: MMV533 
 
 Axis Scale (x-y): Linear-linear 
 
Concentration (units) 
1750  
 
 
 
 
 
 
  
 
 
 
 
 
 
1500  
 
 
 
 
 
 
  
 
 
 
 
 
 
1250  
 
 
 
 
 
 
  
 
 
 
 
 
 
1000  
 
 
 
 
 
 
  
 
 
 
 
 
 
750  
 
 
 
 
 
 
  
 
 
 
 
 
 
500  
 
 
 
 
 
 
  
 
 
 
 
 
 
250  
 
 
 
 
 
 
  
 
 
 
 
 
 
0  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Timepoint 
 
 
 
 Axis Scale (x-y): Linear-log10 
 
log10 Concentration 
(units) 
2000  
 
 
 
 
 
 
  
 
 
 
 
 
 
1000  
 
 
 
 
 
 
  
 
 
 
 
 
 
500  
 
 
 
 
 
 
  
 
 
 
 
 
 
250  
 
 
 
 
 
 
  
 
 
 
 
 
 
0  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Timepoint 
 
 
 
 
Database Export Date: YYYY-MM-DD                                                                                                     
Program: filepath_name (version x.x), Output: filepath_name   Created: YYYY-MM-DD HH:MM  
 
 
 
Programming Note:  Repeat for metabolites (MMV022 and MMV023). Replace Plasma to Metabolite 
in Matric and replace MMV533 with MMV022 and MMV023 accordingly. 


Protocol No: MMV_MMV533_20_01 
Document Status: Mock Figures, V1.0 (Final) 
28 November 2022 
 
Southern Star Research – Strictly Confidential 
 
 
 
 
 
 
 
Page 5 of 5 
 
Repeat for the following figures: 
 
Figure XX: Individual qPCR 18s-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
Figure XX: Individual RT-PCR pfs25-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
Figure XX: Individual RT-PCR pfMGET-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
Figure XX: Individual RT-PCR SBP-1-time Profiles 
Protocol: MMV_MMV533_20_01 
Population: PD Analysis Set 
 
 
 
 
 
Programming Note:  The Y-axis should be Geometric Mean of Parasites/ 500μl of Packed RBCs. 
Programming Note:  For Female gametocytemia, the Y-axis should be Copies of transcripts/ 500μl pRBCs. 
 
For at least one of the Pfs25/PFMGET/SBP-1 assay sample replicates there is a cases of one replicate being detected 
and the other being ND or both are ND. In these cases to calculate the geometric mean the ND replicate is replaced 
with the assay LOD/2. Below is the value for LOD/2. 
 
Pfs25 (Female gametocyte): 
 
 
Limit of detection (LoD) 
1080 Copies of transcripts/ 500μl pRBCs 
(3.9 gametocytes/mL) 
LOD/2 = 540 Copies of transcripts/ 500μl pRBCs 
 
PFMGET (Male gametocyte): 
 
 
Limit of detection (LoD) 
340 Copies of transcripts/ 500μl pRBCs 
(26.9 gametocytes/mL) 
LOD/2 = 170 Copies of transcripts/ 500μl pRBCs 
 
SBP-1 (ring stage): 
 
 
Limit of detection (LoD) 
34000 Copies of transcripts/ 500μl pRBCs  
 
(7.38x103 parasites/mL of whole blood) 
 
LOD/2 = 17000 Copies of transcripts/ 500μl pRBCs  
 


MMV_MMV533_20_01_Statistical Analysis Plan
_Final_V1_0_28NOV2022_Package
Final Audit Report
2022-12-01
Created:
2022-11-28 (Australian Eastern Daylight Time (New South Wales))
By:
Ray Lin (rlin@southernstarresearch.com)
Status:
Signed
Transaction ID:
CBJCHBCAABAA7MMchyOum8V0nkH173_YiS-rt83LVmZB
"MMV_MMV533_20_01_Statistical Analysis Plan_Final_V1_0_28
NOV2022_Package" History
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