Efficacy, safety and tolerability of KLU156 in adults and children = 5 kg body weight with uncomplicated P. falciparum malaria
- Conditions
- Malaria
- Registration Number
- PACTR202303470809477
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 1500
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.
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) < 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 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 < 7 g/dL)
7. 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.
8. Any of the following:
•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
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).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Core Phase:<br>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.<br>
- Secondary Outcome Measures
Name Time Method