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

Primary Purpose

Acute Malaria

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
M5717 330 mg
M5717 500 mg
M5717 660 mg
Pyronaridine 360 mg
Pyronaridine 360 mg
Pyronaridine 540 mg
Pyronaridine 720 mg
Pyronaridine-artesunate (Pyramax) 360 mg/120 mg
Pyronaridine- artesunate (Pyramax) 540 mg/180 mg
Pyronaridine-artesunate (Pyramax) 720 mg/240 mg
Sponsored by
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Malaria focused on measuring M5717, Plasmodium mutants, Acute Malaria, Pyronaridine, Plasmodium falciparum, Polymerase chain reaction, Adequate Clinical and Parasitological Response, Plasmodium eukaryotic translation Elongation Factor 2

Eligibility Criteria

12 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut de Recherche en Sciences de la Santé (IRSS)
  • Groupe de Recherche Action en Santé (GRAS)
  • Centre de Recherches Médicales de Lambaréné (CERMEL)
  • Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
  • Infectious Diseases Research Collaboration (IDRC)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Part A: Safety Run-in Cohort M5717+Pyronaridine

Part B: Dose escalation cohort; M5717+Pyronaridine

Pyronaridine-artesunate

Arm Description

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

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 (Pyramax) once daily in a 3-day treatment regimen.

Outcomes

Primary Outcome Measures

Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Part A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters, Vital Signs and 12-lead Electrocardiogram (ECG) Findings
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)

Secondary Outcome Measures

Part A and Part B: Pharmacokinetic Plasma Concentration of M5717 and Pyronaridine
Part A and Part B: Percentage of Participants with Early Treatment Failure (ETF)
Part A and Part B: Percentage of Participants with Late Clinical Failure (LCF)
Part A and Part B: Percentage of Participants with Late parasitological failure (LPF)
Part A and Part B: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Part A: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Part A and Part B: Percentage of Participants with Crude (PCR-uncorrected) Efficacy
Part A and Part B: Percentage of Participants with PCR-Adjusted Efficacy
Part A and Part B: Parasite Reduction Rate
Part A and Part B: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Part A and Part B: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Part A and Part B: Time to Recrudescence as Estimated by Kaplan-Meier Method
Part A and Part B: Time to Re-Infection as Estimated by Kaplan-Meier Method
Part A and Part B: Time to Re-Emergence as Estimated by Kaplan-Meier Method
Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs

Full Information

First Posted
January 9, 2023
Last Updated
October 9, 2023
Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT05689047
Brief Title
Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2023 (Actual)
Primary Completion Date
November 24, 2023 (Anticipated)
Study Completion Date
November 24, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
137 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: Safety Run-in Cohort M5717+Pyronaridine
Arm Type
Experimental
Arm Description
M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively.
Arm Title
Part B: Dose escalation cohort; M5717+Pyronaridine
Arm Type
Experimental
Arm Description
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.
Arm Title
Pyronaridine-artesunate
Arm Type
Active Comparator
Arm Description
Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen.
Intervention Type
Drug
Intervention Name(s)
M5717 330 mg
Intervention Description
Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.
Intervention Type
Drug
Intervention Name(s)
M5717 500 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
M5717 660 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine 360 mg
Intervention Description
Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine 360 mg
Intervention Description
Participants with weight >=24 to <45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine 540 mg
Intervention Description
Participants with weight >=45 to <65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine 720 mg
Intervention Description
Participants with weight >=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine-artesunate (Pyramax) 360 mg/120 mg
Intervention Description
Participants with weight >=24 to <45 kg will receive dose of 360/120 mg dose of Pyronaridine- artesunate (Pyramax) tablets under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine- artesunate (Pyramax) 540 mg/180 mg
Intervention Description
Participants with weight >=45 to <65 kg will receive 540/180 mg dose of Pyronaridine-artesunate (Pyramax) tablets under fasting condition.
Intervention Type
Drug
Intervention Name(s)
Pyronaridine-artesunate (Pyramax) 720 mg/240 mg
Intervention Description
Participants with weight >=65 kg will receive 720/240 mg dose of Pyronaridine- artesunate (Pyramax) tablets under fasting condition.
Primary Outcome Measure Information:
Title
Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time Frame
Day 1 up to Day 43
Title
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
Title
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame
At Day 29
Secondary Outcome Measure Information:
Title
Part A and Part B: Pharmacokinetic Plasma Concentration of M5717 and Pyronaridine
Time Frame
Day 1 up to Day 43
Title
Part A and Part B: Percentage of Participants with Early Treatment Failure (ETF)
Time Frame
Day 1,2 and 3
Title
Part A and Part B: Percentage of Participants with Late Clinical Failure (LCF)
Time Frame
From Day 5 to Day 29
Title
Part A and Part B: Percentage of Participants with Late parasitological failure (LPF)
Time Frame
From Day 8 to Day 29
Title
Part A and Part B: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Time Frame
Day 15, 29 and 43
Title
Part A: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame
Day 15, 29 and 43
Title
Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
Time Frame
At Day 15 and 43
Title
Part A and Part B: Percentage of Participants with Crude (PCR-uncorrected) Efficacy
Time Frame
At Day 9
Title
Part A and Part B: Percentage of Participants with PCR-Adjusted Efficacy
Time Frame
At Day 9
Title
Part A and Part B: Parasite Reduction Rate
Time Frame
Upto 48 hours post-dose
Title
Part A and Part B: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Time Frame
Day 1 up to Day 29
Title
Part A and Part B: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Time Frame
Day 1 up to Day 43
Title
Part A and Part B: Time to Recrudescence as Estimated by Kaplan-Meier Method
Time Frame
Day 1 up to Day 43
Title
Part A and Part B: Time to Re-Infection as Estimated by Kaplan-Meier Method
Time Frame
Up to Day 43
Title
Part A and Part B: Time to Re-Emergence as Estimated by Kaplan-Meier Method
Time Frame
Up to Day 43
Title
Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
Time Frame
Up to Day 43

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Communication Center
Phone
+49 6151 72 5200
Email
service@emdgroup.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Institut de Recherche en Sciences de la Santé (IRSS)
City
Nanoro
Country
Burkina Faso
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
+226 70675780
Email
lingani10@gmail.com
First Name & Middle Initial & Last Name & Degree
Moussa Lingani
Facility Name
Groupe de Recherche Action en Santé (GRAS)
City
Ouagadougou
Country
Burkina Faso
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
+226 7028 5726
Email
a.tiono@gras.bf
First Name & Middle Initial & Last Name & Degree
B.Alfred Tiono
Facility Name
Centre de Recherches Médicales de Lambaréné (CERMEL)
City
Lambarene
Country
Gabon
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
+241 7715 15748
Email
manegorella@yahoo.fr
First Name & Middle Initial & Last Name & Degree
Zoleko Manego Rella
Facility Name
Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
City
Maputo
Country
Mozambique
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
0034 932275400
Ext
4121
Email
Quique.bassat@isglobal.org
First Name & Middle Initial & Last Name & Degree
Quique Bassat
Facility Name
Infectious Diseases Research Collaboration (IDRC)
City
Tororo
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
Phone
+256 7724 73533
Email
yadoke@yahoo.com
First Name & Middle Initial & Last Name & Degree
Yeka Adoke

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://bit.ly/IPD21
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201618_0033
Description
Trial Awareness and Transparency website

Learn more about this trial

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

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