Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model

Novartis Pharmaceuticals86 enrolled

Overview

This study is designed to investigate the safety and causal prophylactic efficacy of KAF156 in healthy subjects using a controlled human malaria infection model.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Malaria

Interventions

KAF156DRUG

100 mg tablet, 20 mg tablet, 50 mg tablet

PlaceboDRUG

100 mg tablet, 20 mg tablet, 50 mg tablet

Eligibility

Sex: MALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: \- Healthy male subjects,aged 18 to 40 years of age included and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests Exclusion Criteria: * History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. * Known history or current clinically significant ECG abnormalities or arrhythmias. * Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, or other conditions which could interfere with the interpretation of the study results or compromise the health of the subjects. * Sexually active males must use a condom during intercourse while taking drug and for al least 4 weeks after stopping study medication and should not father a child during this period. * History of malaria or residence in a malaria-endemic area over a period of 6 months before study entry. - Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk or render the subject unable to meet requirements of the protocol. Other protocol-defined inclusion/exclusion criteria may apply.

Locations (1)

Novartis Investigative Site

Seattle, Washington, United States

Outcomes

Primary Outcomes

Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes

The number of subjects that became infected with malaria at each dose

Time frame: From Day 1 to Day 43

Relationship between pharmacokinetics (i.e., Maximum Plasma Concentration [Cmax], Area Under Curve [AUC]) of KAF156 and number of subjects with parasitemia, after oral administration of single descending doses of KAF156 in healthy subjects with CHMI

The exposure-response relationship of KAF156 was explored in a PK/PD model to relate drug exposure to prophylactic efficacy using standard statistical methods such as CART or non-linear regression. Summary statistics were also provided for the malaria incidence rate by cohort and treatment arm

Time frame: From Day 1 to Day 43

Secondary Outcomes

Number of subjects with adverse events, serious adverse events, and death

All information obtained on adverse events will be displayed by arm, treatment, and subject. The number and percentage of subjects with adverse events will be tabulated by body system and preferred term with a breakdown by cohort and treatment.

Time frame: From screening to Day 43

Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

KAF156 plasma concentration data will be listed by arm, subject, and sampling time point. Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate AUCinf