Malaria
Conditions
Interventions
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are = 12 and = 55 years of age (= 18 and = 55 years of age for Part A) at the time of signing the informed consent. 2. Microscopic confirmation of acute uncomplicated P. falciparum using Giemsa-stained thick and thin film. 3. P. falciparum parasitemia of 1,000 to 50,000 asexual parasites/µL of blood in Part A and P. falciparum parasitemia of > 1,000 to = 150,000 asexual parasites/µL of blood in Part B. 4. Axillary temperature = 37.5ºC or tympanic temperature = 38.0ºC (use as per COVID-19 protocols at the site [only at Screening]), or history of fever during the previous 24 hours (at least documented verbally). 5. Have a body weight = 24 kg. 6. “All sexes allowed” The Investigator confirms that each participant agrees to use appropriate contraception and barriers, if applicable. The contraception (in line with local regulations), barrier, and pregnancy testing requirements are below. Male study participants: Agree to the following during the study intervention period and for = 120 days after the last dose of study intervention: a. Refrain from donating fresh unwashed semen PLUS, either: b. Abstain from intercourse with a WOCBP. OR c. Use a male condom: When having sexual intercourse with a WOCBP, who is not currently pregnant, and instruct her to use a highly effective contraceptive method with a failure rate of <1% per year, as described in protocol Appendix 3. Female study participants: - Is not breastfeeding. - Is not pregnant (i.e., has a negative serum pregnancy test, as required by local regulations, within 24 hours before the first dose of study intervention). - Is not a WOCBP. - If a WOCBP, uses a highly effective contraceptive method (i.e., with a failure rate of <1% per year), preferably with low user dependency, as described in protocol Appendix 3. 7. Capable of giving signed informed consent, as per protocol Appendix 2, which includes compliance with the requirements and restrictions listed in the ICF and protocol
Exclusion criteria
Exclusion criteria: 1. Mixed Plasmodium infections as per thin film microscopy results. 2. Signs and symptoms of severe malaria according to WHO 2021 criteria (WHO 2021). 3. Known liver abnormalities, liver cirrhosis (compensated or decompensated), known active or history of hepatitis B or C (testing not required), underlying hepatic injury or known severe liver disease, known gallbladder or bile duct disease, acute or chronic pancreatitis, or severe malnutrition. 4. Known history or evidence of clinically significant disorders such as, cardiovascular, respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including known HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions, or other abnormality (including head trauma). 5. Previous treatment with pyronaridine as part of a combination therapy during the last 3 months. 6. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected PD effect has returned to Baseline, whichever is longer. 7. Prior antimalarial therapy or antibiotics with antimalarial activity within a minimum of their 5 plasma half-lives (or within 4 weeks of Screening if half-life is unknown). 8. Patients taking medications prohibited by the protocol. 9. Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance during the last 3 months. 10. Participation in any clinical study within 3 months or 5 half lives prior to Screening or during participation in this study. 11-19 Diagnostic assessments including serum creatinine levels, AST and/or ALT, TB, QTc interval, electrolyte balance, moderate to severe anaemia, severe malnutrition, severe vomiting. See Protocol for details on exclusion criteria 11-19. 20. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, M5717, and/or artesunate. 21 Known history or current substance abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A Primary Objective - To evaluate the safety and tolerability of the M5717-pyronaridine combination in adult participants with acute uncomplicated malaria due to P. falciparum. Primary Endpoint - Incidence, severity, and seriousness of study intervention-related TEAEs, as per CTCAE v 5.0 Additional endpoints related to safety and tolerability up to Day 29 (± 2 days): laboratory assessments, ECGs, and vital signs. ;Part B Primary Objective - To describe clinical efficacy of the M5717-pyronaridine combination and of Pyramax in adult and adolescent participants with acute uncomplicated malaria due to P. falciparum •Endpoint - PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A Secondary Objective - To characterize the PK of M5717 and pyronaridine in adult participants with acute uncomplicated malaria due to P. falciparum. Secondary Endpoint: • PK profiles for M5717 and pyronaridine • PK parameters of M5717 and pyronaridine such as AUC 0-tlast, AUC 0-8, AUC 0-24, Cmax, t½, tmax, CL/F, VZ/F, when data permits;Part A Secondary Objective - To describe the clinical efficacy of the M5717-pyronaridine combination in adult participants with acute uncomplicated malaria due to P. falciparum Secondary Endpoint – Early treatment failure (ETF) defined as meeting any of the following: • Danger signs or severe malaria 1, 2, or 3 days after treatment, in the presence of parasitemia • Parasitemia 2 days after treatment higher than on day of treatment, irrespective of axillary temperature • Parasitemia 3 days after treatment with axillary temperature = 37.5°C • Parasitemia 3 days after treatment = 25% of count on day of treatment;Part A Secondary Objective - To describe the clinical efficacy of the M5717-pyronaridine combination in adult participants with acute uncomplicated malaria due to P. falciparum Secondary Endpoint: Late Clinical Failure (LCF) defined as: • Danger signs or severe malaria in the presence of parasitemia on any day between 4 and 28 days after treatment (i.e., between Days 5 and 29) in participants who did not previously meet any of the criteria of ETF • Presence of parasitemia on any day between 4 and 28 days after treatment with axillary temperature = 37.5°C in participants who did not previously meet any of the criteria of ETF;Part A Secondary Objective - To describe the clinical efficacy of the M5717-pyronaridine combination in adult participants with acute uncomplicated malaria due to P. falciparum Secondary Endpoint: Late parasitological failure (LPF) defined as: • Presence of parasitemia on any day between 7 and 28 days after treatment (i.e., between Days 8 and 29) with axillary temperature < 37.5°C in p | — |
Countries
Burkina Faso, Gabon, Mozambique, Uganda
Contacts
Public ContactHenk Badenhorst
Senior Clinical Research Manager at ICON performing services on behalf of Merck Healthcare KGaA
Outcome results
None listed