Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)

NCT05689047 | Completed Phase 2 Results DMC

• 1 other identifier: MS201618_0033
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this study was to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria.

Conditions

Acute Malaria

Keywords

M5717; Plasmodium mutants; Acute Malaria; Pyronaridine; Plasmodium falciparum; Polymerase chain reaction; Adequate Clinical and Parasitological Response; Plasmodium eukaryotic translation Elongation Factor 2

Outcome Measures

Primary Outcomes (5)

• Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs

  An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.

  Day 1 up to Day 43

• Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters

  Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.

  Day 1 up to Day 29

• Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings

  Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

  Day 1 up to Day 29

• Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

  Day 1 up to Day 29

• Cohort B0: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)

  PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) was 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 Early treatment failure (ETF), Late clinical failure (LCF), or Late parasitological failure (LPF).

  At Day 29

Secondary Outcomes (21)

• Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine

  Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

• Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717 and Pyronaridine

  Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

• Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of M5717 and Pyronaridine

  Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

• Cohort A and Cohort B0: Apparent Total Clearance (CL/F) of M5717 and Pyronaridine

  Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

• Cohort A and Cohort B0: Maximum Plasma Concentration (Cmax) of M5717 and Pyronaridine

  Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Study Arms (2)

Part A: Safety Run-in Cohort M5717+Pyronaridine

EXPERIMENTAL

M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively.

Drug: M5717 330 mg; Drug: Pyronaridine 360 mg

Part B: Dose escalation cohort; M5717+Pyronaridine

EXPERIMENTAL

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.

Drug: M5717 500 mg; Drug: M5717 660 mg; Drug: Pyronaridine 360 mg; Drug: Pyronaridine 540 mg; Drug: Pyronaridine 720 mg

Interventions

M5717 330 mg DRUG

Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.

Part A: Safety Run-in Cohort M5717+Pyronaridine

M5717 500 mg DRUG

Adolescent participants with weight less than (\<) 45 kilograms (kg) will receive orally 500 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.

Part B: Dose escalation cohort; M5717+Pyronaridine

M5717 660 mg DRUG

Adult and adolescent participants with weight more than or equal to (\>=) 45 kg will receive orally 660 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.

Part B: Dose escalation cohort; M5717+Pyronaridine

Pyronaridine 360 mg DRUG

Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.

Part A: Safety Run-in Cohort M5717+Pyronaridine

Pyronaridine 540 mg DRUG

Participants with weight \>=45 to \<65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition.

Part B: Dose escalation cohort; M5717+Pyronaridine

Pyronaridine 720 mg DRUG

Participants with weight \>=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition.

Part B: Dose escalation cohort; M5717+Pyronaridine

Eligibility Criteria

• Age: 12 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (5)

Institut de Recherche en Sciences de la Santé (IRSS)

Nanoro, Burkina Faso

Location

Groupe de Recherche Action en Santé (GRAS)

Ouagadougou, Burkina Faso

Location

Centre de Recherches Médicales de Lambaréné (CERMEL)

Lambaréné, Gabon

Location

Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)

Maputo, Mozambique

Location

Infectious Diseases Research Collaboration (IDRC)

Tororo, Uganda

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Acute malaria; Malaria, Falciparum

Interventions

pyronaridine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: January 18, 2023
• Study Start: March 29, 2023
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: August 27, 2025
• Results First Posted: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

GA (1); UG (1); BU (2); MO (1)