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

February 29, 2024 updated by: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

137

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Burkina Faso
      • Nanoro, Burkina Faso
        • Not yet recruiting
        • Institut de Recherche en Sciences de la Santé (IRSS)
        • Contact:
        • Principal Investigator:
          • Moussa Lingani
      • Ouagadougou, Burkina Faso
        • Not yet recruiting
        • Groupe de Recherche Action en Sante (GRAS)
        • Contact:
        • Principal Investigator:
          • B.Alfred Tiono
  • Gabon
      • Lambarene, Gabon
        • Not yet recruiting
        • Centre de Recherches Médicales de Lambaréné (CERMEL)
        • Contact:
        • Principal Investigator:
          • Zoleko Manego Rella
  • Mozambique
      • Maputo, Mozambique
        • Not yet recruiting
        • Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
        • Contact:
        • Principal Investigator:
          • Quique Bassat
  • Uganda
      • Tororo, Uganda
        • Recruiting
        • Infectious Diseases Research Collaboration (IDRC)
        • Contact:
        • Principal Investigator:
          • Yeka Adoke

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Safety Run-in Cohort M5717+Pyronaridine
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
Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.
Drug: Pyronaridine 360 mg
Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.
Drug: Pyronaridine 360 mg
Participants with weight >=24 to <45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition.
Experimental: Part B: Dose escalation cohort; M5717+Pyronaridine
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: Pyronaridine 360 mg
Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.
Drug: Pyronaridine 360 mg
Participants with weight >=24 to <45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition.
Drug: M5717 500 mg
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.
Drug: M5717 660 mg
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.
Drug: Pyronaridine 540 mg
Participants with weight >=45 to <65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Drug: Pyronaridine 720 mg
Participants with weight >=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Active Comparator: Pyronaridine-artesunate
Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen.
Drug: Pyronaridine-artesunate (Pyramax) 360 mg/120 mg
Participants with weight >=24 to <45 kg will receive dose of 360/120 mg dose of Pyronaridine- artesunate (Pyramax) tablets under fasting condition.
Drug: Pyronaridine- artesunate (Pyramax) 540 mg/180 mg
Participants with weight >=45 to <65 kg will receive 540/180 mg dose of Pyronaridine-artesunate (Pyramax) tablets under fasting condition.
Drug: Pyronaridine-artesunate (Pyramax) 720 mg/240 mg
Participants with weight >=65 kg will receive 720/240 mg dose of Pyronaridine- artesunate (Pyramax) tablets under fasting condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time Frame: Day 1 up to Day 43
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
Time Frame: Day 1 up to Day 29
Day 1 up to Day 29
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame: At Day 29
At Day 29

Secondary Outcome Measures

Outcome Measure
Time Frame
Part A and Part B: Pharmacokinetic Plasma Concentration of M5717 and Pyronaridine
Time Frame: Day 1 up to Day 43
Day 1 up to Day 43
Part A and Part B: Percentage of Participants with Early Treatment Failure (ETF)
Time Frame: Day 1,2 and 3
Day 1,2 and 3
Part A and Part B: Percentage of Participants with Late Clinical Failure (LCF)
Time Frame: From Day 5 to Day 29
From Day 5 to Day 29
Part A and Part B: Percentage of Participants with Late parasitological failure (LPF)
Time Frame: From Day 8 to Day 29
From Day 8 to Day 29
Part A and Part B: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Time Frame: Day 15, 29 and 43
Day 15, 29 and 43
Part A: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame: Day 15, 29 and 43
Day 15, 29 and 43
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame: At Day 15 and 43
At Day 15 and 43
Part A and Part B: Percentage of Participants with Crude (PCR-uncorrected) Efficacy
Time Frame: At Day 9
At Day 9
Part A and Part B: Percentage of Participants with PCR-Adjusted Efficacy
Time Frame: At Day 9
At Day 9
Part A and Part B: Parasite Reduction Rate
Time Frame: Upto 48 hours post-dose
Upto 48 hours post-dose
Part A and Part B: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Time Frame: Day 1 up to Day 29
Day 1 up to Day 29
Part A and Part B: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Time Frame: Day 1 up to Day 43
Day 1 up to Day 43
Part A and Part B: Time to Recrudescence as Estimated by Kaplan-Meier Method
Time Frame: Day 1 up to Day 43
Day 1 up to Day 43
Part A and Part B: Time to Re-Infection as Estimated by Kaplan-Meier Method
Time Frame: Up to Day 43
Up to Day 43
Part A and Part B: Time to Re-Emergence as Estimated by Kaplan-Meier Method
Time Frame: Up to Day 43
Up to Day 43
Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time Frame: Up to Day 43
Up to Day 43

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2023

Primary Completion (Estimated)

September 18, 2024

Study Completion (Estimated)

September 18, 2024

Study Registration Dates

First Submitted

January 9, 2023

First Submitted That Met QC Criteria

January 9, 2023

First Posted (Actual)

January 18, 2023

Study Record Updates

Last Update Posted (Actual)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS201618_0033

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing 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

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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