MMV390048 POC in Patients With P. Vivax and P. Falciparum Malaria

NCT02880241 | Terminated Phase 2 Results DMC

• 1 other identifier: MMV_MMV390048_16_02
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

The present proof-of-concept Phase IIa study aims to confirm, in patients, the observed activity of MMV390048 against P. falciparum in pre-clinical models and the human Induced Blood-Stage Malaria (IBSM) challenge model, and to determine the activity against P. vivax malaria in patients, both over 14 and 28 days. Additional aims are to characterise the safety of MMV390048 in patients. Patient safety will be monitored for up to 35 days post-dose including pharmacokinetic assessments. The study will investigate descending single doses of MMV390048 in response to results obtained in the first cohort/dose in each malaria sub-type. The results of this trial will identify active, well-tolerated doses for investigation in combination with a partner drug within a Phase IIb clinical trial.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Crude Adequate Clinical and Parasitological Response (ACPR) for P. Vivax

  The absence of parasitaemia (thick smear) on Day 14, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure. Parasitaemia was defined as a P. vivax asexual forms count \>0

  On Day 14 post-dose

• For P. Falciparum: PCR-adjusted Crude Adequate Clinical and Parasitological Response (ACPR)

  Number of participants meeting PCR-adjusted Crude Adequate Clinical and Parasitological Response (ACPR)

  On Day 14 post-dose

Study Arms (6)

Cohort 1A - P. vivax malaria

EXPERIMENTAL

A single oral dose of up to 120mg MMV390048

Drug: MMV390048

Cohort 1B - P. falciparum malaria

EXPERIMENTAL

A single oral dose of up to 120mg MMV390048

Drug: MMV390048

Cohort 2A - P. vivax malaria

EXPERIMENTAL

A single oral dose (to be determined) of MMV390048

Drug: MMV390048

Cohort 2B - P. falciparum malaria

EXPERIMENTAL

A single oral dose (to be determined) of MMV390048

Drug: MMV390048

Cohort 3A - P. vivax malaria

EXPERIMENTAL

A single oral dose (to be determined) of MMV390048

Drug: MMV390048

Cohort 3B - P. falciparum malaria

EXPERIMENTAL

A single oral dose (to be determined) of MMV390048

Drug: MMV390048

Interventions

MMV390048 DRUG

Tablets of 20mg each

Cohort 1A - P. vivax malaria; Cohort 1B - P. falciparum malaria; Cohort 2A - P. vivax malaria; Cohort 2B - P. falciparum malaria; Cohort 3A - P. vivax malaria; Cohort 3B - P. falciparum malaria

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Body weight between 40 kg and 90 kg inclusive
• Presence of P. vivax or P. falciparum monoinfection confirmed by:
• Fever, as defined by axillary temperature ≥37.5°C or oral/rectal/tympanic temperature ≥38°C, or history of fever in the previous 48 hours for P. vivax and 24 hours for P. falciparum and,
• Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite count/µL blood
• Written informed consent provided by the patient in accordance with local practice. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
• Ability to swallow oral medication
• The patient is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned
• Willing to be hospitalized for at least 72 hours or until malarial parasites are not detected by microscopy on 2 consecutive occasions whichever comes later and return to clinic for all follow-up visits
• Women must be of non-childbearing potential (WNCBP) as per one of the following definitions:
• postmenopausal defined as having age-appropriate, natural (spontaneous) amenorrhea for at least 12 months prior to screening in the absence of an alternative medical cause for the amenorrhea, or
• premenopausal with irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy or salpingectomy at least 6 months prior to screening (as determined by subject medical history)
• Sexually active men must agree to comply with strict appropriate contraception rules (barrier contraception, e.g. condom) or complete abstinence when this is in line with the preferred and usual lifestyle of the patient. The contraception coverage in this situation should ensure full elimination of MMV390048, i.e. until 120 days after MMV390048 administration to the enrolled male patient (covering a full sperm cycle of 90 days starting after 5 x t½ of the drug). Abstinent patients must agree to use the above-mentioned contraceptive methods if they start sexual relationships during the study, and to continue these methods until 120 days after study medication.

You may not qualify if:

• Patients with signs and symptoms of severe / complicated malaria according to the World Health Organisation Criteria 2012
• Mixed Plasmodium infection
• Women who are nursing (lactating)
• Presence of other serious or chronic clinical condition requiring hospitalisation
• Severe malnutrition (defined as a body mass index \[BMI\] of less than 16 kg/m2 as per local guidelines)
• Presence of concurrent febrile illness (e.g. typhoid fever)
• Known history or evidence of clinically significant:
• cardiovascular disease (including arrhythmia, QTcF interval \>450 msec, personal or family history of long QT syndrome, PR interval \>200msec; any relevant intra-ventricular heart block \[QRS \>120msec\]),
• respiratory conditions (including active tuberculosis),
• history of jaundice or other hepatic dysfunction,
• renal insufficiency,
• gastrointestinal disorder, or any condition that may affect absorption of the study medication (e.g. vomiting or diarrhea),
• immunological disorders (including known pre-existing HIV infection),
• endocrine disorders (including any type of diabetes mellitus whether controlled or not, diabetes insipidus, uncontrolled hypo- or hyperthyroidism, endocrine reproductive disorders not requiring concurrent medication, disorders of adrenal function),
• infectious conditions (other than minor skin or soft tissue infections or confirmed minor lower urinary tract infection),

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• University of Gondar: collaborator
• Jimma University: collaborator

Study Sites (2)

University of Gondar Hospital/Maksegnit Health Centre

Gonder, Amhara, 6200, Ethiopia

Location

Jimma University Referral Hospital/Agaro District Hospital

Jimma, Oromiya, Ethiopia

Location

Related Publications (1)

• Mohammed R, Asres MS, Gudina EK, Adissu W, Johnstone H, Marrast AC, Donini C, Duparc S, Yilma D. Efficacy, Safety, Tolerability, and Pharmacokinetics of MMV390048 in Acute Uncomplicated Malaria. Am J Trop Med Hyg. 2022 Dec 5;108(1):81-84. doi: 10.4269/ajtmh.22-0567. Print 2023 Jan 11.

  PMID: 36509063 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

MMV390048

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Stephan Duparc, Chief Medical Officer
• Organization: Medicines for Malaria Venture (MMV)

duparcs@mmv.org

+41 22 555 0351

Study Officials

• Esayas Gudina, MD

  Jimma University

  PRINCIPAL INVESTIGATOR

• Mezgebu Silamsaw, MD

  University of Gondar

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: October 20, 2017
• Primary Completion: January 1, 2018
• Study Completion: September 24, 2018
• Last Updated: December 9, 2021
• Results First Posted: December 9, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

ET (2)