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

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

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

Study Overview

• Status: Recruiting
• Conditions: Uncomplicated Plasmodium Falciparum Malaria
• Intervention / Treatment: Drug: INE963; Drug: SoC (Coartem); Drug: KLU156; Drug: KAE609 (Cipargamin)

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 207
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Côte D'Ivoire
  • Azaguie, Côte D'Ivoire, BP 173
    • Recruiting
    • Novartis Investigative Site
• Ghana
  • Navrango, Ghana, VWJ6+8WF
    • Recruiting
    • Novartis Investigative Site
• Kenya
  • Central Kenya
    • Kisumu, Central Kenya, Kenya, 3433-40100
      • Recruiting
      • Novartis Investigative Site
  • Kisumu
    • Ahero, Kisumu, Kenya, 40100
      • Recruiting
      • Novartis Investigative Site
• Uganda
  • Kampala, Uganda
    • Recruiting
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: Dose Level 1 INE963	Drug: INE963; oral INE963
Experimental: Cohort A1: Dose Level 2 INE963	Drug: INE963; oral INE963
Experimental: Cohort A1: Dose Level 3 INE963	Drug: INE963; oral INE963
Experimental: Cohort B1: KAE609 + INE963	Drug: INE963; oral INE963; Drug: KAE609 (Cipargamin); oral KAE609 (Cipargamin)
Active Comparator: Cohort B1: SoC (Coartem)	Drug: SoC (Coartem); SoC (Coartem)
Experimental: Cohort B2: KAE609 + KLU156	Drug: KLU156; oral sachet KLU156 (KAF156 + lumefantrine); Drug: KAE609 (Cipargamin); oral KAE609 (Cipargamin)
Active Comparator: Cohort B2: SoC (Coartem)	Drug: SoC (Coartem); SoC (Coartem)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; malaria; platform study; uncomplicated malaria; PLATINUM
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: CADPT13A12201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No