MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants
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|ClinicalTrials.gov Identifier: NCT02281344|
Recruitment Status : Terminated (Inconsistent and unpredictable exposures were observed. Drug needed to be reformulated.)
First Posted : November 2, 2014
Results First Posted : June 9, 2020
Last Update Posted : June 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Malaria, Falciparum||Drug: MMV390048 20mg||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|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.|
|Actual Study Start Date :||October 2014|
|Actual Primary Completion Date :||December 19, 2014|
|Actual Study Completion Date :||December 19, 2014|
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
- MMV390048 Area Under the Plasma Concentration Versus Time Curve (AUClast) up to Day 21 Post-dose [ Time Frame: 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. ]
Pharmacokinetic-pharmacodynamic relationship of MMV390048 on clearance of Plasmodium falciparum parasites from the blood in healthy participants following infection with blood stage parasites.
The area under the plasma concentration time curve from time zero to the last measured time point.
- Parasite Reduction Rate (PRR) Following MMV390048 Treatment [ Time Frame: From dosing up to Day 21 Post-dose ]The clearance of malaria parasitemia by Polymerase Chain Reaction (PCR) measurement.
- MMV390048 Maximum Plasma Concentration (Cmax) [ Time Frame: 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. ]Maximum Plasma Concentration (Cmax) of MMV390048
- MMV390048 Time to Maximum Plasma Concentration (Tmax) [ Time Frame: From dosing up to Day 21 Post-dose ]Time to Maximum Plasma Concentration (Tmax) of MMV390048
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
|Q-Pharm Clinics, Royal Brisbane and Women's Hospital|
|Brisbane, Queensland, Australia, 4006|
|Principal Investigator:||James McCarthy, Dr.||Q-Pharm Pty Limited|