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.: PACTR202012535210091 Date of Approval: 02/12/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Efficacy, safety and tolerability of KAF156 in combination with Lumefantrine Solid Dispersion Formulation (LUM-SDF) in a pediatric population with uncomplicated Plasmodium falciparum malaria
Official scientific title A Phase 2 interventional, multicenter, randomized, open-label study in three age-descending cohorts to evaluate efficacy, safety and tolerability of KAF156 and Lumefantrine-SDF combination, under fasted or fed conditions, in the treatment of acute uncomplicated Plasmodium falciparum Malaria in a pediatric population
Brief summary describing the background and objectives of the trial This study aims to determine the efficacy, safety and tolerability of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in pediatric patients (6 months to < 18 years of age) with uncomplicated P. falciparum malaria. There is an unmet medical need for anti-malarial treatment with a new mechanism of action to reduce the probability of developing resistance, and for a duration shorter than 3 days of treatment and/or reduced pill burden.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) KALUMI
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 15/12/2020
Actual trial start date
Anticipated date of last follow up 15/12/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 224
Actual target sample size (number of participants)
Recruitment status Not yet 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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group KAF156 and Lumefantrine SDF Starting dose in adolescents 12 to <18 years is KAF156 400mg and LUM-SDF 200mg QD 2 Days Treatment given in fasted patients 112
Experimental Group KAF156 and Lumefantrine SDF Starting dose in adolescents 12 to <18 years is KAF156 400mg and LUM-SDF 200mg QD 2 Days Treatment given in fed patients 112
Control Group None Not applicable Not applicable Not applicable 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- In Run-in Cohort: Male and female patients 12 to < 18 years of age, with a body weight ≥ 35.0 kg - In Cohort 1: Male and female patients 2 to < 12 years of age, with a body weight ≥ 10.0 kg - In Cohort 2: Male and female patients 6 months to < 2 years of age, with a body weight ≥ 5.0 kg - Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films - P. falciparum parasitemia of ≥ 1,000 and ≤ 150,000 parasites/μL at the time of pre-screening - Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.0 ºC; or history of fever during the previous 24 hours (at least documented verbally) - The patient and his/her parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned - Mixed Plasmodium infections. - Signs and symptoms of severe malaria - Significant, nonplasmodial co-infections including tuberculosis - Patients with concurrent febrile illnesses - Known relevant liver disease - Major congenital defects - Any confirmed or suspected immunosuppressive or immunodeficient condition 8. Immunosuppressive therapy within 3 months prior to recruitment. - Repeated vomiting or severe diarrhea - Active duodenal ulcer, ulcerative colitis, Crohn’s disease, chronic use of non-steroidal anti-inflammatory drugs - Clinically relevant abnormalities of electrolyte balance which require correction - Anemia - Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the patient in case of participation in the study - Resting QT interval corrected by Fridericia’s formula (QTcF) > 450 ms at screening - Creatinine > 2 x ULN in the absence of dehydration. In case of dehydration, creatinine should be < 2 x ULN after oral/parenteral rehydration - Known chronic underlying disease such as sickle cell disease, and severe cardiac, renal, or hepatic impairment - Known active or uncontrolled thyroid disease - History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval - Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 6 Month(s) 17 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 02/09/2020 Comite de Ethique pour la Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
03 BP 7009 Ouagadougou 03 BP 7009 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome PCR-corrected adequate clinical and parasitological response (ACPR) at Day 29 (Cohorts 1 and 2) Day 29
Secondary Outcome KAF156 PK parameters such as AUC0-24, Tmax and Cmax (Run-in Cohort) Screening and 1h, 3h, 4h, 5h, 6h, 8h, 24h, 25h, 27h, 28, 29h, 30h, 32h, 48h, 72h, 168h post first dose
Secondary Outcome LUM PK parameters such as AUC0-24h, Tmax and Cmax (Run-in Cohort) Screening and 1h, 3h, 4h, 5h, 6h, 8h, 24h, 25h, 27h, 28, 29h, 30h, 32h, 48h, 72h, 168h post first dose
Secondary Outcome Standard safety/tolerability assessments: Adverse events (AE)/serious adverse events (SAE) incidence and severity, laboratory abnormalities and electrocardiogram (ECG) abnormalities Day 1 to Day 43
Secondary Outcome KAF156 and lumefantrine: PK parameters such as AUC0-24h, Cmax (LUM Cmax for Cohorts 1 and 2), C168 h and Tmax 3h, 6h, 24h, 27h, 30h, 48h, 72h, 168h post first dose for patients 6 to less than 12 years, and 6h, 24h, 27h, 30h, 48h, 72h, 168h post first dose in patients 2 to less than 6 years
Secondary Outcome PCR-corrected adequate clinical and parasitological response (ACPR) at Days 15 and 29 (Run-in Cohort) and Day 43, and the uncorrected ACPR at Days 15, 29 and 43. Incidence rate of recrudescence and reinfection. Parasite and fever clearance Times (PCT and FCT). Day 15, Day 29 and Day 43
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Sciences Techniques and Technologies MRTC, FMOS-FAPH, Point G Bamako BP 1805 Mali
Groupe de Recherche Action en Sante 06 BP 10248 Ouagadougou 06 Ouagadougou BP 10248 Burkina Faso
Institut des Sciences et Techniques 540 Avenue de Sya, 01 Bobo Dioulasso BP 2779 Burkina Faso
Centre de Recherches Medicales de Lambarene Centre de Recherches Medicales de Lambarene Lambarene BP 242 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership P.O. Box 93015 The Hague 2509 AA Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharma AG Fabrikstrasse 2 Basel CH-4056 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Medicines for Malaria Venture 20 Route de Pre Bois Geneva 1215 Switzerland
WANECAM 2 Consortium MRTC, FMOS-FAPH, Point G Bamako BP 1805 Mali
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Issaka Sagara isagara@icermali.org +22376459079 MRTC, FMOS-FAPH, Point G
City Postal code Country Position/Affiliation
Bamako BP 1805 Mali University of Sciences Techniques and Technologies Bamako
Role Name Email Phone Street address
Public Enquiries Novartis Pharma AG novartis.email@novartis.com 41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
Role Name Email Phone Street address
Scientific Enquiries Novartis Pharma AG novartis.email@novartis.com 41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com. Study Protocol This trial data is currently available according to the process described on www.clinicalstudydatarequest.com. 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 expert panel on the basis of scientific merit.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.clinicalstudydatarequest.com No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information