Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
Phase 2
Completed
- Conditions
- Acute Malaria
- Interventions
- Drug: M5717 330 mgDrug: M5717 500 mgDrug: Pyronaridine-artesunate (Pyramax) 360 mg/120 mgDrug: M5717 660 mgDrug: Pyronaridine-artesunate (Pyramax) 720 mg/240 mg
- Registration Number
- NCT05689047
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria. Pyramax (Artesunate/Pyronaridine) will act as an internal control providing reference safety data and a benchmark for the efficacy evaluation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Inclusion Criteria
- Participants with microscopic confirmation of acute uncomplicated Plasmodium falciparum using Giemsa-stained thick and thin film
- P. falciparum parasitemia of 1,000 to 50,000 asexual parasites/microliter of blood in Part A and P. falciparum parasitemia of >1,000 to <= 150,000 asexual parasites/microliter of blood in Part B
- Axillary temperature >= 37.5 degree Celsius or tympanic temperature >= 38.0 degree Celsius (use as per Coronavirus disease 2019 (COVID-19) protocols at the site [only at Screening]), or history of fever during the previous 24 hours (at least documented verbally)
- The Investigator confirms that each participant agrees to use appropriate contraception and barriers, if applicable
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Mixed Plasmodium infections as per thin film microscopy results
- Signs and symptoms of severe malaria according to World Health Organisation (WHO) 2021 criteria (WHO 2021)
- 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
- Known history or evidence of clinically significant disorders such as, cardiovascular, respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological [including known Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS)], neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions, or other abnormality (including head trauma)
- Previous treatment with pyronaridine as part of a combination therapy during the last 3 months
- 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)
- Participants taking medications prohibited by the protocol
- Other protocol defined exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Safety Run-in Cohort M5717+Pyronaridine M5717 330 mg M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively. Part B: Dose escalation cohort; M5717+Pyronaridine M5717 500 mg After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen. Part B: Dose escalation cohort; M5717+Pyronaridine M5717 660 mg After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen. Pyronaridine-artesunate Pyronaridine-artesunate (Pyramax) 360 mg/120 mg Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen. Pyronaridine-artesunate Pyronaridine- artesunate (Pyramax) 540 mg/180 mg Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen. Pyronaridine-artesunate Pyronaridine-artesunate (Pyramax) 720 mg/240 mg Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen. Part A: Safety Run-in Cohort M5717+Pyronaridine Pyronaridine 360 mg M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively. Part B: Dose escalation cohort; M5717+Pyronaridine Pyronaridine 360 mg After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen. Part B: Dose escalation cohort; M5717+Pyronaridine Pyronaridine 720 mg After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen. Part B: Dose escalation cohort; M5717+Pyronaridine Pyronaridine 540 mg After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen.
- Primary Outcome Measures
Name Time Method Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Day 1 up to Day 43 Part A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters, Vital Signs and 12-lead Electrocardiogram (ECG) Findings Day 1 up to Day 29 Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) At Day 29
- Secondary Outcome Measures
Name Time Method Part A and Part B: Percentage of Participants with Crude (PCR-uncorrected) Efficacy At Day 9 Part A and Part B: Pharmacokinetic Plasma Concentration of M5717 and Pyronaridine Day 1 up to Day 43 Part A and Part B: Percentage of Participants with Early Treatment Failure (ETF) Day 1,2 and 3 Part A and Part B: Percentage of Participants with Late Clinical Failure (LCF) From Day 5 to Day 29 Part A and Part B: Percentage of Participants with Late parasitological failure (LPF) From Day 8 to Day 29 Part A and Part B: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR) Day 15, 29 and 43 Part A: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) Day 15, 29 and 43 Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) At Day 15 and 43 Part A and Part B: Parasite Clearance Time as Estimated by Kaplan-Meier Method Day 1 up to Day 43 Part A and Part B: Time to Re-Emergence as Estimated by Kaplan-Meier Method Up to Day 43 Part A and Part B: Parasite Reduction Rate Upto 48 hours post-dose Part A and Part B: Percentage of Participants with PCR-Adjusted Efficacy At Day 9 Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Up to Day 43 Part A and Part B: Time to Fever Clearance as Estimated by Kaplan-Meier Method Day 1 up to Day 29 Part A and Part B: Time to Recrudescence as Estimated by Kaplan-Meier Method Day 1 up to Day 43 Part A and Part B: Time to Re-Infection as Estimated by Kaplan-Meier Method Up to Day 43
Trial Locations
- Locations (5)
Infectious Diseases Research Collaboration (IDRC)
🇺🇬Tororo, Uganda
Groupe de Recherche Action en Santé (GRAS)
🇧🇫Ouagadougou, Burkina Faso
Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
🇲🇿Maputo, Mozambique
Institut de Recherche en Sciences de la Santé (IRSS)
🇧🇫Nanoro, Burkina Faso
Centre de Recherches Médicales de Lambaréné (CERMEL)
🇬🇦Lambarene, Gabon