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

NCT04072302 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CKAF156X2202
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Malaria; KAF156; P. falciparum

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

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

  From screening to Day 43

• 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

• 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

• 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

• 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

Study Arms (12)

KAF156 800 mg pre-challenge

EXPERIMENTAL

Single dose 800 mg KAF156 oral administration in healthy subjects, prior to exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 800 mg pre-challenge

PLACEBO COMPARATOR

Single dose 800 mg placebo oral administration in healthy subjects, prior to exposure to P. falciiparum sporozoite-infected mosquitos

Drug: Placebo

KAF156 800 mg post-challenge

EXPERIMENTAL

Single dose 800 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 800 mg post-challenge

PLACEBO COMPARATOR

Single dose 800 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: Placebo

KAF156 300 mg post-challenge

EXPERIMENTAL

Single dose 300 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 300 mg post-challenge

PLACEBO COMPARATOR

Single dose 300 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: Placebo

KAF156 100 mg post-challenge

EXPERIMENTAL

Single dose 100 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 100 mg post-challenge

PLACEBO COMPARATOR

Single dose 100 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: Placebo

KAF156 20 mg post-challenge

EXPERIMENTAL

Single dose 20 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 20 mg post-challenge

PLACEBO COMPARATOR

Single dose 20 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: Placebo

KAF156 50 mg post-challenge

EXPERIMENTAL

Single dose 50 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: KAF156

Placebo 50 mg post-challenge

PLACEBO COMPARATOR

Single dose 50 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos

Drug: Placebo

Interventions

KAF156 DRUG

100 mg tablet, 20 mg tablet, 50 mg tablet

KAF156 100 mg post-challenge; KAF156 20 mg post-challenge; KAF156 300 mg post-challenge; KAF156 50 mg post-challenge; KAF156 800 mg post-challenge; KAF156 800 mg pre-challenge

Placebo DRUG

100 mg tablet, 20 mg tablet, 50 mg tablet

Placebo 100 mg post-challenge; Placebo 20 mg post-challenge; Placebo 300 mg post-challenge; Placebo 50 mg post-challenge; Placebo 800 mg post-challenge; Placebo 800 mg pre-challenge

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 32644127 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

ganaplacide

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: August 28, 2019
• Study Start: September 15, 2014
• Primary Completion: November 29, 2017
• Study Completion: November 29, 2017
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (1)