Efficacy, Safety and Tolerability of KLU156 in Adults and Children With Uncomplicated P. Falciparum Malaria

NCT05842954
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Phase
Phase 3
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Recruitment status
Completed
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Participants
1,720
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Lead sponsor
Novartis Pharmaceuticals
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Start date
2024-03-07
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Number of sites
33
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Summary
This study aims to confirm the efficacy, safety and tolerability of KLU156, a fixed dose combination of ganaplacide (KAF156) and a solid dispersion formulation of lumefantrine (lumefantrine-SDF), when administered once daily for three days in adults and children ≥ 10 kg of body weight suffering from uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection). In the Extension phase, the safety, tolerability and efficacy of repeated treatment with KLU156 will be assessed for a maximum of two years in patients who did not experience early treatment failure (ETF), who did not experience any study treatment-related SAE (Serious Adverse Event) previously and who gave informed consent to participate in the Extension phase.
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Acronym
KALUMA
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Short title
Efficacy, Safety and Tolerability of KLU156 in Adults and Children With Uncomplicated P. Falciparum Malaria
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Official title
A Randomized, Open-label, Multicenter Study to Compare Efficacy, Safety and Tolerability of KLU156 With Coartem® in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Adults and Children Followed by an Extension Phase With Repeated KLU156 Treatment
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2025-11-25
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First posted
2023-05-06
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Registry last updated
2026-01-27
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Primary completion date
2025-06-27
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Start date
2024-03-07
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Actual participants
1,720
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Participants
1,720
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
33
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Novartis Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05842954
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ClinicalTrials.gov ID
NCT05842954
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Single masking
Masking description
The Novartis clinical trial team (CTT) will be blinded to the identity of the treatment from the time of randomization until the database lock for the analysis of the Core phase. Prior to unblinding the data of the Core phase (for the Novartis CTT), at least three DMC reviews are planned to minimize risks in this vulnerable patient population: 1. Once the first 200 patients (across both treatment arms) in the Core phase have been dosed and followed up to at least Day 22. 2. Once the first 750 patients (across both treatment arms) in the Core phase have been dosed and followed up to at least Day 22. 3. Additional DMC reviews may be conducted ad-hoc during the study, as deemed necessary. All safety data from the Core phase as well as from the Extension phase that are available at these 2 scheduled timepoints will be included in the DMC reviews. After the database lock of the Core phase, the CTT will be unblinded.
Masked roles
Outcome assessors
Sources for study design
clinicaltrials.gov

  1. PCR-corrected adequate clinical and parasitological response (ACPR)

    Timeframe: Day 29 (i.e., 28 days post-first dose administration)

    To confirm the efficacy of KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem (non-inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29. This primary outcome is applicable to non-US submission.

  2. Uncorrected ACPR (US NDA submission)

    Timeframe: Day 29

    To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29. This primary outcome is applicable to US New Drug Application (NDA) submission.

  1. Uncorrected ACPR

    Timeframe: Day 29

    To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29

  2. PCR-corrected and uncorrected ACPR

    Timeframe: Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)

    To confirm the efficacy of KLU156 by assessing uncorrected and PCR-corrected ACPR at additional time points

  3. Incidence rate of recrudescence and new infection

    Timeframe: Days 22, 29 and 43

    Proportion of patients with recrudescence and new infections between the two treatment arms

  4. Fever Clearance Time

    Timeframe: Up to Day 3

    To confirm the efficacy of KLU156 by assessing fever clearance between the two treatment arms

  5. Parasite Clearance Time

    Timeframe: Up to Day 3

    To assess parasite clearance time between the two treatment arms

  6. Gametocyte Clearance Time

    Timeframe: Up to Day 3

    To confirm the efficacy of KLU156 by assessing gametocyte clearance between the two treatment arms

  7. Proportion of patients with parasitemia

    Timeframe: 12, 24, 48 and 72 hours after treatment

    For the parasitemia assessment, blood sampling can be done by means of a finger prick except when the timing for parasitology assessments coincides with time for clinical laboratory tests, in which case, blood sample can be taken from the venous blood collected for clinical laboratory analyses.

  8. Gametocytemia

    Timeframe: From baseline up to Day 43

    Disappearance or development of gametocytemia in patients with or without gametocytemia at baseline (pre-first dose administration), respectively

  9. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: Day 43

    Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs.

  10. Extension phase: PCR-corrected and uncorrected ACPR

    Timeframe: Day 29 of malaria episode

    To evaluate efficacy over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years

  11. Extension phase: KLU156-related AE/SAE incidence and severity by malaria episode

    Timeframe: Up to 2 years

    To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years

  12. Extension phase: Gametocyte carriage over time

    Timeframe: Up to 2 years

    To assess gametocyte carriage over time by malaria episode in the extension phase

Sources for outcomes
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Sex
All
Age groups
Children, Adults, Older adults
Minimum age
2 Months
Maximum age
100 Years
Healthy volunteers
No

Key Inclusion criteria (Core phase)

  1. Male or female patients ≥ 10 kg of body weight.
  2. Microscopically confirmed diagnosis of uncomplicated P. falciparum malaria with an asexual P. falciparum parasitemia ≥ 1,000 and ≤ 200,000 parasites/µL at the time of pre-screening with or without other Plasmodium spp. co-infection.
  3. Axillary temperature ≥ 37.5 ºC or oral temperature ≥ 38.0 ºC or tympanic/rectal temperature ≥ 38.5 ºC; or history of fever during the previous 24 hours (at least documented verbally)
  4. Negative pregnancy test for patients of childbearing potential
  5. Signed informed consent must be obtained before any assessment is performed; for minors, signed informed consent must be obtained from parent/legal guardian. 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 it along with parent/legal guardian consent or as per local ethical standards
  6. The patient and/or their 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.

Key Exclusion criteria (Core phase)

  1. Signs and symptoms of severe malaria according to WHO 2015 (World Health Organization)

  2. Concurrent febrile illnesses (e.g., typhoid fever, known or suspected dengue fever, known COVID19)

  3. Severe malnutrition. For patients ≥ 12 years: body mass index (BMI) < 16.0. For children < 12 years: less than 70% of median normalized WHO reference weight or very low mid-upper arm circumference (MUAC < 115 mm)

  4. Repeated vomiting (defined as > 3 times in the 24 hours prior to start of screening) or severe diarrhea (defined as > 3 watery stools in the 24 hours prior to start of screening)

  5. Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia

  6. Anemia (hemoglobin level <7 g/dL)

  7. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., Human immunodeficiency virus (HIV) patients on antiretroviral therapy (ART) or tuberculosis (TB) patients on treatment), or which may jeopardize the patient in case of participation in the study.

  8. Any of the following:

    • Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) > 3 x the upper limit of normal (ULN), regardless of the level of total bilirubin
    • Total bilirubin > 3 x ULN
    • Resting QT interval corrected by Fridericia's formula (QTcF) > 450 ms at screening

  9. Prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five plasma half-lives (or within 4 weeks of screening if half-life is unknown)

  10. History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease

  11. Pregnant or nursing (lactating) patients.

Other protocol-defined inclusion/exclusion criteria may apply.

Sources for eligibility
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  • Novartis Investigative SiteBanfora, Burkina Faso
  • Novartis Investigative SiteBobo-Dioulasso, Burkina Faso
  • Novartis Investigative SiteNanoro, Burkina Faso
  • Novartis Investigative SiteOuagadougou, Burkina Faso
  • Novartis Investigative SiteSabou, Burkina Faso
  • Novartis Investigative SiteAbidjan, Côte d’Ivoire
  • Novartis Investigative SiteAgboville, Côte d’Ivoire
  • Novartis Investigative SiteAzaguié, Côte d’Ivoire
  • Novartis Investigative SiteKimpese, Democratic Republic of the Congo
  • Novartis Investigative SiteKisantu, Democratic Republic of the Congo
  • Novartis Investigative SiteLubumbashi, Democratic Republic of the Congo
  • Novartis Investigative SiteKenge, Democratic Republic of the Congo
  • Novartis Investigative SiteMasi-Manimba, Democratic Republic of the Congo
  • Novartis Investigative SiteLambaréné, Gabon
  • Novartis Investigative SiteLibreville, Gabon
  • Novartis Investigative SiteKintampo, Ghana
  • Novartis Investigative SiteNavrango, Ghana
  • Novartis Investigative SiteKombewa, Kenya
  • Novartis Investigative SiteNairobi, Kenya
  • Novartis Investigative SiteSiaya, Kenya
  • Novartis Investigative SiteSotouba, Mali
  • Novartis Investigative SiteNiamey, Niger
  • Novartis Investigative SiteGicumbi, Rwanda
  • Novartis Investigative SiteKigali, Rwanda
  • Novartis Investigative SiteKigali, Rwanda

And 8 more, listed on the interactive page.

Sources for sites
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Other registry identifiers

  • 2022-002675-10
Sources for references
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Related records

Drugs (1)

Collaborators (1)

Lead sponsors (1)

Conditions (2)