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

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

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)

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: KAF156

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Srisaket, Thailand, 33140
    • Novartis Investigative Site
  • Tak, Thailand, 63140
    • Novartis Investigative Site
  • Tak, Thailand, 63110
    • Novartis Investigative Site
• Vietnam
  • Hanoi, Vietnam, 10000
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• White NJ, Duong TT, Uthaisin C, Nosten F, Phyo AP, Hanboonkunupakarn B, Pukrittayakamee S, Jittamala P, Chuthasmit K, Cheung MS, Feng Y, Li R, Magnusson B, Sultan M, Wieser D, Xun X, Zhao R, Diagana TT, Pertel P, Leong FJ. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med. 2016 Sep 22;375(12):1152-60. doi: 10.1056/NEJMoa1602250.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 19, 2012
• First Posted (ESTIMATE): December 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: acute malaria, KAF156
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Vivax
• Other Study ID Numbers: CKAF156X2201