Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

• Register: ClinicalTrials.gov
• Last refreshed on: 20 September 2021
• Main ID: NCT03167242
• Date of registration: 19/05/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
• Scientific title: 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
• Date of first enrolment: August 2, 2017
• Target sample size: 484
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03167242
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Burkina Faso, Côte D'Ivoire, Gabon, Gambia, India, Kenya, Mali, Mozambique, Thailand, Uganda, Vietnam

Contacts

• Name: Study Director
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

- Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.

- 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).

- Axillary temperature = 37.5 ºC or oral/tympanic/rectal temperature = 38.3 ºC; or
similar history of fever during the previous 24 hours (history of fever must be
documented).

- 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.

Exclusion Criteria:

- Mixed Plasmodium infections.

- Signs and symptoms of severe malaria according to WHO (World Health Organization) 2015
criteria unless characterized by high parasitaemia only.

- Patients with concurrent febrile illnesses (e.g., typhoid fever).

- Severe 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 per day.

- Pregnant or nursing (lactating) women.

- Clinically relevant abnormalities of electrolyte balance which require correction,
e.g., hypokalemia, hypocalcemia or hypomagnesemia.

- Anemia (Hemoglobin level < 8 g/dL).

- 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 (heart rate-corrected QT) interval, such
as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or
severe heart disease.

- 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. 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:

- AST/ALT > 2 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



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acute Uncomplicated Plasmodium Falciparum Malaria

Intervention(s)

Drug: Coartem

Drug: KAF156 and LUM-SDF

Primary Outcome(s)

PCR-corrected adequate clinical and parasitological response (ACPR) [Time Frame: Day 28 post-dose]

Secondary Outcome(s)

Incidence rate of recrudescence and reinfection [Time Frame: Days 14, 28 and 42 post-dose]

Time after administration of a drug when the maximum plasma concentration is reached (Tmax) [Time Frame: Up to Day 15 post-dose]

Maximum Peak Observed Concentration (Cmax) [Time Frame: Up to Day 15 post-dose]

Adverse events (AE) incidence and severity, liver and kidney function tests and electrocardiogram (ECG) abnormalities [Time Frame: Up to Day 42 post-dose]

Area Under the Curve (AUC) [Time Frame: Up to Day 15 post-dose]

PCR-corrected ACPR [Time Frame: Days 14 and 42 post-dose]

Half-life (T½) [Time Frame: Up to Day 15 post-dose]

Parasite and fever clearance times [Time Frame: Up to Day 42 post-dose]

PCR-uncorrected ACPR [Time Frame: Days 14, 28 and 42 post-dose]

Proportion of patients with parasitaemia [Time Frame: 12, 24 and 48 hours after treatment]

Secondary ID(s)

CKAF156A2202

2020-003284-25

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Medicines for Malaria Venture