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NCT Number: NCT04072302

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

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

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Key information

Conditions

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

Age range

18 year–40 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site

Seattle, Washington, 98109, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

KAF156

Drug

100 mg tablet, 20 mg tablet, 50 mg tablet

Placebo

Drug

100 mg tablet, 20 mg tablet, 50 mg tablet

Primary outcomes

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

    Time frame: From Day 1 to Day 43

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

  2. 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

    Time frame: 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 outcomes

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

    Time frame: 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.

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

    Time frame: 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

  3. Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

    Time frame: 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

  4. Pharmacokinetics of KAF156: Area under teh plasma concentration-time curve from time zero to time 24 h (AUC0-24)

    Time frame: 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

  5. Pharmacokinetics of KAF156: Terminal elimination half life (T1/2)

    Time frame: 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.

  6. Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (CL/F)

    Time frame: 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

  7. Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (Vz/F)

    Time frame: 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

  8. Pharmacokinetics of KAF156: Observed maximum plasma concentration (Cmax)

    Time frame: 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

  9. Pharmacokinetics of KAF156: Time to reach the maximum concentration (Tmax)

    Time frame: 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

  10. Parasite growth Kinetics by qRT-PCR

    Time frame: Pre-dose, days 7-23, Day 29, Day 43

    Parasitemia levels as measured by qRT-PCR will be summarized and displayed graphically over time.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Aug 28, 2019
Registry last updated
Aug 28, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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