Evaluating anti-malarial agents for uncomplicated malaria

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

This study is testing different malaria medications to see how well they work and how safe they are for people with uncomplicated malaria.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 327 (estimated)
• Ages: 2 Years to 100 Years
• Sex: All
• Sponsor: Novartis (industry)
• Locations: 12 sites (Banfora and 11 other locations)
• Trial ID: NCT05750628 on ClinicalTrials.gov

What this trial studies

This platform study aims to assess the efficacy and safety of various anti-malarial agents in treating uncomplicated Plasmodium falciparum malaria. It involves administering these agents either as monotherapy or in combination with other treatments to patients of different age groups. The study will also evaluate the safety, tolerability, and pharmacokinetics of the drugs to inform future dosing strategies. Participants will be monitored for their parasiticidal response and overall health outcomes.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 2 years and older with confirmed uncomplicated Plasmodium falciparum malaria.

Not a fit: Patients with severe malaria symptoms or mixed infections will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective treatment options for patients suffering from uncomplicated malaria.

How similar studies have performed: Previous studies have shown promise in evaluating anti-malarial agents, but this platform approach is relatively novel.

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.

Where this trial is running

Banfora and 11 other locations

• Novartis Investigative Site — Banfora, Burkina Faso (RECRUITING)
• Novartis Investigative Site — Nanoro, Burkina Faso (RECRUITING)
• Novartis Investigative Site — Abidjan, Côte d’Ivoire (RECRUITING)
• Novartis Investigative Site — Azaguié, Côte d’Ivoire (RECRUITING)
• Novartis Investigative Site — Lambaréné, Gabon (RECRUITING)
• Novartis Investigative Site — Libreville, Gabon (RECRUITING)
• Novartis Investigative Site — Kintampo, Ghana (RECRUITING)
• Novartis Investigative Site — Navrango, Ghana (RECRUITING)
• Novartis Investigative Site — Ahero, Kisumu County, Kenya (RECRUITING)
• Novartis Investigative Site — Kisumu, Kenya (RECRUITING)
• Novartis Investigative Site — Kampala, Uganda (RECRUITING)
• Novartis Investigative Site — Tororo, Uganda (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Uncomplicated Plasmodium Falciparum Malaria, malaria, uncomplicated malaria, Plasmodium falciparum, platform study, PLATINUM