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

Phase 1

Completed

• Conditions: Malaria
• Interventions: Drug: KAF156; Drug: Placebo

• Registration Number: NCT04072302
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-15
• Primary Completion: 2017-11-29
• Study Completion: 2017-11-29
• Status Verified: 2019-08
• Study First Submitted: 2019-08-20
• Study First Submitted QC: 2019-08-26
• Last Update Submitted: 2019-08-26
• Study First Posted: 2019-08-28
• Last Update Posted: 2019-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 86

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KAF156 20 mg post-challenge	KAF156	Single dose 20 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Placebo 20 mg post-challenge	Placebo	Single dose 20 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
KAF156 50 mg post-challenge	KAF156	Single dose 50 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
KAF156 800 mg pre-challenge	KAF156	Single dose 800 mg KAF156 oral administration in healthy subjects, prior to exposure to P. falciparum sporozoite-infected mosquitos
Placebo 800 mg pre-challenge	Placebo	Single dose 800 mg placebo oral administration in healthy subjects, prior to exposure to P. falciiparum sporozoite-infected mosquitos
KAF156 800 mg post-challenge	KAF156	Single dose 800 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Placebo 800 mg post-challenge	Placebo	Single dose 800 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
KAF156 300 mg post-challenge	KAF156	Single dose 300 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Placebo 300 mg post-challenge	Placebo	Single dose 300 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
KAF156 100 mg post-challenge	KAF156	Single dose 100 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Placebo 100 mg post-challenge	Placebo	Single dose 100 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Placebo 50 mg post-challenge	Placebo	Single dose 50 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Primary Outcome Measures

Name	Time	Method
Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes	From Day 1 to Day 43	The number of subjects that became infected with malaria at each dose
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	From Day 1 to Day 43	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

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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
Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 AUClast
Pharmacokinetics of KAF156: Terminal elimination half life (T1/2)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 T1/2.
Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (Vz/F)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 Vz/F
Pharmacokinetics of KAF156: Observed maximum plasma concentration (Cmax)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 Cmax
Pharmacokinetics of KAF156: Time to reach the maximum concentration (Tmax)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 Tmax
Parasite growth Kinetics by qRT-PCR	Pre-dose, days 7-23, Day 29, Day 43	Parasitemia levels as measured by qRT-PCR will be summarized and displayed graphically over time.
Number of subjects with adverse events, serious adverse events, and death	From screening to Day 43	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.
Pharmacokinetics of KAF156: Area under teh plasma concentration-time curve from time zero to time 24 h (AUC0-24)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 AUC0-24
Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (CL/F)	Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours	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 CL/F

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 Seattle, Washington, United States