Uncomplicated Plasmodium Falciparum Malaria
Conditions
Keywords
single dose cure malaria, uncomplicated malaria, Plasmodium falciparum, platform study, PLATINUM
Brief summary
This is Cohort B1 of the Platform study (NCT05750628) to evaluate the efficacy and safety of INE963 + Cipargamin in participants with uncomplicated Plasmodium falciparum malaria.
Detailed description
The Cohort B1 of this Platfom study (NCT05750628) is the open-label, randomized, two-arm combination therapy evaluating a dose of up to two anti-malarial agents as a loose combination vs. standard of care (SoC), Coartem in adult and adolescent participants.
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study was open-label, but Core Clinical Team is blinded to treatment information.
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients ≥12 years of age at screening. 2. Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 1,000 to 150,000 asexual parasite count/μl of blood for P. falciparum. 3. Patients must weigh between 35 kg and 90 kg at screening. 4. Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
Exclusion criteria
1. Patients with signs and symptoms of severe/complicated malaria at screening or mixed Plasmodium infection (i.e., infection with more than one malaria species) at screening 2. Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level \< 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening 3. Known clinically significant liver disease (e.g., chronic hepatitis, liver cirrhosis (compensated or decompensated), history of hepatitis B or C, hepatitis A or B vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis. Clinical or laboratory evidence of any of the following at screening: * 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 4. Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening. 5. Pregnant or nursing (lactating) women, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of effective contraception, and sexually active patients not willing to practice effective contraception. 6. History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as: * Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker * History of familial long QT syndrome or known family history of Torsades de Pointe. * Resting heart rate (physical exam or 12 lead ECG) \< 50 bpm Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) | Day 29 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parasite clearance time (PCT) | up to Day 7 | To assess the parasite clearance time (PCT) of oral anti malarial agent versus the standard of care (SoC) in participants with uncomplicated P. falciparum malaria |
| PCR-uncorrected ACPR | Day 29 | To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the SoC in participants with uncomplicated P. falciparum malaria. |
| Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Maximum observed concentration (Cmax) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Time to reach maximum observed concentration (Tmax) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Elimination half-life (T1/2) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Total body clearance (CL/F) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Apparent volume of distribution (V/F) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Area under the concentration-time curve from time zero to infinity (AUCinf) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
| Area under the concentration-time curve (AUC0-t) | Day 8 | To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as combination therapy. |
Countries
Burkina Faso, Côte d’Ivoire, Gabon, Ghana, Kenya, Rwanda, Uganda
Outcome results
None listed