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.: PACTR202302602361661 Date of Approval: 01/02/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria (PLATINUM)
Official scientific title (PLATINUM): A multi-part, multi-center PLATform study to assess the efficacy, safety, tolerability and pharmacokinetics of anti-malarial agents administered as monotherapy and/or combination therapy IN patients with Uncomplicated Plasmodium falciparum Malaria
Brief summary describing the background and objectives of the trial Despite malaria being a preventable and curable disease, there were an estimated 241 million cases worldwide in 2020. In 2020, 95% of cases were in the World Health Organization African Region, and 99.7% of these were caused by Plasmodium falciparum. The infection leads to flu-like symptoms, including headache, slight fever, muscle pain, anorexia, nausea, and fatigue as parasitemia rises in the blood. If not promptly treated, patients may develop cerebral or severe malaria. These life-threatening complications can result in coma, acute respiratory distress, and severe anemia. In 2020, malaria was responsible for an estimated 627,000 deaths with children under the age of five accounting for 67% of malaria-related deaths. Research efforts have been focused on identifying drugs that display the appropriate pharmacologic properties to ensure potent, rapid, and sustained parasite killing with a simple and short treatment regimen in order to improve compliance and reduce the development of resistance. The target product profile for these new antimalarial agents is based on the requirements identified by the Medicines for Malaria Venture (MMV) and summarized as follows: (1) highly efficacious, even against drug-resistant parasites (preferably with a new mechanism of action (MoA)); (2) safe, especially for young children and pregnant women; (3) administered orally in three daily doses or less, (4) inexpensive and (5) stable with a long shelf-life under tropical conditions; with the overarching goal to achieve a single-dose cure combination therapy. The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adult and adolescent patients with uncomplicated Plasmodium falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PLATINUM
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 11/09/2023
Actual trial start date 23/01/2024
Anticipated date of last follow up 04/05/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 300
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
CADPT13A12201 N/A
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 Central randomisation by phone/fax Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Cohort A1 INE963 Dose Level 1 INE963 dose level 1 once 1 day One dose of oral INE963 at dose level 1 will be given to the patient 10
Experimental Group Cohort A1 INE963 Dose Level 2 INE963 dose level 2 given once 1 day One dose of oral INE963 at dose level 2 will be given to the patient 10
Experimental Group Cohort A1 INE963 Dose Level 3 INE963 dose level 3 given once 1 day One dose of oral INE963 at dose level 3 will be given to the patient 10
Experimental Group Cohort B1 INE963 and KAE609 Highest safe dose of INE963 from Part A plus KAE609 at a fixed dose given once 1 day A loose combination of INE963 at the highest safe dose from Part A plus KAE609 at a fixed dose given to the patient orally 60
Control Group Cohort B1 Coartem Coartem 80 / 480 mg twice daily for 3 days 3 days Coartem 80 / 480 mg given orally twice daily for 3 days 30 Active-Treatment of Control Group
Experimental Group Cohort B2 KLU156 and KAE609 KLU156 at a fixed dose level and KAE609 at a fixed dose level 1 day A loose combination of KLU156 in sachet form will be given to the patient orally with KAE609 at a fixed dose level 30
Control Group Cohort B2 Coartem Coartem 80 / 480 mg twice daily for 3 days 3 days Coartem 80 / 480 mg given orally to the patient twice daily for 3 days 30 Active-Treatment of Control Group
Experimental Group Cohort C2 KLU156 and KAE609 KLU156 at a fixed dose level and KAE609 at a fixed dose level 1 day A loose combination of KLU156 in sachet form will be given to the patient orally with KAE609 at a fixed dose level 80
Control Group Cohort C2 Coartem Coartem 20 / 120mg twice daily for 3 days 3 days Coartem 20 / 120 mg given orally to the patient twice daily for 3 days 40 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Signed informed consent must be obtained prior to participation in the study Male and female patients ≥18 years of age for Part A, ≥12 years of age for Part B, and ≥2 years and <12 years for Part C at screening Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 5,000 to 150,000 asexual parasite count/μl of blood for P. falciparum for Part A and between 1,000 to 150,000 asexual parasite count/μl of blood for Parts B and C Patients in Part A must weigh between 40 kg and 90 kg. Patients in Part B must weigh between 35 kg and 90 kg at screening. Patients in Part C must weigh at least 10 kg at screening. Patients must be able to swallow oral medications Able to communicate well with the investigator, to understand and comply with the requirements of the study Patients with signs and symptoms of severe/complicated malaria at screening or mixed Plasmodium infection (i.e., infection with more than one malaria species) at screening Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level < 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening Known clinically significant liver disease (e.g., chronic hepatitis, liver cirrhosis (compensated or decompensated), history of hepatitis B or C, hepatitis A or B vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis. Clinical or laboratory evidence of any of the following at screening: AST/ALT > 3 x the upper limit of normal range (ULN), regardless of the level of total bilirubin AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN Total bilirubin > 2 x ULN, regardless of the level of AST/ALT Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening. Pregnant or nursing (lactating) women, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception as outlined in Section 12, and sexually active patients not willing to practice effective contraception. History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker History of familial long QT syndrome or known family history of Torsades de Pointe. Resting heart rate (physical exam or 12 lead ECG) < 50 bpm For full list, please reference protocol section 5.2 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 2 Year(s) 150 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 20/07/2023 Navrongo Local EC NHRCIRB administrator
Ethics Committee Address
Street address City Postal code Country
Navrongo Health Research Centre, box 114 Navrongo NA Ghana
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 Kintampo Health Research Centre
Ethics Committee Address
Street address City Postal code Country
Kintampo Health Research Centre Institutional Ethics Committee KHRC IEC Kintampo NA Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2023 Ghana Health Service Ethics and Review Committee
Ethics Committee Address
Street address City Postal code Country
Ghana Health Service, PMB, Ministries Accra NA Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2023 Makerere University College of Health Sciences School of Biomedical Sciences Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Makerere University College of Health Sciences, P.O. Box 7072, Kampala NA Uganda
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 26/04/2023 Joint Clinical Research Center
Ethics Committee Address
Street address City Postal code Country
Lubowa Hill, Plot 101 Entebbe Road P. O. Box 10005 Kampala NA Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2023 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Plot 6 Kimera Rd, Kampala P.O. BOX 6884 Kampala NA Uganda
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 06/04/2023 Comite National dEthique des Sciences de la vie et de La Sante CNESVS
Ethics Committee Address
Street address City Postal code Country
Boulevard de lUniversite Enceinte CHU Cocody Abidjan NA Cote Divoire
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2023 National Ethics Committee Ministry of Health
Ethics Committee Address
Street address City Postal code Country
P O Box 84 Kigali NA Rwanda
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 dEthique pour la Recherche en Sante CERS
Ethics Committee Address
Street address City Postal code Country
03 BP 7009 Ouagadougou 03 Ouagadogou NA 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
No 17/03/2023 CNER Comite National dEthique pour la Recherche
Ethics Committee Address
Street address City Postal code Country
BP 2217 Libreville Libreville NA Gabon
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2023 CERMEL CEI
Ethics Committee Address
Street address City Postal code Country
BP 242 Lambarene NA Gabon
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 05/06/2023 Kenya Medical Research Institute
Ethics Committee Address
Street address City Postal code Country
PO Box 54840-00200 Nairobi NA Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Part A - Parasite clearance time of oral doses of anti-malarial agents administered as monotherapy in patients with uncomplicated Plasmodium falciparum malaria. PCT is defined as the time from the first positive blood slide at inclusion to the time of the first negative slide followed by two consecutive slides. Day 1 - Day 7
Primary Outcome Parts B and C- cure rate of an anti-malarial agent administered orally as combination therapy versus the standard of care in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR corrected adequate clinical and parasitological response ACPR. ACPR is defined as the absence of parasitemia on Study Day 29 irrespective of axillary temperature, without previously meeting any of the criteria of Early Treatment Failure (ETF) or Late Clinical Failure (LCF) or Late Parasitological Failure (LPF). Day 1 - Day 29
Secondary Outcome Part A - cure rate of an anti-malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR corrected adequate clinical and parasitological response ACPR Day 1 - Day 29
Secondary Outcome Parts B and C - Parasite clearance time of oral doses of anti-malarial agents administered as monotherapy in patients with uncomplicated Plasmodium falciparum malaria Day 1 - Day 7
Secondary Outcome Parts B and C - cure rate of an anti-malarial agent administered orally as combination therapy versus the standard of care in patients with uncomplicated P. falciparum malaria by using polymerase chain reaction PCR uncorrected adequate clinical and parasitological response ACPR Day 1 - Day 29
Secondary Outcome AUClast - Area under the serum concentration-time curve from time zero to the time of last measurable concentration sample time Day 1 - Day 22
Secondary Outcome AUCinf - Area under the concentration time curve from time zero (pre-dose) to infinity. Day 1 - Day 22
Secondary Outcome Cmax - the maximum (peak) observed plasma, blood, serum, or other blood fluid drug concentration after single dose administration. Day 1 - Day 22
Secondary Outcome Tmax - the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration. Day 1 - Day 22
Secondary Outcome T1/2 - the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve. Day 1 - Day 22
Secondary Outcome CL - the total body clearance of drug from the plasma. Day 1 - Day 22
Secondary Outcome Vz/F - the apparent volume of distribution during terminal phase. Day 1 - Day 22
Secondary Outcome Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. Day 1 - Day 43
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre Medical Urbain de Banfora District Sanitaire de Banfora Region Sanitaire des cascade Banfora Burkina Faso
Unite de Recherche Clinique de Nanoro URCN/CMA Centre Muraz CM St Camille de Nanoro 11 BP 218 Ouagadougou Burkina Faso
Formation Sanitaire a Base Pasteur Institute of Ivory Coast Abidjan 01 Cote Divoire
Ayame General Hospital Pasteur Inst of Ivory Coast PO Box 81 Ayame Cote Divoire
Centre de Recherches Medicales de BP 242 Lambarene Gabon
Cermel Sindara Site RN2 Estuaire au Haut Ogooue Sindara Gabon
Navrongo Health Research Centre Behind Navrongo War Memorial Hospital Navrongo Hospital Road PO Box 114 Navrango Ghana
Kintampo Health Research Centre Ministry of HealthNo.2 Health loop Kintampo North Municipality Brong Ahafo Region Kintampo Ghana
Jaramogi Oginga Odinga Hospital Jomo Kenyatta Highway Kaloleni Kisumu Kenya
Creates Research Centre Strathmore University Nairobi City Madraka Estate Ole Sangale Road Nairobi Kenya
Rinda Ubuzima Rwanda Military Hosp CMHS KG 11 Avenue 47 Remera Campus Kigali Rwanda
Infectious Diseases Research Collaboration Tororo Hospital Station Road Tororo Uganda
Joint Clinical Research Centre Plot 101 Upper Lubowa Estates PO Box 10005 Kampala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Novartis Pharma AG Lichtstrasse 35 Basel CH-4056 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharma AG Lichtstrasse 35 Basel CH-4056 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Amanda Nguyen amanda.nguyen@novartis.com +16177687499 220 Massachusetts Avenue
City Postal code Country Position/Affiliation
Cambridge United States of America Clinical Scientist
Role Name Email Phone Street address
Scientific Enquiries William Prince william_t.prince@novartis.com +16177108491 220 Massachusetts Avenue
City Postal code Country Position/Affiliation
Cambridge United States of America TM Profiling Head Global Health
Role Name Email Phone Street address
Principal Investigator TBD TBD tbd@tbd.com 123456789 TBD
City Postal code Country Position/Affiliation
TBD Rwanda Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com. Study Protocol This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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