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

Browse trials for

• Malaria 1,299

Keywords

• Malaria
• KAF156
• P. falciparum

Malaria

1,299 studies on the registry are indexed under Malaria; 86 are open to participants now.

This study's enrollment of 86 is below the median of 220 across 1,027 interventional studies indexed under Malaria.

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Study arms

• Experimental
  KAF156 800 mg pre-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 800 mg pre-challenge

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

  Drug: Placebo

• Experimental
  KAF156 800 mg post-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 800 mg post-challenge

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

  Drug: Placebo

• Experimental
  KAF156 300 mg post-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 300 mg post-challenge

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

  Drug: Placebo

• Experimental
  KAF156 100 mg post-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 100 mg post-challenge

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

  Drug: Placebo

• Experimental
  KAF156 20 mg post-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 20 mg post-challenge

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

  Drug: Placebo

• Experimental
  KAF156 50 mg post-challenge

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

  Drug: KAF156

• Placebo comparator
  Placebo 50 mg post-challenge

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

  Drug: Placebo

Interventions

• DrugKAF156

  100 mg tablet, 20 mg tablet, 50 mg tablet

• DrugPlacebo

  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

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

   Time frame: From Day 1 to Day 43

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

   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

   Time frame: From Day 1 to Day 43

Secondary outcomes

1. 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.

   Time frame: From screening to Day 43

2. 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

   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

3. 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

   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

4. 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

   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

5. 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.

   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

6. 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

   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

7. 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

   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

8. 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

   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

9. 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

   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

10. Parasite growth Kinetics by qRT-PCR

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

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

Publications

• 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. PubMed 32644127 ↗