Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Study Overview
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Brief Summary
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This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with P. vivax or P. falciparum infection after 3 day dosing with KAF156 at 400 mg/day (Part 1) and single dosing with KAF156 at 800mg (Part 2)

Official Title
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A Proof-of-concept, Open Label Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Conditions
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Malaria

Intervention / Treatment
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* Drug: KAF156


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Male and female patients aged 20 to 60 years;Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg. Exclusion Criteria: Patients with signs and symptoms of severe/complicated malaria Infection with more than one parasite species Women of child-bearing potential; pregnant or nursing women Those who have taken any anti-malarial treatment in the preceding 14 days or other investigational drugs within 30 days or 5 half-lives

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - Cohort 1: P. vivax: KAF156 400mg QD<br>Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days. | Drug: KAF156<br>* KAF156 was supplied as tablets for oral use.<br>|
| Experimental: Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD<br>Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days. | Drug: KAF156<br>* KAF156 was supplied as tablets for oral use.<br>|
| Experimental: Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose<br>Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg. | Drug: KAF156<br>* KAF156 was supplied as tablets for oral use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Parasite Clearance | Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments. | Day 5 | 
| 28-day Cure Rate - Part 2 | 28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC)0-24h - Part 1 | AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose was taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Days 1 and 3 | 
| Maximum Concentration (Cmax) - Part 1 | Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Days 1 and 3 | 
| Time to Maximum Concentration (Tmax) - Part 1 | Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Days 1 and 3 | 
| Area Under the Curve (AUC)Last - Part 1 | AUClast was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| Area Under the Curve (AUC)Inf - Part 1 | AUCinf was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| Half-life (T1/2) - Part 1 | T1/2 was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| Clearance (CL/F ) - Part 1 | CL/F was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1 | Vz/F was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1 | Racc was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 3 | 
| AUC0-24h - Part 2 | AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. | Day 1 | 
| AUC0-48h - Part 2 | AUC0-48h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 1 | 
| AUClast - Part 2 | AUClast was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose | Day 1 | 
| AUCinf - Part 2 | AUCinf was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose | Day 1 | 
| Cmax - Part 2 | Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. | Day 1 | 
| Tmax - Part 2 | Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. | Day 1 | 
| T1/2 - Part 2 | T1/2 was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 1 | 
| CL/F - Part 2 | CL/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 1 | 
| Vz/F - Part 2 | Vz/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute malaria, KAF156