Clinical Trials Register

Summary
EudraCT Number:	2021-003583-27
Sponsor's Protocol Code Number:	CKAF156A2203
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2024-10-15
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2021-003583-27

A.3

Full title of the trial

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 in the treatment of acute uncomplicated Plasmodium falciparum Malaria in a pediatric population

Étude interventionnelle de phase II, multicentrique, randomisée et en ouvert dans trois cohortes d’âge décroissant visant à évaluer l’efficacité, la sécurité et la tolérabilité de la combinaison KAF156 et luméfantrine-SDF, dans le traitement du paludisme aigu non compliqué à Plasmodium falciparum dans une population pédiatrique

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy, safety and tolerability of KAF156 in combination with LUM-SDF in pediatric population with uncomplicated Plasmodium falciparum malaria

Efficacité, sécurité et tolérabilité du KAF156 en association avec la LUM-SDF dans une population pédiatrique atteinte de paludisme non compliqué à Plasmodium falciparum

A.4.1

Sponsor's protocol code number

CKAF156A2203

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Medicines for Malaria Venture
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	European and Developing Countries Clinical Trials Partnership
B.4.2	Country	South Africa
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Disclosure Office
B.5.3	Address:
B.5.3.1	Street Address	Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41613241111
B.5.6	E-mail	novartis.email@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	RIAMET® Dispersible
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma Schweiz AG
D.2.1.2	Country which granted the Marketing Authorisation	Switzerland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	KAF156
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ganaplacide
D.3.9.2	Current sponsor code	CKAF156A2203
D.3.9.4	EV Substance Code	SUB193571
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lumefantrine-SDF
D.3.2	Product code	LUM566
D.3.4	Pharmaceutical form	Granules for oral suspension in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lumefantrine
D.3.9.1	CAS number	82186-77-4
D.3.9.3	Other descriptive name	Lumefantrine Solid Dispersion Formulation
D.3.9.4	EV Substance Code	SUB08618MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	240
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Plasmodium Falciparum Malaria

E.1.1.1

Medical condition in easily understood language

Uncomplicated malaria

E.1.1.2

Therapeutic area

Diseases [C] - Parasitic Diseases [C03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10035500
E.1.2	Term	Plasmodium falciparum infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the efficacy of KAF156 combined with LUM-SDF compared to Coartem® (non-inferiority trial) for the treatment of uncomplicated malaria caused by P. falciparum in children 6 months to < 12 years old

E.2.2

Secondary objectives of the trial

1) To investigate the effect of food on lumefantrine bioavailability in patients 12 to < 18 years old (Run-in Cohort).
2) To investigate the effect of food on KAF156 bioavailability in patients 12 to < 18 years old (Run-in Cohort).
3) To evaluate safety and tolerability of KAF156/LUM-SDF in pediatric patients (6 months to <18 years old).
4) To assess PK of KAF156 and lumefantrine in pediatric patients (6 months to <12 years).
5) To evaluate the efficacy of KAF156 combined with LUM-SDF by assessing uncorrected and corrected adequate clinical and parasitological response (ACPR) at different time points as well as fever- and parasite- clearance times.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• 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 for Run-in Cohort
• P. falciparum parasitemia of ≥ 1,500 and ≤ 150,000 parasites/μL at the time of pre-screening for Cohorts 1 and 2
• 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)
• Written informed consent has been obtained from parent / legal guardian before any assessment is performed. If the parent / legal guardian is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines
• 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.

E.4

Principal exclusion criteria

• Mixed Plasmodium infections as per light microscopy results
• Signs and symptoms of severe malaria according to the World Health Organization (WHO 2015)
• Patients with concurrent febrile illnesses (e.g., typhoid fever, known or suspected COVID19)
• Repeated vomiting (defined as more than 3 times in the 24 hours prior to inclusion in the study) or severe diarrhea (defined as more than 3 watery stools in the 24 hours prior to inclusion in the study)
• Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
• Anemia (hemoglobin level < 7 g/dL)
• Patients of child bearing potential, defined as all girls post first menarche (except for Run-in Cohort)
• Pregnant or nursing (lactating) patients
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., HIV patients on ART therapy or TB patients on treatment), or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient’s medical history and/or clinical or laboratory evidence of any of the following:
• Aspartate aminotransferase (AST)/alanine aminotransferase (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
• Patients with prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is unknown)
• History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease.

E.5 End points

E.5.1

Primary end point(s)

PCR-corrected adequate clinical and parasitological response (ACPR) at Day 29 (i.e., 28 days post-dose)

E.5.1.1

Timepoint(s) of evaluation of this end point

On E.5.1

E.5.2

Secondary end point(s)

• KAF156 PK parameters such as AUC, Tmax and Cmax (Run-in Cohort).
• LUM PK parameters such as AUC, Tmax and Cmax (Run-in Cohort).
• Standard safety/tolerability assessments: Adverse events (AE)/serious adverse events (SAE) incidence and severity, laboratory abnormalities and electrocardiogram (ECG) abnormalities.
• KAF156 and lumefantrine: PK parameters such as AUC, Cmax (LUM Cmax for Cohorts 1 and 2), C168 h and Tmax.

E.5.2.1

Timepoint(s) of evaluation of this end point

On E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Non-inferiority

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Burkina Faso

Congo, The Democratic Republic of the

Gabon

Mali

Côte d’Ivoire

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS: 28.08.2024

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

295

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

F.1.1.5.1

Number of subjects for this age range:

140

F.1.1.6

Adolescents (12-17 years)

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients under 18

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Minors

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

220

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Burkina Faso

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