Efficacy, Safety and Tolerability of KAF156 in Combination With Lumefantrine Solid Dispersion Formulation (LUM-SDF) in Pediatric Population With Uncomplicated Plasmodium Falciparum Malaria
KALUMI
A Phase 2 Interventional, Multicenter, Randomized, Open-label Study in Three Age-descending Cohorts to Evaluate Efficacy, Safety and Tolerability of KAF156 and Lumefantrine-SDF Combination in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in a Pediatric Population
2 other identifiers
interventional
295
5 countries
9
Brief Summary
This study aims to determine the efficacy, safety and tolerability of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in pediatric patients (6 months to \< 18 years of age) with uncomplicated P. falciparum malaria. There is an unmet medical need for anti-malarial treatment with a new mechanism of action to reduce the probability of developing resistance.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2021
Typical duration for phase_2
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2020
CompletedFirst Posted
Study publicly available on registry
September 14, 2020
CompletedStudy Start
First participant enrolled
February 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 13, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 28, 2024
CompletedSeptember 25, 2024
September 1, 2024
3.5 years
September 5, 2020
September 24, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
PCR-corrected adequate clinical and parasitological response (ACPR) at Day 29 (i.e., 28 days post-dose) (Cohorts 1 and 2 pooled).
The primary efficacy variable is the PCR corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 (Cohorts 1 and 2 pooled). In case that Cohort 2 stops early, such as after the first 24 patients, the study objectives will be assessed based on Cohort 1 data alone. A patient is considered as PCR corrected ACPR at Day 29 if the patient does not meet any of the criteria of early treatment failure (ETF) (up to Day 4), late clinical failure (LCF) (Day 5 to Day 29) or late parasitological failure (LPF) (Day 8 to Day 29), and is absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days (Day 8 or later) is due to reinfection based on PCR genotyping. A presence of parasitaemia after 7 days of treatment initiation is considered as a reinfection only if the parasitaemia is clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later match with the parasite strain at baseline based on PCR genotyping.
Day 29
Secondary Outcomes (15)
Percentage of Participants with Polymerase Chain Reaction (PCR)-corrected and uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15 and 43
Day 15, Day 43
Percentage of Participants with Polymerase Chain Reaction (PCR)-corrected and uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 (Run-in Cohort)
Day 29
Time to parasite clearance (PCT)
up to 43 days
Time to fever clearance (FCT)
up to 43 days
Proportion of patients with Early Treatment Failure (ETF)
Day 1 to Day 4
- +10 more secondary outcomes
Study Arms (4)
Run-in - KAF156 and LUM-SDF QD for 2 days in fasted condition
EXPERIMENTALKAF156 and LUM-SDF QD (once daily) for 2 days in fasted condition
Run-in - KAF156 and LUM-SDF QD for 2 days in fed condition
EXPERIMENTALKAF156 and LUM-SDF QD (once daily) for 2 days in fed condition
Cohort 1/2 - KAF156 and LUM-SDF QD (once daily) in either a 2-day or 3-day dose regimen
EXPERIMENTALKAF156 and LUM-SDF QD (once daily) in either a 2-day or 3-day dose regimen. Food recommendation will be issued after the Run-in Cohort based on efficacy, safety, tolerability and PK data).
Cohort 1/2 - Coartem® BID (twice a day) for 3 days
ACTIVE COMPARATORCoartem® BID (twice a day) for 3 days (will be administered with food and doses will be based on patient's body weight as per product label).
Interventions
Provided as 50 mg or 100 mg tablets, to be taken QD 2 or 3 Days in combination with LUM-SDF, dose is based on body weight
Provided as 60 mg, 120 mg or 240 mg powder in sachet, to be taken QD 2 or 3 Days in combination with KAF156, dose is based on body weight
Coartem® (dispersible tablets in blister pack) (for Cohorts 1 and 2), dose is based on body weight
Eligibility Criteria
You may qualify if:
- In run-in cohort: Male and female patients 12 to \< 18 years of age, with a body weight
- kg In Cohort 1: Male and female patients 2 to \< 12 years of age, with a body weight ≥ 10.0 kg In Cohort 2: Male and female patients 6 months to \< 2 years of age, with a body weight
- Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films
- P. falciparum parasitemia of ≥ 1,000 and ≤ 150,000 parasites/μL at the time of prescreening for the Run-in Cohort; and P. falciparum parasitemia of ≥ 1,500 and ≤ 150,000 parasites/μL at the time of pre-screening for Cohorts 1 and 2
- Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.0 ºC; or history of fever during the previous 24 hours (at least documented verbally)
- Written informed consent has been obtained from parent / legal guardian before any assessment is performed. If the parent/legal guardian is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines
- The patient and his/her parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned
You may not qualify if:
- Mixed Plasmodium infections as per light microscopy results
- Signs and symptoms of severe malaria according to WHO 2015 (see Section 16.4)
- Significant, non-plasmodial co-infections including tuberculosis
- Patients with concurrent febrile illnesses (e.g., typhoid fever, known or suspected COVID19)
- Known relevant liver disease e.g. chronic hepatitis, cirrhosis, compensated or decompensated, history of hepatitis B or C, hepatitis B or A vaccination in last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis
- Major congenital defects
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection or family history of congenital or hereditary immunodeficiency
- Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior to recruitment. (For corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed)
- Active duodenal ulcer, ulcerative colitis, Crohn's disease, chronic (i.e., \> 2 weeks) use of non-steroidal anti-inflammatory drugs (NSAIDs)
- Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
- Anemia (hemoglobin level \<7 g/dL)
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., HIV patients on ART therapy or TB patients on treatment), or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory evidence of any of the following:
- AST/ALT \> 3 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
- Resting QT interval corrected by Fridericia's formula (QTcF) \> 450 ms at screening
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Novartis Investigative Site
Banfora, Burkina Faso
Novartis Investigative Site
Bobo-Dioulasso, 01, Burkina Faso
Novartis Investigative Site
Ouagadougou, Burkina Faso
Novartis Investigative Site
Sabou, 06 BP 10248, Burkina Faso
Novartis Investigative Site
Abidjan, 13BP972, Côte d’Ivoire
Novartis Investigative Site
Commune de La Kenya Lubumbashi, Du Haut Katanga, Democratic Republic of the Congo
Novartis Investigative Site
Lambaréné, BP 242, Gabon
Novartis Investigative Site
Kati, Mali
Novartis Investigative Site
Sotouba, Mali
Related Publications (1)
Ogutu B, Yeka A, Kusemererwa S, Thompson R, Tinto H, Toure AO, Uthaisin C, Verma A, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, N'Guessan TL, Nassa GJW, Nyantaro M, Tina LO, Singh PK, El Gaaloul M, Marrast AC, Chikoto H, Csermak K, Demin I, Mehta D, Pathan R, Risterucci C, Su G, Winnips C, Kaguthi G, Fofana B, Grobusch MP. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial. Lancet Infect Dis. 2023 Sep;23(9):1051-1061. doi: 10.1016/S1473-3099(23)00209-8. Epub 2023 Jun 13.
PMID: 37327809DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Treatment and food condition during the Run-in cohort will be open to patients/patients' parents/legal guardian, investigators staff and study monitors, as well as to the Clinical Trial Team (CTT) to allow continuous review of safety, drug exposure and efficacy data in pediatric population. For Cohorts 1 and 2, treatment/food condition will be open to patients/patients' parents/legal guardian, investigators staff and study monitors but will be blinded to the Clinical Trial Team (CTT).
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 5, 2020
First Posted
September 14, 2020
Study Start
February 16, 2021
Primary Completion
August 13, 2024
Study Completion
August 28, 2024
Last Updated
September 25, 2024
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will share
Novartis is commited to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.