Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Patients With Uncomplicated Plasmodium Falciparum Malaria

Официальное название

A Multi-part, Multi-center PLATform Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Anti-malarial Agents Administered as Monotherapy and/or Combination Therapy IN Patients With Uncomplicated Plasmodium Falciparum Malaria

Обзор

Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria

Подробное описание

The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adults, adolescents, and children with uncomplicated Plasmodium falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated for dose selection for future studies.

Вмешательства

• Препарат INE963
  oral INE963
• Препарат KAE609 (Cipargamin)
  oral KAE609 (Cipargamin)
• Препарат SoC (Coartem)
  SoC (Coartem)
• Препарат KLU156
  oral sachet KLU156 (KAF156 + lumefantrine)

Первичные конечные точки

• Part A: parasite clearance time (PCT) [Срок оценки: up to Day 7]
• Part B and C: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) [Срок оценки: Day 29]

Вторичные конечные точки (11)

• Part A: PCR-corrected and uncorrected ACPR [Срок оценки: Day 29]
• Parts B and C: PCT [Срок оценки: up to Day 7]
• Parts B and C: PCR-uncorrected ACPR [Срок оценки: Day 29]
• Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents (wherever possible) [Срок оценки: Day 22]
• Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents (wherever possible) [Срок оценки: Day 22]
• Maximum observed concentration (Cmax) of the anti-malarial agents [Срок оценки: Day 22]
• Time to reach maximum observed concentration (Tmax) [Срок оценки: Day 22]
• Elimination half-life (T1/2) of the anti-malarial agents (wherever possible) [Срок оценки: Day 22]
• Total body clearance (CL/F) of the anti-malarial agents (wherever possible) [Срок оценки: Day 22]
• Apparent volume of distribution (V/F) of the anti-malarial agents (wherever possible) [Срок оценки: Day 22]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Day 43]

Критерии участия

Критерии включения

• Male and female patients ≥18 years of age for Part A, ≥12 years of age for Part B and 2 to <12 years of age for Part C 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 for Part A and between 1,000 to 150,000 asexual parasite count/μl of blood for Parts B and C.
• Patients in Part A must weigh between 40 kg and 90 kg. Patients in Part B must weigh between 35 kg and 90 kg at screening. Patients in Part C must weigh at least 10 kg at screening.
• Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.

Критерии исключения

• 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
• Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level < 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening
• 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
• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Burkina Faso · 2 центра

• Novartis Investigative Site — Banfora
• Novartis Investigative Site — Nanoro

Côte d’Ivoire · 2 центра

• Novartis Investigative Site — Abidjan
• Novartis Investigative Site — Azaguié

Gabon · 2 центра

• Novartis Investigative Site — Lambaréné
• Novartis Investigative Site — Libreville

Ghana · 2 центра

• Novartis Investigative Site — Kintampo
• Novartis Investigative Site — Navrango

Kenya · 2 центра

• Novartis Investigative Site — Ahero
• Novartis Investigative Site — Kisumu

Uganda · 2 центра

• Novartis Investigative Site — Kampala
• Novartis Investigative Site — Tororo

Идентификаторы

NCT: NCT05750628 · CADPT13A12201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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