Clinical trial NCT04020653: A Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria
Official title: A Pilot, Double-blind, Randomized, Parallel-group, Placebo-controlled, Exploratory Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Malaria
Keywords: Uncomplicated malaria
sodium ferrous citrate (SFC)
5-aminolevulinic acid hydrochloride (5-ALA HCl)
artemisinin-based combination therapy
Lead sponsor: Neopharma Japan Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2019-07-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot, double-blind, randomized, parallel-group, placebo-control, exploratory study to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride (5-ALA HCl) and sodium ferrous citrate (SFC) added on artemisinin-based combination therapy (ACT) compared with ACT alone in the treatment of malaria. Patients who are suffering from uncomplicated malaria, are eligible for randomization.The study will be conducted in a total of 75 patients with uncomplicated malaria.

Detailed description: Approximately 75 patients will be randomized in a 1:2:2 ratio to 3 arms:

Arm 1: placebo+ACT group (15 patients)

Arm 2: 5 ALA/SFC+Placebo+ACT twice daily (BID) (30 patients)

Arm 3: 5-ALA/SFC+Placebo+ACT once daily (QD) (30 patients)

The study duration will be a maximum of 98 days with treatment period of 7 days and follow-up period of 91 days.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients of 18 to 60 years inclusive.
2. Weighing 35 to 90 kg.
3. Women with child bearing potential willing to give consent for pregnancy test.
4. Presence of symptomatic uncomplicated malaria of all species inclusive with a diagnosis confirmed by:

   A. Microscopically confirmed parasite infection, between 500 and 100,000 asexual parasite count/μL of blood.

   B. Fever, as defined by axillary/tympanic of ≥37.5°C within 24 hours before randomization (must be documented).
5. Patients must be willing and able to give written informed consent and comply with all study visits and procedures. If a patient cannot read informed consent and/or write a signature, an impartial witness who speaks the language of the patient must be present during the entire informed consent process and discussion with the patient.

Exclusion Criteria:

1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization (WHO) Criteria 2010.
2. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment.
3. Known history of photo-hypersensitivity, porphyria, or hemochromatosis.
4. Have taken any medication with antimalarial or antibiotic with antimalarial effect within 14 days before randomization.
5. Received an investigational drug within the past 28 days.
6. Patients whose Hemoglobin (Hb) level is lower than 8 g/dL.
7. Liver function tests (aspartate aminotransferase/alanine aminotransferase \[AST/ALT\] levels) more than 2.5 times upper limit of normal values.
8. Known human immunodeficiency virus (HIV) or Hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive, testing is not required.
9. Known significant renal impairment as indicated by serum creatinine of ≥1.4 mg/dL or estimated glomerular filtration rate (eGFR) of \<45 mL/min.
10. Known history of hypersensitivity, allergic or adverse reactions to 5-aminolevulinic acid and sodium ferrous citrate.
11. Presence or history of uncontrolled systemic disease.
12. Female patients who are pregnant or breast-feeding.
13. Any other condition in the opinion of the investigator makes the patient unsuitable for study
14. Received any medication specified as contraindication for ACT or affecting blood concentration of ACT within 5 times the half-life of each medication before the first dose of study medication.

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: From screening visit (Day -1) untill the Follow-up Visit (Day 98)
measure: Cure rate on Day 28
timeFrame: Day 28
measure: Parasite Clearance Time
timeFrame: Every 4 hours for 72 hours from Day 1 to Day 7 until 4 consecutive negative readings
measure: Fever Reduction Time
timeFrame: Every 4 hours for 72 hours from Day 1 to Day 7
measure: Gametocyte Clearance Time
timeFrame: Day 1 to Day 7 + 24 hours
measure: Change in inflammatory parameter: C-reactive protein
timeFrame: Days 1, 3, 7, and 28
measure: Change in inflammatory parameter: interleukin-6
timeFrame: Days 1, 3, 7, and 28
measure: Change in inflammatory parameter: tumor necrosis factor (TNF)-alpha
timeFrame: Days 1, 3, 7, and 28
measure: Change in iron metabolism: Serum iron
timeFrame: Days 1, 3, 7, 28, and 98
measure: Change in iron metabolism: Hepcidin
timeFrame: Days 1, 3, 7, 28, and 98
measure: Change in iron metabolism: total iron binding capacity (TIBC)
timeFrame: Days 1, 3, 7, 28, and 98
measure: Change in iron metabolism: unsaturated iron binding capacity (UIBC)
timeFrame: Days 1, 3, 7, 28, and 98
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
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