Acute MalariaPhase 2NCT05689047
Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
A Phase 2 study testing M5717 330 mg, M5717 500 mg and M5717 660 mg in people with Acute Malaria, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 5 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 55 years
- Conditions the study is for
- Acute Malaria
- What is being tested?
- M5717 330 mg, M5717 500 mg and M5717 660 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 29 Mar 2023to 28 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Burkina Faso2 sites
Institut de Recherche en Sciences de la Santé (IRSS)
Nanoro
Groupe de Recherche Action en Santé (GRAS)
Ouagadougou
Mozambique1 site
Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
Maputo
About this study
Official title: Phase IIa Proof of Concept, Multicenter, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 Plus Pyronaridine Administered Once Daily for 1 or 2 Days to Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
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
- Being tested
- M5717 330 mg, M5717 500 mg, M5717 660 mg, Pyronaridine 360 mg, Pyronaridine 540 mg
- Keywords
- M5717, Plasmodium mutants, Acute Malaria, Pyronaridine, Plasmodium falciparum, Polymerase chain reaction, Adequate Clinical and Parasitological Response, Plasmodium eukaryotic translation Elongation Factor 2
- Medical subject headings
- Acute malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M5717 330 mgDrug
Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.
M5717 500 mgDrug
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.
M5717 660 mgDrug
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.
Pyronaridine 360 mgDrug
Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.
Pyronaridine 360 mgDrug
Participants with weight >=24 to <45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition.
Pyronaridine 540 mgDrug
Participants with weight >=45 to <65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Pyronaridine 720 mgDrug
Participants with weight >=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: M5717 500 mg; Drug: M5717 660 mg; Drug: Pyronaridine 360 mg; Drug: Pyronaridine 540 mg; Drug: Pyronaridine 720 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. Calculated as AUC0-inf = AUC0-tlast + Clast pred/ lambda z.
Measured: 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
The AUC from time zero (dosing time) to 24 hours post dose was calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Measured: 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
The AUC from time zero (= dosing time) to the time of the last quantifiable concentration (tlast), calculated using the mixed log linear trapezoidal rule (linear up, log down)
Measured: 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
The apparent total body clearance of study intervention following extravascular administration. CL/ F was calculated by oral dose divided by Area under the plasma concentration curve 0- infinity.
Measured: 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
Cmax was taken directly from the observed concentration-time curve.
Measured: 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 Terminal Half-Life of M5717 and Pyronaridine
t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.
Measured: 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: Time to Reach Maximum Plasma Concentration (Tmax) of M5717 and Pyronaridine
tmax was obtained directly from the concentration versus time curve.
Measured: 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 Volume of Distribution (Vz/F) of M5717 and Pyronaridine
The apparent volume of distribution during the terminal phase following extravascular administration. Vz/F = Dose/(AUC0-∞*λz) following single dose.
Measured: 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: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Post Dose (AUC0-24h/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero to 24 hours post dose. Normalized using the dose, using the formula AUC0-24/Dose.
Measured: 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: Dose Normalized Area Under the Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Normalized using the dose, using the formula AUC0-tlast /Dose.
Measured: 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: Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero extrapolated to infinity. Normalized using dose, using the formula AUC0-∞ /Dose.
Measured: 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: Terminal Elimination Rate Constant (Lambda z) of M5717 and Pyronaridine
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Measured: 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: Dose Normalized Maximum Concentration (Cmax/Dose) of M5717 and Pyronaridine
The dose normalized maximum concentration. Normalized using the dose, and the formula Cmax /Dose.
Measured: 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: Percentage of Participants With Early Treatment Failure (ETF)
Early treatment failure (ETF) was defined as meeting any of the following : 1. Danger signs or severe malaria 1, 2, or 3 days after treatment, in the presence of parasitemia2. Parasitemia 2 days after treatment higher than on day of treatment, irrespective of axillary temperature
- Parasitemia 3 days after treatment with temperature ≥ 37.5°C 3. Parasitemia 3 days after treatment ≥ 25% of count on day of treatment. ETF rate will be estimated with 95% confidence intervals. Confidence intervals was derived by use of Wilson's score method.
Measured: Up to Day 3 post treatment on Day 1
Cohort A and Cohort B0: Percentage of Participants With Late Clinical Failure (LCF)
Late clinical failure (LCF) was defined as:1. 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. 2. Presence of parasitemia on any day between 4 and 28 days after treatment with temperature ≥ 37.5°C in participants who did not previously meet any of the criteria of ETF. LCF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
Measured: Day 1 up to Day 29
Cohort A and Cohort B0: Percentage of Participants With Late Parasitological Failure (LPF)
Late parasitological failure (LPF) was defined as: Presence of parasitemia on any day between 7 and 28 days after treatment (i.e., between Days 8 and 29) with temperature < 37.5°C in participants who did not previously meet any of the criteria of ETF or LCF. LPF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
Measured: From Day 8 to Day 29
Cohort A: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
PCR-adjusted ACPR 28 and 42 days after treatment 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.
Measured: Day 28 and 42
Cohort A and B0: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Crude ACPR 28 and 42 days after first dose is defined as absence of parasitemia (parasite count = 0) from thick smear/microscopy, irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.
Measured: Day 28 and 42
Cohort A and Cohort B0: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Fever clearance time was defined as the time from first dosing to the first measurement of temperature < 37.5°C for 2 consecutive temperature readings plus confirmed normal temperature 24 h after the first normal body temperature reading. This analysis was done on participants with fever.
Measured: Day 1 up to Day 29
Cohort A and Cohort B0: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Parasite clearance time defined as time from dosing to the first negative (no parasites) film
Measured: Day 1 up to Day 43
Cohort B0: 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.
Measured: Day 1 up to Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2023
- Study start29 Mar 2023
- Primary completion28 May 2024
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05689047
- Sponsor's protocol ID
- MS201618_0033
- Status last verified
- Aug 2025
- First submitted
- 9 Jan 2023
- Last updated
- 27 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Publications
Mombo-Ngoma G, Adoke Y, Manego RZ, Tiono AB, Tinto H, Bassat Q, Spangenberg T, Bougouma EC, Kremsner PG, Lingani M, Kibuuka A, Aide P, Kim W, Marrast AC, Tappert A, Oeuvray C, Bodding M, Seitzinger A, Okebe J. Safety, pharmacokinetics, and antimalarial efficacy of single-dose cabamiquine-pyronaridine combination therapy for the treatment of adults and adolescents with acute uncomplicated Plasmodium falciparum malaria (CAPTURE 1): a prospective, multicentre, open-label, phase 2a study. Lancet Infect Dis. 2026 Jul 16:S1473-3099(26)00233-1. doi: 10.1016/S1473-3099(26)00233-1. Online ahead of print.
PubMed 42462745
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Proof of Concept, Multicenter, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 Plus Pyronaridine Administered Once Daily for 1 or 2 Days to Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
- ClinicalTrials.gov ID
- NCT05689047
- Acronym / sponsor ID
- MS201618_0033
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2023 (actual)
- Primary completion
- 28 May 2024 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 18 Jan 2023 (actual)
- Results
- Posted 27 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Safety Run-in Cohort M5717+Pyronaridine | Experimental | Drug: M5717 330 mg, Drug: Pyronaridine 360 mgM5717 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 | Experimental | Drug: M5717 500 mg, Drug: M5717 660 mg, Drug: Pyronaridine 360 mg, Drug: Pyronaridine 540 mg, Drug: Pyronaridine 720 mgAfter 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. |
Who may qualify
- Ages
- 12 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M5717 330 mgParticipants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition. | Drug | Part A: Safety Run-in Cohort M5717+Pyronaridine |
| M5717 500 mgAdolescent 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. | Drug | Part B: Dose escalation cohort; M5717+Pyronaridine |
| M5717 660 mgAdult 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. | Drug | Part B: Dose escalation cohort; M5717+Pyronaridine |
| Pyronaridine 360 mgParticipants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition. | Drug | Part A: Safety Run-in Cohort M5717+Pyronaridine |
| Pyronaridine 360 mgParticipants with weight >=24 to <45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition. | Drug | Part B: Dose escalation cohort; M5717+Pyronaridine |
| Pyronaridine 540 mgParticipants with weight >=45 to <65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition. | Drug | Part B: Dose escalation cohort; M5717+Pyronaridine |
| Pyronaridine 720 mgParticipants with weight >=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. | Drug | Part B: Dose escalation cohort; M5717+Pyronaridine |
Primary outcome
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time frame: Day 1 up to Day 43
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.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters
Time frame: Day 1 up to Day 29
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.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Time frame: Day 1 up to Day 29
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.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Day 1 up to Day 29
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.
Cohort B0: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time frame: At Day 29
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).
21 secondary outcomes
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Terminal Half-Life of M5717 and Pyronaridine
Time frame: 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: Time to Reach Maximum Plasma Concentration (Tmax) of M5717 and Pyronaridine
Time frame: 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 Volume of Distribution (Vz/F) of M5717 and Pyronaridine
Time frame: 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: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Post Dose (AUC0-24h/Dose) of M5717 and Pyronaridine
Time frame: 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: Dose Normalized Area Under the Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of M5717 and Pyronaridine
Time frame: 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: Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞/Dose) of M5717 and Pyronaridine
Time frame: 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: Terminal Elimination Rate Constant (Lambda z) of M5717 and Pyronaridine
Time frame: 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: Dose Normalized Maximum Concentration (Cmax/Dose) of M5717 and Pyronaridine
Time frame: 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: Percentage of Participants With Early Treatment Failure (ETF)
Time frame: Up to Day 3 post treatment on Day 1
Cohort A and Cohort B0: Percentage of Participants With Late Clinical Failure (LCF)
Time frame: Day 1 up to Day 29
Cohort A and Cohort B0: Percentage of Participants With Late Parasitological Failure (LPF)
Time frame: From Day 8 to Day 29
Cohort A: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time frame: Day 28 and 42
Cohort A and B0: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Time frame: Day 28 and 42
Cohort A and Cohort B0: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Time frame: Day 1 up to Day 29
Cohort A and Cohort B0: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Time frame: Day 1 up to Day 43
Cohort B0: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time frame: Day 1 up to Day 43
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42462745Mombo-Ngoma G, Adoke Y, Manego RZ, Tiono AB, Tinto H, Bassat Q, Spangenberg T, Bougouma EC, Kremsner PG, Lingani M, Kibuuka A, Aide P, Kim W, Marrast AC, Tappert A, Oeuvray C, Bodding M, Seitzinger A, Okebe J. Safety, pharmacokinetics, and antimalarial efficacy of single-dose cabamiquine-pyronaridine combination therapy for the treatment of adults and adolescents with acute uncomplicated Plasmodium falciparum malaria (CAPTURE 1): a prospective, multicentre, open-label, phase 2a study. Lancet Infect Dis. 2026 Jul 16:S1473-3099(26)00233-1. doi: 10.1016/S1473-3099(26)00233-1. Online ahead of print.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing M5717 330 mg, M5717 500 mg and M5717 660 mg in people with Acute Malaria, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Burkina Faso, Gabon, Mozambique, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs (time frame: Day 1 up to Day 43). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05689047, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.