MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants
Condition: Malaria, Falciparum
MeSH terms: Infections; Malaria; Malaria, Falciparum
Intervention: MMV390048 20mg
Intervention description: Supplied as a powder to be prepared as a suspension for oral use
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: induced blood stage malaria infection

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.
    

Eligibility criteria:

        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

        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