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

NCT ID: NCT04020653

Last Updated: 2020-03-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-06
• Study Completion Date: 2020-09-30

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo + ACT

Patients will receive placebo for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3.

Group Type: PLACEBO_COMPARATOR

Artemisinin-based combination (ACT)

Intervention Type: DRUG

Tablets of ACT will be administered following Dosage and Administration in the package insert of ACT. ACT will be supplied as a combination tablet.

Placebo

Intervention Type: DRUG

Matching placebo capsules to 5-ALA HCl and SFC will be administered to the patients

5 ALA/SFC+placebo+ACT BID

5-ALA HCl 300 mg and SFC 236 mg will be administered BID for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3.

Patients will receive 5-ALA HCl+Placebo and SFC+Placebo at odd number of study medication dosing (Dose 1, 3, 5, 7, 9, 11, 13) and only 5-ALA HCl and SFC at even numbers of study medication dosing (Dose 2, 4, 6, 8, 10,12, 14).

Group Type: EXPERIMENTAL

Artemisinin-based combination (ACT)

Intervention Type: DRUG

Tablets of ACT will be administered following Dosage and Administration in the package insert of ACT. ACT will be supplied as a combination tablet.

Placebo

Intervention Type: DRUG

Matching placebo capsules to 5-ALA HCl and SFC will be administered to the patients

5-aminolevulinic acid hydrochloride (5-ALA HCl) 300 mg BID

Intervention Type: DRUG

5-ALA HCl 150 mg capsules will be given to the patients as 300 mg BID

Sodium ferrous citrate (SFC) 236 mg BID

Intervention Type: DRUG

SFC 118 mg capsules will be given to the patients as 236 mg BID

5-ALA/SFC+placebo+ACT QD

5-ALA HCl 600 mg and SFC 472 mg will be administered QD in the morning or evening for Day 1 to Day 7 and ACT (as per package instruction) for Day 1 to Day 3. Patients will receive 5-ALA HCl and SFC at odd number of study medication dosing (Dose 1, 3, 5, 7) and placebo at even numbers of study medication dosing (Dose 2, 4, 6).

Group Type: EXPERIMENTAL

5-aminolevulinic acid hydrochloride (5-ALA HCl) 600 mg QD

Intervention Type: DRUG

5-ALA HCl 150 mg capsules will be given to the patients as 600 mg QD

Sodium ferrous citrate (SFC) 472 mg QD

Intervention Type: DRUG

SFC 118 mg capsules will be given to the patients as 472 mg QD

Artemisinin-based combination (ACT)

Intervention Type: DRUG

Tablets of ACT will be administered following Dosage and Administration in the package insert of ACT. ACT will be supplied as a combination tablet.

Placebo

Intervention Type: DRUG

Matching placebo capsules to 5-ALA HCl and SFC will be administered to the patients

Interventions

5-aminolevulinic acid hydrochloride (5-ALA HCl) 600 mg QD

5-ALA HCl 150 mg capsules will be given to the patients as 600 mg QD

Intervention Type: DRUG

Sodium ferrous citrate (SFC) 472 mg QD

SFC 118 mg capsules will be given to the patients as 472 mg QD

Intervention Type: DRUG

Artemisinin-based combination (ACT)

Tablets of ACT will be administered following Dosage and Administration in the package insert of ACT. ACT will be supplied as a combination tablet.

Intervention Type: DRUG

Placebo

Matching placebo capsules to 5-ALA HCl and SFC will be administered to the patients

Intervention Type: DRUG

5-aminolevulinic acid hydrochloride (5-ALA HCl) 300 mg BID

5-ALA HCl 150 mg capsules will be given to the patients as 300 mg BID

Intervention Type: DRUG

Sodium ferrous citrate (SFC) 236 mg BID

SFC 118 mg capsules will be given to the patients as 236 mg BID

Intervention Type: DRUG

Other Intervention Names

Artemether 20 mg and lumefantrine 120 mg

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

Neopharma Japan Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

NPJ005-MAL-0122

Identifier Type: -

Identifier Source: org_study_id