Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria
- Conditions
- Uncomplicated Plasmodium Falciparum Malaria
- Interventions
- Registration Number
- NCT07235020
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This is Cohort A1 of the Platform study (NCT05750628) to evaluate the efficacy and safety of INE963 in participants with uncomplicated Plasmodium falciparum malaria.
- Detailed Description
The Cohort A1 of this Platfom study (NCT05750628) is an open-label, randomized, multi-arm monotherapy part evaluating a single oral administration of an anti-malarial agent (INE963) at 3 parallel dose levels followed by optional adaptive sequential dose level(s).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- Male and female patients ≥18 years of age at screening.
- Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 5,000 to 150,000 asexual parasite count/μl of blood for P. falciparum
- Patients must weigh between 40 kg and 90 kg.
- Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
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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
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Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level < 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening
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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
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Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening.
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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.
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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/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A1: INE963 Dose Level 1 INE963 Cohort A1: INE963 Dose Level 1 Cohort A1: INE963 Dose Level 2 INE963 Cohort A1: INE963 Dose Level 2 Cohort A1: INE963 Dose Level 3 INE963 Cohort A1: INE963 Dose Level 3 Cohort A1: INE963 Dose Level 4 INE963 Cohort A1: INE963 Dose Level 4
- Primary Outcome Measures
Name Time Method Parasite clearance time (PCT) up to Day 7 To assess the parasite clearance time (PCT) of oral doses of an anti-malarial agent administered as monotherapy in participants 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.
- Secondary Outcome Measures
Name Time Method PCR-corrected and uncorrected ACPR Day 29 To assess the 28-day cure rate of an anti malarial agent administered orally as monotherapy 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 22 To characterize the pharmacokinetics (PK) of the anti-malarial agent administered orally as monotherapy.
Area under the concentration-time curve from time zero to infinity (AUCinf) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Elimination half-life (T1/2) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Apparent volume of distribution (V/F) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Maximum observed concentration (Cmax) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Time to reach maximum observed concentration (Tmax) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Total body clearance (CL/F) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Area under the concentration-time curve (AUC0-t) Day 22 To characterize PK of the anti-malarial agent administered orally as monotherapy.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇬Kampala, Uganda
Novartis Investigative Site🇺🇬Kampala, Uganda