Clinical trial NCT04072302: Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: Malaria
KAF156
P. falciparum
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 86
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes
timeFrame: From Day 1 to Day 43
measure: 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
timeFrame: From Day 1 to Day 43
Secondary outcomes:
measure: Number of subjects with adverse events, serious adverse events, and death
timeFrame: From screening to Day 43
measure: Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Area under teh plasma concentration-time curve from time zero to time 24 h (AUC0-24)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Terminal elimination half life (T1/2)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (CL/F)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (Vz/F)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Observed maximum plasma concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetics of KAF156: Time to reach the maximum concentration (Tmax)
timeFrame: 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
measure: Parasite growth Kinetics by qRT-PCR
timeFrame: Pre-dose, days 7-23, Day 29, Day 43
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Kublin JG, Murphy SC, Maenza J, Seilie AM, Jain JP, Berger D, Spera D, Zhao R, Soon RL, Czartoski JL, Potochnic MA, Duke E, Chang M, Vaughan A, Kappe SHI, Leong FJ, Pertel P, Prince WT; KAF156 Study Team. Safety, Pharmacokinetics, and Causal Prophylactic Efficacy of KAF156 in a Plasmodium falciparum Human Infection Study. Clin Infect Dis. 2021 Oct 5;73(7):e2407-e2414. doi: 10.1093/cid/ciaa952.