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

Launched by NOVARTIS PHARMACEUTICALS · May 23, 2017

Keywords

ClinConnect Summary

This was a Phase 2 multi-center and open-label study with a single cohort pharmacokinetic (PK) Run-in Part followed by 2 randomized parallel-group parts, Part A and Part B, in adults and children with confirmed and uncomplicated Plasmodium falciparum malaria. Each part (PK Run-in, Part A and Part B) had the same design structure: A screening phase of up to 24 hours where participants were evaluated for eligibility and randomized (Part A and B) into different cohorts. A treatment phase of up to 3 days where participants were treated for 1, 2 or 3 consecutive days. Finally, participants were ...

Gender

ALL

Eligibility 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