Clinical trial NCT05689047: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 38
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
timeFrame: Day 1 up to Day 43
measure: Part A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters, Vital Signs and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 29
measure: Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
timeFrame: At Day 29
Secondary outcomes:
measure: Part A and Part B: Pharmacokinetic Plasma Concentration of M5717 and Pyronaridine
timeFrame: Day 1 up to Day 43
measure: Part A and Part B: Percentage of Participants with Early Treatment Failure (ETF)
timeFrame: Day 1,2 and 3
measure: Part A and Part B: Percentage of Participants with Late Clinical Failure (LCF)
timeFrame: From Day 5 to Day 29
measure: Part A and Part B: Percentage of Participants with Late parasitological failure (LPF)
timeFrame: From Day 8 to Day 29
measure: Part A and Part B: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
timeFrame: Day 15, 29 and 43
measure: Part A: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
timeFrame: Day 15, 29 and 43
measure: Part B: Percentage of Participants with Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
timeFrame: At Day 15 and 43
measure: Part A and Part B: Percentage of Participants with Crude (PCR-uncorrected) Efficacy
timeFrame: At Day 9
measure: Part A and Part B: Percentage of Participants with PCR-Adjusted Efficacy
timeFrame: At Day 9
measure: Part A and Part B: Parasite Reduction Rate
timeFrame: Upto 48 hours post-dose
measure: Part A and Part B: Time to Fever Clearance as Estimated by Kaplan-Meier Method
timeFrame: Day 1 up to Day 29
measure: Part A and Part B: Parasite Clearance Time as Estimated by Kaplan-Meier Method
timeFrame: Day 1 up to Day 43
measure: Part A and Part B: Time to Recrudescence as Estimated by Kaplan-Meier Method
timeFrame: Day 1 up to Day 43
measure: Part A and Part B: Time to Re-Infection as Estimated by Kaplan-Meier Method
timeFrame: Up to Day 43
measure: Part A and Part B: Time to Re-Emergence as Estimated by Kaplan-Meier Method
timeFrame: Up to Day 43
measure: Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
timeFrame: Up to Day 43
Other outcomes:
Locations:
city: Nanoro
country: Burkina Faso
facility: Institut de Recherche en Sciences de la Santé (IRSS)
city: Ouagadougou
country: Burkina Faso
facility: Groupe de Recherche Action en Santé (GRAS)
city: Lambarene
country: Gabon
facility: Centre de Recherches Médicales de Lambaréné (CERMEL)
city: Maputo
country: Mozambique
facility: Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
city: Tororo
country: Uganda
facility: Infectious Diseases Research Collaboration (IDRC)
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: