Clinical trial NCT05750628: Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Patients With Uncomplicated Plasmodium Falciparum Malaria
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Uncomplicated Plasmodium Falciparum Malaria
Keywords: malaria
uncomplicated malaria
Plasmodium falciparum
platform study
PLATINUM
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 327
Sex: ALL
Minimum age (years): 2
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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.
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/exclusion criteria may apply.

Primary outcomes:
measure: Part A: parasite clearance time (PCT)
timeFrame: up to Day 7
measure: Part B and C: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR)
timeFrame: Day 29
Secondary outcomes:
measure: Part A: PCR-corrected and uncorrected ACPR
timeFrame: Day 29
measure: Parts B and C: PCT
timeFrame: up to Day 7
measure: Parts B and C: PCR-uncorrected ACPR
timeFrame: Day 29
measure: Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents (wherever possible)
timeFrame: Day 22
measure: Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents (wherever possible)
timeFrame: Day 22
measure: Maximum observed concentration (Cmax) of the anti-malarial agents
timeFrame: Day 22
measure: Time to reach maximum observed concentration (Tmax)
timeFrame: Day 22
measure: Elimination half-life (T1/2) of the anti-malarial agents (wherever possible)
timeFrame: Day 22
measure: Total body clearance (CL/F) of the anti-malarial agents (wherever possible)
timeFrame: Day 22
measure: Apparent volume of distribution (V/F) of the anti-malarial agents (wherever possible)
timeFrame: Day 22
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 43
Other outcomes:
Locations:
city: Banfora
country: Burkina Faso
facility: Novartis Investigative Site
city: Nanoro
country: Burkina Faso
facility: Novartis Investigative Site
city: Abidjan
country: Côte D'Ivoire
facility: Novartis Investigative Site
city: Azaguie
country: Côte D'Ivoire
facility: Novartis Investigative Site
city: Lambarene
country: Gabon
facility: Novartis Investigative Site
city: Libreville
country: Gabon
facility: Novartis Investigative Site
city: Kintampo
country: Ghana
facility: Novartis Investigative Site
city: Navrango
country: Ghana
facility: Novartis Investigative Site
city: Ahero
country: Kenya
facility: Novartis Investigative Site
state: Kisumu
city: Kisumu
country: Kenya
facility: Novartis Investigative Site
city: Kampala
country: Uganda
facility: Novartis Investigative Site
city: Tororo
country: Uganda
facility: Novartis Investigative Site
Study officials:
References: