Malaria
Conditions
Keywords
Malaria, KAF156, P. falciparum
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.
Interventions
DRUGKAF156
100 mg tablet, 20 mg tablet, 50 mg tablet
DRUGPlacebo
100 mg tablet, 20 mg tablet, 50 mg tablet
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes | From Day 1 to Day 43 | The number of subjects that became infected with malaria at each dose |
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| 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 | 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 |
| 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 | 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. |
| Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (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 | 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 |
| Number of subjects with adverse events, serious adverse events, and death | 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. |
| Pharmacokinetics of KAF156: Observed maximum plasma concentration (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 | 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 |
| Pharmacokinetics of KAF156: Time to reach the maximum concentration (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 | 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 |
| Parasite growth Kinetics by qRT-PCR | Pre-dose, days 7-23, Day 29, Day 43 | Parasitemia levels as measured by qRT-PCR will be summarized and displayed graphically over time. |
| Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (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 | 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 |
| 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 | 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 |
Countries
United States
Outcome results
None listed