Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202312609154425 Date of Approval: 14/12/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title MS201618_0034 - Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents with Plasmodium falciparum Malaria Infection (CAPTURE-2).
Official scientific title Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents with Plasmodium falciparum Malaria Infection (CAPTURE-2).
Brief summary describing the background and objectives of the trial This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data. Artemisinin-based combination therapies (ACTs) have been the gold standard for acule uncomplicaled P. falciparum malaria, but the increasing reports of emergent resistant strains to artemisinin-related compound therapies makes it necessary ta look for new therapeutic tools. ln this context, the current study intends to explore in a Proof of Concept the safety, preliminary efficacy, and pharmacokinetics (PK) of M5717 (free base) in combination with pyronaridine (tetraphosphate). An ACT containing combination pyronaridine-artesunate (Pyramax) will be used as internal control, mainly for safety purposes.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CAPTURE 2
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 10/09/2023
Actual trial start date 28/11/2023
Anticipated date of last follow up 30/04/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 192
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group M5717 and Pyronaridine tetraphosphate M5717: 60 mg, 200 mg, 660 mg Pyronaridine tetraphosphate: 720 mg, 540 mg 1 day treatment regimen Cohort 1: Single dose 60 mg M5717 plus 720 mg (participants ≥ 65 kg) or 540 mg (participants ≥ 45 to < 65 kg) pyronaridine Cohort 2: Single dose 200 mg M5717 plus 720 mg (participants ≥ 65 kg) or 540 mg (participants ≥ 45 to < 65 kg) pyronaridine Cohort 3: Single dose 660 mg M5717 plus 720 mg (participants ≥ 65 kg) or 540 mg (adolescents) pyronaridine (participants ≥ 45 to < 65 kg) On Day 1 participants will receive a single dose of M5717 of either 60, 200, or 660 mg in loose combination with a single dose of pyronaridine. On Day 1 participants will receive a single dose of 720 mg (participants ≥ 65 kg) or 540 mg (participants ≥ 45 to < 65 kg) pyronaridine irrespective of the dose of M5717. 45 participants per treatment cohort will lead to total of 180 evaluable participants (including control group) considering dropout rate. 135
Control Group Atovaquone proguanil hydrochloride 1,000/400 mg 3-day treatment regimen (4 tablets per day) Cohort 4: 3 doses of 1,000 mg/400 mg atovaquone – proguanil (Malarone) on 3 consecutive days Participants in Cohort 4 will receive 3 doses of atovaquone – proguanil on Days 1, 2, and 3 45 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Participants with Asymptomatic Plasmodium falciparum Malaria with no Fever or other sign of Acute Uncomplicated Malaria and, with Microscopic confirmation using Giemsa-stained thick film, and a Parasitemia of >= 40 to <= 10,000 Asexual Parasites/Microliter (μL) of Blood. • Axillary Temperature < 37.0 degree Celcius (ºC) or oral/Tympanic/rectal Temperature< 37.5ºC; without history of fever during the previous 48 hours. • Have a body weight >= 45 kilogram (kg) • Participants capable of giving Signed Informed consent which includes Compliance with the requirements and restriction listed in the Informed consent form • Other Protocol defined Inclusion Criteria could apply • Participants with any disease requiring Chronic Treatment • Participants with any Preplanned surgery during the study • Participants with any previous Treatment with pyronaridine as part of a combination therapy during the last 3 months • Participants with any adequate Hematological, Hepatic, and renal function as defined in the Protocol • Other protocol defined Exclusion Criteria could apply Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 55 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 26/07/2023 London School of Hygiene and Tropical Medicine
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/07/2023 The Gambia Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
C/O MRC Unit The Gambia at LSHTM, Fajara Banjul 0000 Gambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 12/04/2023 Comite d Ethique pour researche en sante
Ethics Committee Address
Street address City Postal code Country
Building Lamizana, 09BP24 Ooagadougou 09 0000 Burkina Faso
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/04/2023 TDRC Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
PO Box 71769 Ndola 0000 Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/06/2023 The Nairobi Hospital Ethics and Research Committee
Ethics Committee Address
Street address City Postal code Country
PO Box 30026 Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to Parasitemia Since Negative Blood Smear after Treatment From Study Start Day 1 up to End of Study - approximately 12 weeks
Secondary Outcome Percentage of Participants with Parasitemia (positive blood smear). From Study Start Day 1 up to End of Study - approximately 12 weeks
Secondary Outcome Percentage of Participants with Polymerase Chain Reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to new Infections as determined by Genotyping using PCR Techniques) From Study Start Day 1 up to End of Study - approximately 12 weeks
Secondary Outcome Percentage of Participants with PCR-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques) From Study Start Day 1 up to End of Study - approximately 12 weeks
Secondary Outcome Parasite Clearance Time Time from dosing to the first negative -no parasites- blood film -microscopy- , assessed up to 12 weeks
Secondary Outcome Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs From Study Start Day 1 up to End of Study - approximately 12 Weeks
Secondary Outcome Pharmacokinetic (PK) Plasma Concentrations of M5717 and Pyronaridine Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and -24 hours- on Day 2
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRC Unit the Gambia at LSHTM Atlantic Boulevard, Fajara Kanifing Municipality Gambia
Tropical Diseases Research Centre 6th and 7th Floors, Main Building, Ndola Teaching Hospital Ndola Zambia
Groupe de Researche Action en Sante GRAS 03 BP 10248 Ouagadougou 06 Burkina Faso
Victoria Biomedical Research Institute VIBRI Kisumu Country Referral Hospital, Off Ang-awa Road, PO Box 7180-40100 Kusumu 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Merck Healthcare KGaA Frankfurter Strasse 250 Darmstadt 64293 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Merck Healthcare KGaA Frankfurter Strasse 250 Darmstadt 64293 Germany Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Umberto DAlessandro udalessandro@mrc.gm +2204495835 Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Kanifing Municipality Gambia Coordinating Investigator
Role Name Email Phone Street address
Public Enquiries Henk Badenhorst henk.badenhorst@external.merckgroup.com +27112311900 ICON Global Strategic Solutions, Building 29 2nd Floor Woodlands Office Park, Woodlands Drive, Woodmead
City Postal code Country Position/Affiliation
Johannesburg 0001 South Africa Senior Clinical Research Manager at ICON performing services on behalf of Merck Healthcare KGaA
Role Name Email Phone Street address
Scientific Enquiries Birgitta Leopoldt birgitta.leopold@merckgroup.com +4915114540511 Frankfurter Str. 250
City Postal code Country Position/Affiliation
Darmstadt 64293 Germany RA Strategic Project Leader
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Sponsor is 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 Analytic Code,Clinical Study Report,Statistical Analysis Plan,Study Protocol 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 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.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://bit.ly/IPD21 No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information