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

Malaria Clinical Trial

Official title:

A Two-part, Randomized, Double-blind, Placebo-controlled, Single-center Study to Evaluate the Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04072302
• Other study ID #: CKAF156X2202
• Status: Completed
• Phase: Phase 1
• Start date: September 15, 2014
• Est. completion date: November 29, 2017

Study information

• Verified date: August 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: November 29, 2017
• Est. primary completion date: November 29, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• KAF156
100 mg tablet, 20 mg tablet, 50 mg tablet
• Placebo
100 mg tablet, 20 mg tablet, 50 mg tablet

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	From Day 1 to Day 43
Primary	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	From Day 1 to Day 43
Secondary	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.	From screening to Day 43
Secondary	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	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
Secondary	Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)	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	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
Secondary	Pharmacokinetics of KAF156: Area under teh plasma concentration-time curve from time zero to time 24 h (AUC0-24)	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	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
Secondary	Pharmacokinetics of KAF156: Terminal elimination half life (T1/2)	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.	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
Secondary	Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (CL/F)	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	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
Secondary	Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (Vz/F)	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	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
Secondary	Pharmacokinetics of KAF156: Observed maximum plasma concentration (Cmax)	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	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
Secondary	Pharmacokinetics of KAF156: Time to reach the maximum concentration (Tmax)	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	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
Secondary	Parasite growth Kinetics by qRT-PCR	Parasitemia levels as measured by qRT-PCR will be summarized and displayed graphically over time.	Pre-dose, days 7-23, Day 29, Day 43