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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04323306




Registration number
NCT04323306
Ethics application status
Date submitted
12/03/2020
Date registered
26/03/2020
Date last updated
24/09/2020

Titles & IDs
Public title
A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of a Single Doses of MMV533.
Scientific title
A Two-part, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of Ascending Single Doses of MMV533, Including a Pilot Food Evaluation in Healthy Participants.
Secondary ID [1] 0 0
MMV-MMV533_19_01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MMV688533

Active Comparator: Cohort 1 SAD - 5 mg MMV533 with single ascending dose

Active Comparator: Cohort 2 SAD - Single ascending dose to be determined after SRC review of previous cohort.

Active Comparator: Cohort 3 SAD - Single ascending dose to be determined after SRC review of previous cohort.

Active Comparator: Cohort 4 SAD - Single ascending dose to be determined after SRC review of previous cohort.

Active Comparator: Cohort 5 SAD - Single ascending dose to be determined after SRC review of previous cohort.

Active Comparator: Cohort 6 SAD - Single ascending dose to be determined after SRC review of previous cohort.

Active Comparator: Cohort 7 SAD - Single ascending dose to be determined determine after SRT review of previous cohort. Dose will not exceed 400 mg.

Active Comparator: Part 2: Food Effect - Open label, 2-period cross-over, randomized, pilot food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV533 determined to be safe in Part 1.


Treatment: Drugs: MMV688533
Investigational medicinal product

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical laboratory evaluations; haematology - Incidence of abnormal blood work results
Timepoint [1] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [2] 0 0
Clinical laboratory evaluations; biochemistry - Incidence of abnormal blood work results
Timepoint [2] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [3] 0 0
Clinical laboratory evaluations; urinalysis - Incidence of abnormal blood work urinalysis
Timepoint [3] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [4] 0 0
Number of Participants with changes in vital signs; Systolic and Diastolic Blood Pressure - Incidence of changes in Systolic and Diastolic Blood Pressure
Timepoint [4] 0 0
From baseline until 28 days after IMP/placebo administration
Primary outcome [5] 0 0
Number of Participants with changes in vital signs; heart rate supine and resting - Incidence of changes in vital signs; heart rate supine and resting
Timepoint [5] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [6] 0 0
Number of Participants with changes in vital signs; respiratory rate - Incidence of changes in vital signs; respiratory rate
Timepoint [6] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [7] 0 0
Number of Participants with changes in vital signs; body temperature - Incidence of changes in vital signs; body temperature
Timepoint [7] 0 0
baseline until 28 days after IMP/placebo administration
Primary outcome [8] 0 0
Number of Participants with ECG changes - triplicate ECGs with central reading from Day 1 predose and up to and including 96 hours post IMP administration. - Overall assessment as normal, abnormal not clinically significant, or abnormal clinically significant.
Timepoint [8] 0 0
Day 1 pre-dose up to and including 96 hours post-IMP/placebo administration
Primary outcome [9] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 - Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Timepoint [9] 0 0
baseline until 28 days after IMP/placebo administration
Secondary outcome [1] 0 0
Pharmacokinetics of MMV533 - Cmax - Cmax
Timepoint [1] 0 0
Pre-dose until 28 days after IMP/placebo administration
Secondary outcome [2] 0 0
Effect of a high-fat meal on the PK of MMV533 - Participants will be assess while fasted and fed a high fat meal.
Timepoint [2] 0 0
Baseline to Day 42
Secondary outcome [3] 0 0
Pharmacokinetics of MMV533 - Tmax - Tmax
Timepoint [3] 0 0
Pre-dose until 28 days after IMP/placebo administration
Secondary outcome [4] 0 0
Pharmacokinetics of MMV533 - AUClast - AUClast
Timepoint [4] 0 0
Pre-dose until 28 days after IMP/placebo administration
Secondary outcome [5] 0 0
Pharmacokinetics of MMV533 - AUCinf - AUCinf
Timepoint [5] 0 0
Pre-dose until 28 days after IMP/placebo administration

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Males and females (of childbearing and non-childbearing potential) , between 18 and 55
years of age, inclusive. Women of childbearing potential (WOCBP) must use highly
effective methods of birth control (see Inclusion #3).

2. Females of non-childbearing potential:

1. 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)

2. Premenopausal with irreversible surgical sterilization by hysterectomy and/or
bilateral oophorectomy or salpingectomy at least 6 months before screening (as
determined by participant medical history)

3. Women of childbearing potential that have or may have male sexual partners during the
course of the study must agree to the use of a double method of contraception of a
highly effective method of birth control combined with a barrier contraceptive
(condom) when appropriate from screening visit to until 60 days after the last dose of
IMP (covering a full menstrual cycle of 30 days starting after 5 half-lives of last
dose of IMP. This duration is based on the predicted half-life of IMP, and may be
amended once the actual half-life is calculated during this study). Note: Highly
effective birth control methods include: combined (oestrogen and progestogen
containing) oral/intravaginal/transdermal hormonal contraception associated with
inhibition of ovulation, progestogen-only oral/injectable/implantable hormonal
contraception associated with inhibition of ovulation, intrauterine device (IUD),
intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised
partner, or sexual abstinence or same sex relationship.

4. Male participants who have, or may have female sexual partners during the course of
the study must agree to use a double method of contraception including condom plus
diaphragm, or condom plus stable insertable (implant or IUD), injectable, transdermal
or combination oral contraceptive by the female partner, from the time of informed
consent through to 90 days after the last dose of the IMP (covering a full
spermatogenesis cycle of 60 days starting after 5 half-lives of last dose of IMP. This
duration is based on the predicted half-life of IMP, and may be amended once the
actual half-life is calculated during this study).

Abstinent male participants must agree to start a double method if they begin a sexual
relationship with a female during the trial, and through to 90 days after the last
dose of the IMP. Male participants with female partners that are surgically sterile or
post-menopausal (defined as being amenorrhoeic for at least 12 months without an
alternative medical cause), or male participants 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. Male
participants must also agree not to donate sperm up to 3 months after dosing with the
IMP.

5. Total body weight greater than or equal to 50 kg, and body mass index (BMI) between 18
and 32 kg/m2 inclusive.

6. Certified as healthy by a comprehensive clinical assessment (detailed medical history
and complete physical examination).

7. Normal vital signs after 5 minutes resting in supine position:

- Systolic blood pressure (SBP) - 90-140 mmHg,

- Diastolic blood pressure (DBP) - 40-90 mmHg,

- Heart rate (HR) 40-100 bpm.

8. Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine
position in the following ranges for both males and females: QT = 500 msec, QTcF =450
msec, QTcB =450 msec, and PR interval =210 msec; and normal ECG tracing unless the
Principal Investigator or delegate considers an ECG tracing abnormality to be not
clinically significant.

9. Having given written informed consent prior to undertaking any study-related
procedure.

10. Available for the duration of the study and for 2 weeks following the End of Study
visit.

11. 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.

12. Fluent in English and able to understand and comply with written and verbal
protocol-related requirements.

13. Willing to defer blood donations to a blood service for a minimum of 6 months after
the End of Study visit.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria

1. Haematology, biochemistry or urinalysis results that are abnormal/outside of
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 the Sponsor-approved clinically acceptable laboratory
ranges in Appendix 1 of the protocol.

NOTE: Participants 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 of the protocol of .

2. Positive serum pregnancy test at screening, positive urine pregnancy test upon
admission or at other timepoints as specified by schedule of assessments.

3. Male participants with a female partner(s) who is (are) pregnant or lactating from the
time of the administration of study medication.

4. Any history or presence of clinically relevant cardiovascular, broncho-pulmonary,
gastrointestinal, hepatic/ gallbladder*/ bile duct, renal, metabolic, haematological,
neurological, musculoskeletal/rheumatologic, systemic, ocular, gynaecologic (if
female), or infectious disease, or signs of acute illness. *including medical history
of asymptomatic gallbladder stones.

5. Any gastrointestinal surgery or any condition or disease that could affect drug
absorption, distribution or excretion (eg, gastrectomy, cholecystectomy, diarrhoea).

6. Severe recurring headaches (cluster or migrainous headaches) requiring prescription
medication/s. History of recurrent nausea and/or vomiting (for vomiting only: more
than twice a month).

7. Participation in any research study involving blood sampling (more than 450 mL/unit of
blood) or blood donation during the 8 weeks prior to IMP administration (Parts 1 and
2).

8. 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
(confirmed on two consecutive readings), irrespective of the decrease in blood
pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood
pressure =20 mmHg within 2-3 min when changing from supine to standing position.

9. 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. Participants 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.

10. History of convulsion (including drug or vaccine-induced episodes). A medical history
of a single febrile convulsion during childhood is not an exclusion criterion.

11. History of substance use disorder(s) within 5 years of screening, including alcohol
consumption of more than 40g/4 units/4 standard drinks per day or any prior
intravenous use of an illicit substance.

12. Smoked >1 pack of cigarettes per day for >10 years, or who currently (within 14 days
prior to IMP administration (Parts 1 and 2) smokes >5 cigarettes per day.

13. Any medication (including herbal such as St John´s Wort, vitamin supplements and over
the counter [OTC]) within 5 half-lives prior to IMP administration (Parts 1 and 2),
except occasional intakes (for acute pain) of ibuprofen at doses up to 1.8g/day,
paracetamol at doses up to 4g/day, acetylsalicylic acid (300 to 650 mg orally every 4
to 6 hours as needed Maximum dose: 4g in 24 hours), diclofenac (diclofenac potassium
liquid-filled capsules: 25mg orally 4 times a day; diclofenac free acid capsules: 18
or 35 mg orally 3 times a day; diclofenac potassium immediate-release tablets: 50mg
orally 3 times a day [initial dose of 100mg orally followed by 50mg oral doses
acceptable if required for better relief]) and contraceptives.

14. 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.

15. Any individual in the exclusion period of a previous study according to applicable
regulations.

16. Any individual who cannot be contacted in case of emergency.

17. 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.

18. Any individual without a good peripheral venous access.

19. Participation in any investigational product study within the 12 weeks preceding IMP
administration (Parts 1 and 2) or 5 times the half-life of the Investigational
product, whichever is longer.

20. 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).

21. Positive urine drug test at screening or prior to IMP dosing. Any drug from the list
of drugs tested unless there is an acceptable explanation to the Principal
Investigator or delegate (eg, participant has stated in advance that they consumed a
prescription of over the counter product which contained the detected drug) and/or the
participant has a negative urine drug screen on retest. Any participant tested
positive for paracetamol at screening may still be eligible for study participation,
at the Principal Investigator's or delegate's discretion.

22. Positive alcohol screen at screening or prior to IMP dosing.

23. Any consumption of citrus fruits (grapefruit, Seville oranges) or their juices within
5 days prior to IMP administration.

24. Use of antidepressant medication in the past 12 months prior to IMP administration in
Part 1 and 2.

25. Individuals with history of schizophrenia, bipolar disorder psychoses, disorders
requiring lithium, attempted or planned suicide, or any other severe (disabling)
chronic psychiatric diagnosis including generalised anxiety and obsessivecompulsive
disorders.

26. Individuals who have been hospitalised within five years prior to enrolment for either
a psychiatric illness or due to danger to self or others.

27. History of an episode of mild/moderate depression lasting more than 6 months that
required pharmacological therapy and/or psychotherapy within the last 5 years; or any
episode of major depression. The Beck Depression Inventory (BDIII) will be used as a
validated tool for the assessment of depression at screening. In addition to the
conditions listed above, individuals with a score of 20 or more on the BDI-II 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. These individuals will be referred to a general
practitioner or medical specialist as appropriate. Individuals with a BDI-II score of
17 to 19 may be enrolled at the discretion of an 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 individual or to
the execution of the trial and interpretation of the data gathered.

28. 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.

29. Any vaccination within 28 days of screening.

30. Any medical condition that in the opinion of the Principal Investigator or delegate
would jeopardize the individual's involvement in the study.

Specific to Part 2 only:

31. Any individual who, in the opinion of the Principal Investigator or delegate, would be
unwilling or unable to consume the pre-dose test meal during the fed arm.

32. Individuals with food intolerance or food allergy are excluded. Vegetarian individuals
must be excluded, unless they agree to eat a full diet during the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network Corporate - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Medicines for Malaria Venture
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Nucleus Network Ltd
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Southern Star Research Pty Ltd.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1, single -centre study in 2 parts. The study designs for each part are well
established for first-in-human studies and are appropriate to assess safety, tolerability and
preliminary pharmacokinetics.
Trial website
https://clinicaltrials.gov/show/NCT04323306
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason Lickliter, MD
Address 0 0
Nucleus Network Corporate
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anne Mwangi, BSc
Address 0 0
Country 0 0
Phone 0 0
00254735441318
Fax 0 0
Email 0 0
mwangia-consultants@mmv.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04323306