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

NCT05750628 | Recruiting Phase 2 DMC

• 1 other identifier: CADPT13A12201
• Study Type: interventional
• Target: 327
• Locations: 6 countries
• Sites: 12

Brief Summary

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

Conditions

Uncomplicated Plasmodium Falciparum Malaria

Keywords

malaria; uncomplicated malaria; Plasmodium falciparum; platform study; PLATINUM

Outcome Measures

Primary Outcomes (2)

• 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 and C: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR)

  Part B and C: 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 Outcomes (11)

• Part A: PCR-corrected and uncorrected ACPR

  Day 29

• Parts B and C: PCT

  up to Day 7

• Parts B and C: PCR-uncorrected ACPR

  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)

  Day 22

• Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents (wherever possible)

  Day 22

Study Arms (10)

Cohort A1: Dose Level 1 INE963

EXPERIMENTAL

Cohort A1: Dose Level 1 INE963

Drug: INE963

Cohort A1: Dose Level 2 INE963

EXPERIMENTAL

Cohort A1: Dose Level 2 INE963

Drug: INE963

Cohort A1: Dose Level 3 INE963

EXPERIMENTAL

Cohort A1: Dose Level 3 INE963

Drug: INE963

Cohort B1: Cipargamin + INE963

EXPERIMENTAL

Cohort B1: Cipargamin + INE963

Drug: KAE609 (Cipargamin)

Cohort B1: SoC (Coartem)

ACTIVE COMPARATOR

Cohort B1: SoC (Coartem)

Drug: SoC (Coartem)

Cohort B2: Cipargamin + KLU156

EXPERIMENTAL

Cohort B2: Cipargamin + KLU156

Drug: KAE609 (Cipargamin); Drug: KLU156

Cohort B2: SoC (Coartem)

ACTIVE COMPARATOR

Cohort B2: SoC (Coartem)

Drug: SoC (Coartem)

Cohort C2: Cipargamin + KLU156

EXPERIMENTAL

Cohort C2: Cipargamin + KLU156

Drug: KAE609 (Cipargamin); Drug: KLU156

Cohort C2: SoC (Coartem)

ACTIVE COMPARATOR

Cohort C2: SoC (Coartem)

Drug: SoC (Coartem)

Cohort A1: Dose Level 4 INE963

EXPERIMENTAL

Cohort A1: Dose level 4 INE963

Drug: INE963

Interventions

INE963 DRUG

oral INE963

Cohort A1: Dose Level 1 INE963; Cohort A1: Dose Level 2 INE963; Cohort A1: Dose Level 3 INE963; Cohort A1: Dose Level 4 INE963

KAE609 (Cipargamin) DRUG

oral KAE609 (Cipargamin)

Cohort B1: Cipargamin + INE963; Cohort B2: Cipargamin + KLU156; Cohort C2: Cipargamin + KLU156

SoC (Coartem) DRUG

SoC (Coartem)

Cohort B1: SoC (Coartem); Cohort B2: SoC (Coartem); Cohort C2: SoC (Coartem)

KLU156 DRUG

oral sachet KLU156 (KAF156 + lumefantrine)

Cohort B2: Cipargamin + KLU156; Cohort C2: Cipargamin + KLU156

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Banfora, Burkina Faso

RECRUITING

Novartis Investigative Site

Nanoro, BP 18, Burkina Faso

RECRUITING

Novartis Investigative Site

Abidjan, 13BP972, Côte d’Ivoire

RECRUITING

Novartis Investigative Site

Azaguié, BP 173, Côte d’Ivoire

RECRUITING

Novartis Investigative Site

Lambaréné, BP 242, Gabon

RECRUITING

Novartis Investigative Site

Libreville, BP 1437, Gabon

RECRUITING

Novartis Investigative Site

Kintampo, 92037, Ghana

RECRUITING

Novartis Investigative Site

Navrango, VWJ6+8WF, Ghana

RECRUITING

Novartis Investigative Site

Ahero, Kisumu County, 40100, Kenya

RECRUITING

Novartis Investigative Site

Kisumu, 40100, Kenya

RECRUITING

Novartis Investigative Site

Kampala, Uganda

RECRUITING

Novartis Investigative Site

Tororo, 10102, Uganda

RECRUITING

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

INE963; NITD 609; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This study is open-label, but certain members of the CTT will be blinded to the treatment information
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: March 2, 2023
• Study Start: January 23, 2024
• Primary Completion (Estimated): June 9, 2026
• Study Completion (Estimated): June 23, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

GA (2); GH (2); BU (2); KE (2); CÔ (2); UG (2)