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

Uncomplicated Plasmodium Falciparum Malaria Clinical Trial

— PLATINUM  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05750628
• Other study ID #: CADPT13A12201
• Status: Recruiting
• Phase: Phase 2
• Start date: January 23, 2024
• Est. completion date: October 30, 2025

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 adult and adolescent patients 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 207
• Est. completion date: October 30, 2025
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. Male and female patients =18 years of age for Part A and =12 years of age for Part B 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 Part B

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.

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) < 60 bpm Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Uncomplicated Plasmodium Falciparum Malaria

Intervention

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

Locations

Country	Name	City	State
Côte D'Ivoire	Novartis Investigative Site	Azaguie
Ghana	Novartis Investigative Site	Navrango
Kenya	Novartis Investigative Site	Ahero	Kisumu
Kenya	Novartis Investigative Site	Kisumu	Central Kenya
Uganda	Novartis Investigative Site	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Côte D'Ivoire,  Ghana,  Kenya,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: parasite clearance time (PCT)	Part A: To assess the parasite clearance time (PCT) of oral doses of an anti-malarial agent administered as monotherapy in patients 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.	up to Day 7
Primary	Part B: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR)	Part B: To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria. 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).	Day 29
Secondary	Part A: PCR-corrected and uncorrected ACPR	Part A: To assess the 28-day cure rate of an anti malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria	Day 29
Secondary	Part B: PCT	Part B: To assess the parasite clearance time (PCT) of oral combinations of anti malarial agents versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria	up to Day 7
Secondary	Part B: PCR-uncorrected ACPR	Part B: To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the SoC in patients with uncomplicated P. falciparum malaria	Day 29
Secondary	Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents	To characterize the pharmacokinetics (PK) of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sample time (tlast)	Day 22
Secondary	Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. AUCinf is the AUC from time zero to infinity.	Day 22
Secondary	Maximum observed concentration (Cmax) of the anti-malarial agents	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. Cmax is the maximum (peak) observed plasma, blood, serum, or other blood fluid drug concentration after single dose administration.	Day 22
Secondary	Time to reach maximum observed concentration (Tmax)	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.	Day 22
Secondary	Elimination half-life (T1/2) of the anti-malarial agents	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. T1/2 is the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve.	Day 22
Secondary	Total body clearance (CL/F) of the anti-malarial agents	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. Cl/F is the total body clearance of drug from the plasma.	Day 22
Secondary	Apparent volume of distribution (Vz/F) of the anti-malarial agents	To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria. Vz/F is the apparent volume of distribution during terminal phase.	Day 22
Secondary	Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs.	Day 43