Health Trials

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

ConditionUncomplicated Plasmodium Falciparum Malaria
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2-100
SponsorNovartis Pharmaceuticals

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • INE963

    Drug

    oral INE963

  • KAE609 (Cipargamin)

    Drug

    oral KAE609 (Cipargamin)

  • SoC (Coartem)

    Drug

    SoC (Coartem)

  • KLU156

    Drug

    oral sachet KLU156 (KAF156 + lumefantrine)

Treatment groups

327 Participants
are divided into 10 treatment groups

10

Treatment groups

See each treatment group below.

Group A: Cohort A1: Dose Level 1 INE963Experimental treatment 1 intervention
Group B: Cohort A1: Dose Level 2 INE963Experimental treatment 1 intervention
Group C: Cohort A1: Dose Level 3 INE963Experimental treatment 1 intervention
Group D: Cohort B1: Cipargamin + INE963Experimental treatment 1 intervention
Group E: Cohort B1: SoC (Coartem)Active comparator 1 intervention
Group F: Cohort B2: Cipargamin + KLU156Experimental treatment 2 interventions
Group G: Cohort B2: SoC (Coartem)Active comparator 1 intervention
Group H: Cohort C2: Cipargamin + KLU156Experimental treatment 2 interventions
Group I: Cohort C2: SoC (Coartem)Active comparator 1 intervention
Group J: Cohort A1: Dose Level 4 INE963Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
up to Day 7
2

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).

Time frame
Day 29

Secondary outcomes

1

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

Time frame
Day 29
2

Parts B and C: PCT

Part B and C: 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

Time frame
up to Day 7
3

Parts B and C: PCR-uncorrected ACPR

Part B and C: 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

Time frame
Day 29
4

Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents (wherever possible)

To characterize the pharmacokinetics (PK) of each anti-malarial agent administered orally as monotherapy \[Part A\] and/or as combination therapy \[Parts B and C\] 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)

Time frame
Day 22

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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