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.: PACTR201801002894101 Date of Approval: 20/12/2017
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Safety of KAE609 in Adults With Uncomplicated Plasmodium Falciparum Malaria.
Official scientific title A Phase 2, multi-center, randomized, open-label, dose escalation study to determine safety of single (QD) and multiple (3 QD) doses of KAE609, given to adults with uncomplicated Plasmodium falciparum malaria
Brief summary describing the background and objectives of the trial KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses. This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients. Condition: Malaria Intervention: Drug: KAE609 Drug: Coartem Phase: Phase 2 Trial objective ¿ Primary Objective(s) The primary objective of this study is to characterize hepatic safety aspects of single- and multiple ascending doses of KAE609 in adult malaria patients. ¿ Secondary Objectives 1.To evaluate overall safety and tolerability of KAE609. 2.To assess key pharmacokinetic (PK) parameters following treatment with KAE609. 3.To assess the efficacy of KAE609 in patients with uncomplicated falciparum malaria. 4.To assess recrudescence after single and multiple doses of KAE609.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CKAE609A2202
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Other
Anticipated trial start date 13/11/2017
Actual trial start date 16/11/2017
Anticipated date of last follow up 14/05/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 150
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://clinicaltrials.gov/ct2/show/NCT03334747?term=KAE609&rank=4
Secondary Ids Issuing authority/Trial register
NCT03334747 ClinicalTrials.gov
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 randomisation using a randomisation table created by a computer software program Central randomisation by phone/fax Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Simple randomisation using a randomisation table created by a computer software program 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 Cohort 1_Treatment arm 1 KAE609 10mg once daily 1 day KAE609 10
Control Group Active comparator treatment arm 2: coartem control Cohort 1_treatment arm 2: coartem twice daily 3 days Coartem 10 Active-Treatment of Control Group
Experimental Group Treatment arm 3: KAE609 25 mg SD Cohort 2_treatment arm 3 25 mg once daily 1 day KAE609 10
Experimental Group Cohort 2: Treatment arm 4 - KAE609 10mg 10mg QD 3 days KAE609 Exploration of different doses to establish safety profile 10
Control Group Cohort 2: Treatment arm 4 Coartem BID 3 days Coartem 10 Active-Treatment of Control Group
Experimental Group Cohort 3: Treamtent arm 6 KAE609 50mg QD 50mg once a day 1 day KAE609: different doses to establish safety profile 20
Experimental Group Cohort 3: Treatment arm 7 25 mg once daily 3 days KAE609 different doses to establish safety profile 20
Control Group Cohort 3: Treatment arm 8 Coartem twice a day 3 days Coartem control 10 Active-Treatment of Control Group
Experimental Group Cohort 4: Treatment arm 9: KAE609 75 mg one daily 1 day KAE609 different doses to establish safety provile 20
Experimental Group Cohort 4: Treatment arm 10. KAE 609 50mg once daily 3 days KAE609 different doses to establish safety profile 20
Control Group Cohort 4: Treatment arm 11. Coartem Coartem twice a day 3 days Coartem control 10 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿Male and female patients ¿ 18 years with a body weight ¿ 45 kg. ¿Microscopic confirmation of acute uncomplicated P. falciparum using by Giemsa-stained thick film. ¿P. falciparum parasitaemia of 500 to 50 000 parasites/¿L. ¿Axillary temperature ¿ 37.5ºC or oral/tympanic/rectal temperature ¿ 38.0ºC; or history of fever during the previous 24 hours. ¿Written informed consent must be obtained before any study assessment is performed. If the patient is unable to write, then a witnessed consent according to local ethical standards is permitted. ¿ Mixed Plasmodiun infections. ¿ Signs and symptoms of severe malaria according to World Health Organization (WHO) 2016 criteria (WHO 2016). ¿ Known liver abnormalities, liver cirrhosis (compensated or decompensated), known active or history of hepatitis B or C (testing not required), known gallbladder or bile duct disease, acute or chronic pancreatitis. ¿ Clinical or laboratory evidence of any of the following: o AST/ALT > 1.5 x the upper limit of normal range (ULN), regardless of the level of total bilirubin o AST/ALT > 1.0 and ¿ 1.5 x ULN and total bilirubin is > ULN o Total bilirubin > 2 x ULN, regardless of the level of AST/ALT ¿ History of photodermatitis/increased sensitivity to sun. ¿Pregnant or nursing (lactating) women. ¿Known disturbances of electrolyte balance, e.g. hypokalemia, hypocalcemia or hypomagnesemia. ¿Moderate to severe anemia(Hemoglobin level <8 g/dL). 18 Year(s) 100 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 08/08/2017 Faculty of Medicine, Pharmacy and Odontostomatology Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Univ of Science, Techniques and Technologies of Bamako Bamako BP1805 Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome At least 2 CTCAE grades increase from baseline in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the 4 week study period ¿ 2 Grade (CTCAE grades) increase from baseline (at any time point during the study) Up to day 29 post dose
Secondary Outcome Recrudescence Time Frame: Up to day 29 post dose ]
Secondary Outcome Polymerase Chain Reaction (PCR) corrected Clinical and Parasitological Cure Time Frame: 15 and 29 days post dose
Secondary Outcome Parasite Clearance Time Up to Day 29
Secondary Outcome Proportion of patients with parasitaemia At 12, 24 and 48 hours post dose
Secondary Outcome Maximum Peak Observed Concentration (Cmax) Up to day 15 post dose
Secondary Outcome Area under the curve (AUC) Up to day 15 post dose
Secondary Outcome Time after administration of a drug when the maximum plasma concentrations is reached (Tmax) Up to day 15 post dose
Secondary Outcome Half-life (T½) Up to Day 15 post dose
Secondary Outcome Fever clearance time up to Day 29
Secondary Outcome Uncorrected Adequate Clinical and Parasitological Response 15 and 29 days post dose
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Sotuba Malaria Research and Training Center Malraia Research and Training Centre (MRTC Sotuba Mali
University Clinical Research Center Point- G National Hospital Bamako Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
Novartis Pharma AG Lichtstrasse 35 Basel CH4056 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharma AG Lichtstrasse 35 Basel CH4056 Switzerland Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Wellcome Trust Gibbs Building 215 Euston Road London NW12BE United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Abraham Rexford Oduro Abraham.Oduro@navrongo-hrc.org +233382122380; _233244593231 Ghana Navrongo Health Research Centre, Behind War Memorial Hospital, Navrongo Hospital Road
City Postal code Country Position/Affiliation
Navrongo -UE/R Ghana Director Navrongo Health Research Centre, Navrongo
Role Name Email Phone Street address
Principal Investigator Kwaku Poku Asante kwakupoku.asante@kintampo-hrc.org +233352097602 Ghana Kintampo Health Research Centre, Ministry of Health
City Postal code Country Position/Affiliation
Kintampo-North, Brong-Ahafo Ghana AG. Director, Kintampo Health Research Centre
Role Name Email Phone Street address
Public Enquiries Preetam Gandhi preetam.gandhi@novartis.com +41 613240806; +41 796181782 Established Medicine WSJ. 204.4.100.62 Novartis Pharma AG
City Postal code Country Position/Affiliation
Basel CH-4002 Switzerland Medical Director
Role Name Email Phone Street address
Scientific Enquiries Preetam Gandhi preetam.gandhi@novartis.com +41 613240806; +41 796181782 Established Medicine WSJ. 204.4.100.62 Novartis Pharma AG
City Postal code Country Position/Affiliation
Basel CH-4002 Switzerland Medical Director
REPORTING
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