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NCT02880241

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

Terminated Phase 2 Results posted Last updated 9 December 2021
What this trial tests

Phase 2 trial testing MMV390048 in Malaria in 8 participants. Terminated before completion.

Timeline
20 October 2017
Primary endpoint
1 January 2018
24 September 2018

Quick facts

Lead sponsorMedicines for Malaria Venture
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment8
Start date20 October 2017
Primary completion1 January 2018
Estimated completion24 September 2018
Sites2 locations across Ethiopia

Drugs / interventions tested

Conditions studied

Sponsor

Medicines for Malaria Venture — full company profile →

Who can join

Adults 18 to 55, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Crude Adequate Clinical and Parasitological Response (ACPR) for P. Vivax Primary · On Day 14 post-dose

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

GroupValue95% CI
Cohort 1A - P. Vivax Malaria8

Adverse events — posted to ClinicalTrials.gov

Time frame: From IMP administration (Day 0) to End of Study (Day 35). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1B - P. Falciparum Malaria
Serious: 0
Deaths: 0
Cohort 1A - P. Vivax Malaria
Serious: 0/8 (0%)
Deaths: 0/8
Cohort 2A - P. Vivax Malaria
Serious: 0
Deaths: 0
Cohort 2B - P. Falciparum Malaria
Serious: 0
Deaths: 0
Cohort 3A - P. Vivax Malaria
Serious: 0
Deaths: 0
Cohort 3B - P. Falciparum Malaria
Serious: 0
Deaths: 0
Other adverse events (20 terms — click to expand)

ReactionSystemCohort 1B - P. Falciparum …Cohort 1A - P. Vivax MalariaCohort 2A - P. Vivax MalariaCohort 2B - P. Falciparum …Cohort 3A - P. Vivax MalariaCohort 3B - P. Falciparum …
Abdominal discomfortGastrointestinal disorders
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
NauseaGastrointestinal disorders
Oral discomfortGastrointestinal disorders
VomitingGastrointestinal disorders
AscariasisInfections and infestations
CarbuncleInfections and infestations
Hookworm infectionInfections and infestations
P.falciparum infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Sinus TachycardiaCardiac disorders
FatigueGeneral disorders
Haemoglobin decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Urinary Tract DiscomfortRenal and urinary disorders

Data from ClinicalTrials.gov NCT02880241 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Drugs in Development for Malaria.
    Ashley EA, Phyo AP. · · 2018 · cited 123× · PMID 29802605 · DOI 10.1007/s40265-018-0911-9
  2. Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel <i>Plasmodium</i> Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers.
    Sinxadi P, Donini C, Johnstone H, Langdon G, et al · · 2020 · cited 53× · PMID 31932368 · DOI 10.1128/aac.01896-19
  3. A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048.
    McCarthy JS, Donini C, Chalon S, Woodford J, et al · · 2020 · cited 46× · PMID 32239164 · DOI 10.1093/cid/ciaa368
  4. Recent updates in the discovery and development of novel antimalarial drug candidates.
    Okombo J, Chibale K, Chibale K. · · 2018 · cited 38× · PMID 30108934 · DOI 10.1039/c7md00637c
  5. Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.
    Erhunse N, Sahal D. · · 2021 · cited 17× · PMID 34765267 · DOI 10.1016/j.jpha.2020.07.005
  6. Scoping Review of Antimalarial Drug Candidates in Phase I and II Drug Development.
    Abd-Rahman AN, Zaloumis S, McCarthy JS, Simpson JA, et al · · 2022 · cited 15× · PMID 34843390 · DOI 10.1128/aac.01659-21
  7. Efficacy, Safety, Tolerability, and Pharmacokinetics of MMV390048 in Acute Uncomplicated Malaria.
    Mohammed R, Asres MS, Gudina EK, Adissu W, et al · · 2023 · cited 9× · PMID 36509063 · DOI 10.4269/ajtmh.22-0567
  8. An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.
    Moolman C, Sluis RV, Beteck RM, Legoabe LJ. · · 2020 · cited 8× · PMID 33171706 · DOI 10.3390/molecules25215182

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