MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants

NCT02281344 | Terminated Phase 1 Results DMC

• 1 other identifier: QP14C11
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Falciparum

Keywords

induced blood stage malaria infection

Outcome Measures

Primary Outcomes (1)

• MMV390048 Area Under the Plasma Concentration Versus Time Curve (AUClast) 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. The area under the plasma concentration time curve from time zero to the last measured time point.

  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 Outcomes (3)

• Parasite Reduction Rate (PRR) Following MMV390048 Treatment

  From dosing up to Day 21 Post-dose

• MMV390048 Maximum Plasma Concentration (Cmax)

  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.

• MMV390048 Time to Maximum Plasma Concentration (Tmax)

  From dosing up to Day 21 Post-dose

Study Arms (1)

Cohort 1

EXPERIMENTAL

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

Drug: MMV390048 20mg

Interventions

MMV390048 20mg DRUG

Supplied as a powder to be prepared as a suspension for oral use

Cohort 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Q-Pharm Pty Limited: collaborator

Study Sites (1)

Q-Pharm Clinics, Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4006, Australia

Location

Related Publications (2)

• Sinxadi P, Donini C, Johnstone H, Langdon G, Wiesner L, Allen E, Duparc S, Chalon S, McCarthy JS, Lorch U, Chibale K, Mohrle J, Barnes KI. Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01896-19. doi: 10.1128/AAC.01896-19. Print 2020 Mar 24.

  PMID: 31932368 DERIVED

• Burel JG, Apte SH, McCarthy JS, Doolan DL. Plasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential. PLoS Negl Trop Dis. 2016 Dec 8;10(12):e0005031. doi: 10.1371/journal.pntd.0005031. eCollection 2016 Dec.

  PMID: 27930660 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

MMV390048

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Limitations and Caveats

Dose escalation was planned for more than 1 cohort, but due to inconsistent pharmacokinetic profiles the study was terminated.

Results Point of Contact

• Title: Dr Cristina Donini
• Organization: Medicines for Malaria Venture

doninic@mmv.org

+41 22 555 0312

Study Officials

• James McCarthy, Dr.

  Q-Pharm Pty Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 3, 2014
• Study Start: October 1, 2014
• Primary Completion: December 19, 2014
• Study Completion: December 19, 2014
• Last Updated: June 9, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-05

Locations

AU (1)