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MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02281344
First Posted: November 3, 2014
Last Update Posted: May 20, 2016
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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Q-Pharm Pty Limited
Information provided by (Responsible Party):
Medicines for Malaria Venture
  Purpose
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.

Condition Intervention Phase
Malaria, Falciparum Drug: MMV390048 20mg Drug: MMV390048 x mg Drug: MMV390048 y mg Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Proof-of-concept Study to Assess the Effect of MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants.

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • Parasite reduction rate (PRR) following MMV390048 treatment [ Time Frame: up to Day 21 Post-dose ]
    The clearance of malaria parasitemia by Polymerase Chain Reaction (PCR) measurement


Secondary Outcome Measures:
  • MMV390048 Area Under the Plasma Concentration Versus Time Curve (AUC 0-t) up to Day 21 Post-dose [ Time Frame: Up to Day 21 post-dose ]
    pharmacokinetic-pharmacodynamic relationship of MMV390048 on clearance of Plasmodium falciparum parasites from the blood in healthy participants following infection with blood stage parasites

  • MMV390048 Maximum Plasma Concentration (Cmax) [ Time Frame: Up to Day 21 Post-dose ]
    Maximum Plasma Concentration (Cmax) of MMV390048

  • MMV390048 Time to Maximum Plasma Concentration (Tmax) [ Time Frame: up to Day 21 Post-dose ]
    Time to Maximum Plasma Concentration (Tmax) of MMV390048


Enrollment: 6
Study Start Date: October 2014
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Cohort 1 will receive a single, dose of 20mg MMV390048.
Drug: MMV390048 20mg
Supplied as a powder to be prepared as a suspension for oral use
Experimental: Cohort 2
Cohort 2 will receive a single dose of MMV390048. Depending on the data obtained from the 20mg cohort, the dose in Cohort 2 may be adjusted but will not exceed the maximum tolerated dose (or highest achieved dose based on a pre-defined exposure cap) as determined in an ongoing single ascending dose study.
Drug: MMV390048 x mg
Supplied as a powder to be prepared as a suspension for oral use
Experimental: Cohort 3
Cohort 3 will receive a single dose of MMV390048. Depending on the data obtained from the first two cohorts, there may be a 3rd cohort, with the investigated dose of MMV390048 to be determined by the Sponsor and Principal Investigator (PI) and endorsed by the Safety Review Team.
Drug: MMV390048 y mg
Supplied as a powder to be prepared as a suspension for oral use

Detailed Description:

Study using induced blood stage malaria infection to characterize the activity of MMV390048 against early Plasmodium falciparum blood stage infection. There will be two or more cohorts of 8 subjects. In the first cohort a single dose of 20 mg of MMV390048 will be investigated. Depending on the data obtained, the dose in Cohort 2 may be adjusted but will not exceed the maximum tolerated dose (or highest achieved dose based on a predefined exposure cap) as determined in an ongoing single ascending dose study. Each participant will be inoculated on Day 0 with ~1,800 viable parasites of Plasmodium falciparum-infected human erythrocytes intravenously. On an outpatient basis, participants will be monitored daily until positive for presence of malaria parasites. Once positive they will be monitored twice-daily until treatment, for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, participants will be admitted to the study unit and monitored. The threshold for commencement of treatment will be when quantification of all participants is ≥ 1,000 parasites/mL. If the quantification of any participant is ≥ 5,000 parasites/mL, and is accompanied by a clinical symptom score >5, or if clinical or parasitological evidence of malaria occurs in any participant before all participants have reached the treatment threshold (quantification of ≥ 1,000), then treatment of that participant will begin within a 24 h period.

Following treatment with MMV390048, participants will be followed up as inpatients for at least 72 hours to ensure tolerance of the treatment and clinical response, then on an outpatient basis if clinically well for monitoring of safety and clearance of malaria parasites. Compulsory treatment with Riamet® (artemether-lumefantrine) will start on day 16 (±3 days) post study treatment unless required earlier. Early intervention can occur if either poor responses or fast responses are seen following MMV390048 treatment. This is to ensure participant safety and to avoid participant inconvenience if useful data cannot be obtained. Pre-emptive treatment with Riamet® can commence whenever necessary. Participants will be treated with a single dose (45 mg) of primaquine (Primacin™) at the end of their Riamet® treatment if gametocytes are identified, to ensure complete clearance of any gametocytes present.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281344


Locations
Australia, Queensland
Q-Pharm Clinics, Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4006
Sponsors and Collaborators
Medicines for Malaria Venture
Q-Pharm Pty Limited
Investigators
Principal Investigator: James McCarthy, Dr. Q-Pharm Pty Limited
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT02281344     History of Changes
Other Study ID Numbers: QP14C11
First Submitted: October 30, 2014
First Posted: November 3, 2014
Last Update Posted: May 20, 2016
Last Verified: May 2016

Keywords provided by Medicines for Malaria Venture:
induced blood stage malaria infection

Additional relevant MeSH terms:
Infection
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases