Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria (Cohort B2)
- Conditions
- Uncomplicated Plasmodium Falciparum Malaria
- Interventions
- Registration Number
- NCT07235033
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This is Cohort B2 of the Platform study (NCT05750628) to evaluate the efficacy and safety of Cipargamin + KLU156 in participants with uncomplicated Plasmodium falciparum malaria
- Detailed Description
The Cohort B2 of this Platfom study (NCT05750628) is the open-label, randomized, two-arm combination therapy evaluating a single oral dose of up to three anti-malarial agents as a loose combination vs. standard of care (SoC), Coartem in adult and adolescent participants.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Male and female patients ≥12 years of age at screening.
- 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.
- Patients must weigh between 35 kg and 90 kg at screening.
- Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
-
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.
-
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 B2: KLU156 + cipargamin Cipargamin Cohort B2: KLU156 + cipargamin Cohort B2: KLU156 + cipargamin KLU156 Cohort B2: KLU156 + cipargamin Cohort B2: SoC (Coartem) SoC (Coartem) Cohort B2: SoC (Coartem)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇬Tororo, Uganda
Novartis Investigative Site🇺🇬Tororo, Uganda