Phase 2
N=524
Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Acute Uncomplicated Plasmodium Falciparum Malaria
Bottom Line
View on ClinicalTrials.gov: NCT03167242 ↗Enrolled (actual)
524
Serious AEs
4.0%
Results posted
Feb 2022
Primary outcome: Primary: Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 — 46; 45; 47; 47 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- KAF156 (Drug); Coartem (Drug); Lumefantrine Solid Dispersion Formulation (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jun 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 |
46; 45; 47; 47; 44; 42 | — |
| PRIMARY PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156 |
5.35 | — |
| SECONDARY Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR) |
49; 47; 51; 53; 50; 51 | — |
| SECONDARY Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) |
48; 46; 48; 47; 44; 43 | — |
| SECONDARY Part A and Part B: Number of Participants With Recrudescence Events |
4; 3; 1; 1; 0; 2 | — |
| SECONDARY Part A and Part B: Number of Participants With Reinfection Events |
3; 7; 4; 7; 8; 2 | — |
| SECONDARY Part A and Part B: Fever Clearance Time (FCT) |
18.7; 22.5; 20.3; 16.6; 17.5; 19.2 | — |
| SECONDARY PK Run-in, Part A and Part B: Parasite Clearance Time (PCT) |
49.9; 48.4; 46.6; 39.9; 51.4; 49.7 | — |
| SECONDARY PK Run-in, Part A and Part B: Number of Participants With Parasitaemia |
12; 46; 46; 44; 52; 49 | — |
| SECONDARY Part A and Part B: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Last Treatment Dose (AUC0-24h) of KAF156 |
9.84; 21.7; 9.95; 5.91; 11; 10.9 | — |
| SECONDARY Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156 |
653; 1470; 1060; 665; 1470; 1320 | — |
| SECONDARY PK Run-in and Part A: Elimination Half-life (T½) of KAF156 |
25.0; 25.4; 29.9; 31.0; 35.8; 28.4 | — |
| SECONDARY PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156 |
4.23; 39.8; 5.99 | — |
Summary
This study was designed to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated Plasmodium falciparum malaria.
There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.
Eligibility Criteria
Inclusion Criteria
- Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and 2 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
- AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN
- Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
Data sourced from ClinicalTrials.gov (NCT03167242). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.