Malaria
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core Phase: 1. Male or female patients = 5 kg of body weight and = 2 months of age 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 h (at least documented verbally) 4. Negative pregnancy test for patients of childbearing potential 5. Signed informed consent (pre-screening and screening for the Core phase) must be obtained before any assessment is performed; for minors, signed informed consent must be obtained from parent/legal guardian (LAR). If the parent/LAR 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 parental/LAR consent or as per local ethical standards 6. The patient and/or their parent/LAR is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned. Extension Phase: 1. Patients randomized into the Core phase and having completed it. 2. Signed informed consent (for the Extension phase) must be obtained before any assessment is performed; for minors, signed informed consent must be obtained from parent/LAR. If the parent/LAR 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.
Exclusion criteria
Exclusion criteria: Core Phase: 1. Signs and symptoms of severe malaria according to WHO 2015 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) 3 times in the 24 h prior to start of screening) or severe diarrhea (defined as >3 watery stools in the 24 h 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 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 Extension Phase: Patients meeting the following criteria in the Core phase are not eligible for transition into the Extension phase: • Early Treatment Failure (KLU156 or Coartem treatment arm) • Patients with reported study treatment-related SAE (KLU156 or Coartem).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Core Phase: To confirm the efficacy of KLU156 in adults and children = 5 kg body weight and = 2 months of age 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Core Phase: 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. ;Core Phase: To confirm the efficacy of KLU156 by assessing uncorrected and PCR-corrected ACPR at additional time points, as well as fever and parasite clearance times, gametocyte carriage over time between the two treatment arms. ;Core Phase: To compare the safety and tolerability profile of the two treatment arms on adverse events (AEs), general laboratory, vital signs and ECG measurements. ;Extension Phase: To assess the safety and tolerability over repeated treatment with KLU156 in adults and children = 5 kg body weight and = 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years. ;Extension Phase: To evaluate efficacy over repeated treatment with KLU156 in adults and children = 5 kg body weight and = 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years. | — |
Countries
Burkina Faso, Congo, Cote Divoire, Democratic Republic of the Congo, Gabon, Ghana, Kenya, Malawi, Mali, Mozambique, Niger, Nigeria, Rwanda, Tanzania, Uganda, Zambia
Contacts
Public ContactNovartis Pharma AG Novartis Pharma AG
Trial Director
Outcome results
None listed