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CTRI Number  CTRI/2020/10/028535 [Registered on: 21/10/2020] Trial Registered Prospectively
Last Modified On: 26/07/2022
Post Graduate Thesis   
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Efficacy and safety of KAF156 in combination with LUM-SDF in adults and children with uncomplicated Plasmodium falciparum malaria 
Scientific Title of Study   A Phase 2 interventional, multicenter, randomized open label study to determine the effective and tolerable dose of KAF156 and Lumefantrine Solid Dispersion Formulation in combination, given once daily for 1, 2 and 3 days to adults and children with uncomplicated Plasmodium falciparum malaria 
Trial Acronym  - 
Secondary IDs if Any  
Secondary ID  Identifier 
CKAF156A2202 Version 3 dated 13-Apr-2018  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai

Mumbai
MAHARASHTRA
400 051
India 
Phone  02250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Scientific Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai

Mumbai
MAHARASHTRA
400 051
India 
Phone  02250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Public Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai

Mumbai
MAHARASHTRA
400 051
India 
Phone  02250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Source of Monetary or Material Support  
Novartis Pharma AG, CH-4002 Basel, Switzerland. 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd 
Address  Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai – 400 051 Maharashtra,INDIA.  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Burkina Faso
Gabon
Gambia
India
Kenya
Mali
Mozambique
Thailand
Uganda
Viet Nam  
Sites of Study
Modification(s)  
No of Sites = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Nirmal Choraria  Nirmal Hospital Pvt. Ltd.  Ring Road, Surat, Gujarat 395002, India
Surat
GUJARAT 		 9825142549

nirmal_choraria@yahoo.com 
Dr Amar Verma  Rajendra Institute of Medical Sciences  Bariatu, Ranchi, Jharkhand 834009, India
Ranchi
JHARKHAND 		 9835527473

manojdas2@gmail.com 
Dr Rajesh SM  Wenlock District Hospital  Hampankatta, Mangaluru, Karnataka 575001, India
Bangalore
KARNATAKA 		 9343434344

majorrajeshsm@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Manipal University Ethics Committee_Dr Rajesh SM  Submittted/Under Review 
Nirmal Hospital Ethics committee  Approved 
Rajendra Institute of Medical Sciences_Dr Verma  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: B95-B97||Bacterial and viral infectious agents,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Part A  KAF156 200mg + LUM-SDF 480mg 3 days Oral dose 
Intervention  Part A  KAF156 400mg + LUM 960mg 2 days Oral 
Intervention  Part A  KAF156 400mg + LUM-SDF 480mg 3 days Oral dose 
Intervention  Part A  KAF156 400mg + LUM-SDF 960 mg, 3 days oral dose 
Intervention  Part A  KAF156 400mg + LUM-SDF 960mg 1 Day oral dose 
Intervention  Part A  KAF156 800mg + LUM-SDF 960 mg 1 day oral 
Comparator Agent  Part A  lumefantrine 80/480mg 
 
Inclusion Criteria  
Age From  2.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1 PK Run-in Part and Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg
Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included
2 Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films (refer to the laboratory manual for details)
3 P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/µL at the time of pre-screening (i.e., Study Visit 1)
4 Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or similar history of fever during the previous 24 hours (history of fever must be documented)
5 Negative pregnancy test for women of child bearing potential (WOCBP)
6 Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines
7 The patient or his/her parent/legal guardian (in case of pediatric patients) is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned


 
 
ExclusionCriteria 
Details  1 Mixed Plasmodium infections
2 Signs and symptoms of severe malaria according to WHO 2015 criteria unless
characterized by high parasitaemia only
3 Patients with concurrent febrile illnesses (e.g., typhoid fever)

4 Active infections including tuberculosis
5 History of, or current alcohol misuse/abuse defined as five or more drinks on the same
occasion on each of 5 or more days in the past 30 days
6 Known relevant liver disease e.g. chronic hepatitis, cirrhosis, compensated or
decompensated, history of hepatitis B or C, hepatitis B or A vaccination in last 3 months,
known gallbladder or bile duct disease, acute or chronic pancreatitis
7 Any confirmed or suspected immunosuppressive or immunodeficient condition,
including human immunodeficiency virus (HIV) infection
8 Women of child bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for the duration of the study. Highly effective contraception methods
include
ï‚· Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) total hysterectomy or tubal ligation at least six weeks before taking
investigational drug. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the
study, the vasectomized male partner should be the sole partner for that patient
9 Active duodenal ulcer, ulcerative colitis, Crohn’s disease, chronic (i.e., > 2 weeks) use
of non-steroidal anti-inflammatory drugs (NSAIDs)
10 Clinically relevant abnormalities of electrolyte balance which require correction, e.g hypokalemia, hypocalcemia or hypomagnesemia.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
The primary objective of this study is to determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by P. falciparum.  PCR-corrected adequate clinical and
parasitological response (ACPR) at Day 29 (i.e., 28 days post-dose) in Parts A
and B. 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the safety and tolerability of KAF156/LUM-SDF.  Standard safety/tolerability
assessments: AE incidence and
severity, liver and kidney function tests and electrocardiogram (ECG)
abnormalities. 
To further assess the effect of treatment
with KAF156/LUM-SDF by assessing
uncorrected ACPR and corrected ACPR
at additional time points, as well asfever- and parasite clearance times. 		 PCR-Uncorrected ACPR at Days 15, 29 and 43 (i.e., 14, 28 and 42 days postdose).
PCR-corrected ACPR at Days 15 and 43 (i.e 14 and 42 days post-dose)
Incidence rate of recrudescence and
reinfection at Days 15, 29 and 43
Parasite and Fever Clearance Times
(PCT and FCT).
Proportion of patients with parasitaemia
at 12, 24, and 48 hours after treatment. 
To assess the key PK parameters of KAF156 and lumefantrine.  PK assessments 
 
Target Sample Size   Total Sample Size="500"
Sample Size from India="50" 
Final Enrollment numbers achieved (Total)= "2"
Final Enrollment numbers achieved (India)="496" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   07/12/2020 
Date of Study Completion (India) 22/05/2021 
Date of First Enrollment (Global)  17/11/2017 
Date of Study Completion (Global) 28/06/2021 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Purpose of the study :

This study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated P. falciparum malaria. There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance,and for duration shorter than 3 days of treatment and/or reduced pill burden.


 
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