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

• Status: Completed
• Trial end date: 2021-06-28
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Collaborator: Medicines for Malaria Venture
• Treatments: Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination

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