Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02281344




Registration number
NCT02281344
Ethics application status
Date submitted
30/10/2014
Date registered
2/11/2014
Date last updated
9/06/2020

Titles & IDs
Public title
MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants
Scientific title
A Proof-of-concept Study to Assess the Effect of MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants.
Secondary ID [1] 0 0
QP14C11
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MMV390048 20mg

Experimental: Cohort 1 - Cohort 1 will receive a single dose of 20mg MMV390048.


Treatment: Drugs: MMV390048 20mg
Supplied as a powder to be prepared as a suspension for oral use
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MMV390048 Area Under the Plasma Concentration Versus Time Curve (AUClast) up to Day 21 Post-dose
Timepoint [1] 0 0
At pre-dose, and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 (D1), 30, 36, 48 (D2), 72 (D3), and 144 hours (D6) and Days 8, 10, 14, 18 and D21.
Secondary outcome [1] 0 0
Parasite Reduction Rate (PRR) Following MMV390048 Treatment
Timepoint [1] 0 0
From dosing up to Day 21 Post-dose
Secondary outcome [2] 0 0
MMV390048 Maximum Plasma Concentration (Cmax)
Timepoint [2] 0 0
At pre-dose, and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 (D1), 30, 36, 48 (D2), 72 (D3), and 144 hours (D6) and Days 8, 10, 14, 18 and D21.
Secondary outcome [3] 0 0
MMV390048 Time to Maximum Plasma Concentration (Tmax)
Timepoint [3] 0 0
From dosing up to Day 21 Post-dose

Eligibility
Key inclusion criteria
- Participants who do not live alone from Day 0 until at least the end of the
antimalarial drug treatment, and are contactable and available for the duration of the
trial (=4 months)

- Body weight =50kg, body mass index between 18.0 and 32.0 kg/m2, inclusive

- Healthy by clinical assessment

- Normal vital signs

- Normal 12-lead electrocardiogram

- Lab tests in normal range

- Agrees to use a double barrier method of contraception including condom plus diaphragm
or condom plus intrauterine device or condom plus stable oral / transdermal /
injectable hormonal contraceptive by female partner for =14 days prior to the first
dose of study drug until 90 days after the last dose

- Written informed consent before any study procedure
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- History of malaria or participation in a previous malaria challenge study

- Must not have travelled to or lived >2 weeks in a malaria-endemic area in past 12
months nor plan to travel to one during study

- Evidence of increased cardiovascular disease risk

- History of splenectomy

- Presence / history of drug hypersensitivity, or allergic disease diagnosed and treated
or history of a severe allergic reaction, anaphylaxis or convulsions following any
vaccination or infusion

- Presence of current / suspected serious chronic diseases such as cardiac or autoimmune
disease, diabetes, progressive neurological disease, severe malnutrition, acute or
progressive hepatic or renal disease, psoriasis, rheumatoid arthritis, asthma,
epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable
skin cancers such as basal cell and squamous cell carcinoma, schizophrenia, bi-polar
disease, or other severe (disabling) chronic psychiatric diagnosis

- History of photosensitivity

- History of schizophrenia, bi-polar disease, or other severe (disabling) chronic
psychiatric diagnosis, including depression or receiving psychiatric drugs or
hospitalized in past 5 yrs for psychiatric illness, history of suicide attempt or
confinement for danger to self/others

- Frequent headache and/or migraine, recurrent nausea, and/or vomiting (=2 / month)

- Acute infectious disease/fever in 5 days pre-inoculation with malaria parasites

- Acute illness in 4 weeks pre-screening which may compromise subject safety

- Any significant intercurrent disease, in particular liver, renal, cardiac, pulmonary,
neurologic, rheumatologic, or autoimmune disease by history, physical exam or lab test

- Clinically significant disease or any condition that might affect drug absorption
distribution or excretion

- Participation in any investigational study in last 12 weeks

- Any blood sampling/donation in last 8 weeks

- Unwilling to defer blood donation for 6 months

- Any blood donation, in 1 month before inclusion.

- Medical requirement for intravenous immunoglobulin or blood transfusion

- Ever had a blood transfusion

- Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or
asymptomatic postural hypotension

- History or presence of alcohol abuse (=40g per day) or drug habituation, or any prior
intravenous use of an illicit substance

- Smoking =5 cigarettes or equivalent /day and unable to stop smoking during confinement
period

- Poppy seeds in 24h pre-screening

- Excessive consumption of xanthine bases, including red bull, chocolate

- Any medication (including St John's Wort) in 14 days pre-study or within 5 times the
medication half-life if longer

- Vaccination in the last 28 days

- Any corticosteroids, anti-inflammatory, immunomodulators or anticoagulants. Any
currently or previous immunosuppressive therapy, including systemic steroids including
adrenocorticotrophic hormone or inhaled steroids in dosages associated with
hypothalamic-pituitary-adrenal axis suppression or chronic use of inhaled high potency
corticosteroids

- Recent or current systemic therapy with an antibiotic / potential antimalarial

- Likely to be noncompliant, or unable to cooperate

- Not contactable in case of emergency throughout and for 2 weeks after end of study

- Staff directly involved in study conduct

- Without good peripheral venous access

- Positive for: hepatitis B surface antigen, anti-hepatitis B core antibodies,
anti-hepatitis C virus antibodies, or anti-human immunodeficiency virus 1/2 antibodies

- glucose-6-phosphate dehydrogenase deficiency

- Positive urine drug screen or alcohol urine or breath test

- Cardiac/QT risk: Known pre-existing prolongation of the QTcB/QTcF interval considered
clinically significant. Family history of sudden death or of congenital prolongation
of the corrected QT interval interval or known congenital prolongation of the
corrected QT interval or any clinical condition known to prolong the corrected QT
interval interval. History of symptomatic cardiac arrhythmias or with clinically
relevant bradycardia. Electrolyte disturbances, particularly hypokalaemia,
hypocalcaemia or hypomagnesaemia. Clinically relevant 12-lead electrocardiogram
abnormality at screening or which will interfere with the analysis, or history of
clinically significant abnormalities

- Known hypersensitivity to MMV390048 or any of its excipients or 4-aminoquinolines,
artemether or other artemisinin derivatives, lumefantrine, or other arylaminoalcohols

- Unwillingness to abstain from citrus (grapefruit, Seville orange, etc.) or juice, as
well as quinine containing foods/beverages for the study period

- Lactose intolerance

- Unwilling to restrict exposure to direct sunlight during the study. Must use
sunglasses and sunblock for the study period

Study design
Purpose of the study
Basic Science
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/12/2014
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Clinics, Royal Brisbane and Women's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Medicines for Malaria Venture
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Q-Pharm Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
A single-centre, open-label, study using induced blood stage malaria infection to
characterize the activity of MMV390048 against early Plasmodium falciparum blood stage
infection.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02281344
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James McCarthy, Dr.
Address 0 0
Q-Pharm Pty Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02281344