Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria
The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adults, adolescents, and children with uncomplicated Plasmodium falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated for dose selection for future studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
327
Novartis Investigative Site
Banfora, Burkina Faso
RECRUITINGNovartis Investigative Site
Nanoro, Burkina Faso
RECRUITINGPart A: parasite clearance time (PCT)
Part A: To assess the parasite clearance time (PCT) of oral doses of an anti-malarial agent administered as monotherapy in patients with uncomplicated P. falciparum malaria. PCT is defined as the time from the first positive blood slide at inclusion to the time of the first negative slide followed by two consecutive slides.
Time frame: up to Day 7
Part B and C: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR)
Part B and C: To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria. ACPR is defined as the absence of parasitemia on Study Day 29 irrespective of axillary temperature, without previously meeting any of the criteria of Early Treatment Failure (ETF) or Late Clinical Failure (LCF) or Late Parasitological Failure (LPF).
Time frame: Day 29
Part A: PCR-corrected and uncorrected ACPR
Part A: To assess the 28-day cure rate of an anti malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria
Time frame: Day 29
Parts B and C: PCT
Part B and C: To assess the parasite clearance time (PCT) of oral combinations of anti malarial agents versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria
Time frame: up to Day 7
Parts B and C: PCR-uncorrected ACPR
Part B and C: To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the SoC in patients with uncomplicated P. falciparum malaria
Time frame: Day 29
Novartis Pharmaceuticals
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
oral sachet KLU156 (KAF156 + lumefantrine)
Novartis Investigative Site
Abidjan, Côte d’Ivoire
RECRUITINGNovartis Investigative Site
Azaguié, Côte d’Ivoire
RECRUITINGNovartis Investigative Site
Lambaréné, Gabon
RECRUITINGNovartis Investigative Site
Libreville, Gabon
RECRUITINGNovartis Investigative Site
Kintampo, Ghana
RECRUITINGNovartis Investigative Site
Navrango, Ghana
RECRUITINGNovartis Investigative Site
Ahero, Kisumu County, Kenya
RECRUITINGNovartis Investigative Site
Kisumu, Kenya
RECRUITING...and 2 more locations
Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents (wherever possible)
To characterize the pharmacokinetics (PK) of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sample time (tlast)
Time frame: Day 22
Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents (wherever possible)
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. AUCinf is the AUC from time zero to infinity.
Time frame: Day 22
Maximum observed concentration (Cmax) of the anti-malarial agents
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. Cmax is the maximum (peak) observed plasma, blood, serum, or other blood fluid drug concentration after single dose administration.
Time frame: Day 22
Time to reach maximum observed concentration (Tmax)
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.
Time frame: Day 22
Elimination half-life (T1/2) of the anti-malarial agents (wherever possible)
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. T1/2 is the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve.
Time frame: Day 22
Total body clearance (CL/F) of the anti-malarial agents (wherever possible)
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. Cl/F is the total body clearance of drug from the plasma.
Time frame: Day 22
Apparent volume of distribution (V/F) of the anti-malarial agents (wherever possible)
To characterize PK of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] in patients with uncomplicated P. falciparum malaria. V/F is the apparent volume of distribution during terminal phase.
Time frame: Day 22
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Day 43