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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04020653
• Other study ID #: NPJ005-MAL-0122
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 6, 2019
• Est. completion date: September 30, 2020

Study information

• Verified date: February 2020
• Source: Neopharma Japan Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 30, 2020
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• 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
• Sodium ferrous citrate (SFC) 472 mg QD
SFC 118 mg capsules will be given to the patients as 472 mg QD
• 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.
• Placebo
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
5-ALA HCl 150 mg capsules will be given to the patients as 300 mg BID
• Sodium ferrous citrate (SFC) 236 mg BID
SFC 118 mg capsules will be given to the patients as 236 mg BID

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Neopharma Japan Co., Ltd.	Parexel

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events	Number of patients with any adverse events or clinically significant abnormal laboratory parameters to investigate safety and tolerability of 5-ALA HCl and SFC in simultaneous administration with ACT.	From screening visit (Day -1) untill the Follow-up Visit (Day 98)
Primary	Cure rate on Day 28	Cure rate is defined as the proportion of patients with polymerase chain reaction (PCR)-corrected Adequate Clinical and Parasitological Response (ACPR). PCR-corrected ACPR is defined as patients with clearance of asexual parasites within 28 days of initiation of study medication and without recrudescence within 28 days. Cure rate to investigate the preliminary efficacy of 5-ALA HCl and SFC in simultaneous administration with ACT.	Day 28
Primary	Parasite Clearance Time	Time from first dosing to time of first of 4 consecutive readings with zero parasite count in blood. Calculated based on parasite count in blood every 4 hours after the start of study medication for 72 hours until there are 4 consecutive negative readings.	Every 4 hours for 72 hours from Day 1 to Day 7 until 4 consecutive negative readings
Primary	Fever Reduction Time	Time to Fever Reduction is defined as the time from first dosing to first normal reading of temperature (<37.5 °C) for two consecutive normal temperature reading plus confirmed normal temperature every 4 hours after the start of study medication for 72 hours	Every 4 hours for 72 hours from Day 1 to Day 7
Primary	Gametocyte Clearance Time	Time from the first dose until first total and continued disappearance of gametocytes which remains at least a further 24 hours	Day 1 to Day 7 + 24 hours
Primary	Change in inflammatory parameter: C-reactive protein	Change from baseline in C-reactive protein to investigate change in inflammatory parameters	Days 1, 3, 7, and 28
Primary	Change in inflammatory parameter: interleukin-6	Change from baseline in interleukin-6 to investigate change in inflammatory parameters	Days 1, 3, 7, and 28
Primary	Change in inflammatory parameter: tumor necrosis factor (TNF)-alpha	Change from baseline in tumor necrosis factor (TNF)-alpha to investigate change in inflammatory parameters	Days 1, 3, 7, and 28
Primary	Change in iron metabolism: Serum iron	Change from baseline in serum iron to investigate change in iron metabolism parameters	Days 1, 3, 7, 28, and 98
Primary	Change in iron metabolism: Hepcidin	Change from baseline in hepcidin to investigate change in iron metabolism parameters	Days 1, 3, 7, 28, and 98
Primary	Change in iron metabolism: total iron binding capacity (TIBC)	Change from baseline in total iron binding capacity (TIBC) to investigate change in iron metabolism parameters	Days 1, 3, 7, 28, and 98
Primary	Change in iron metabolism: unsaturated iron binding capacity (UIBC)	Change from baseline in unsaturated iron binding capacity (UIBC) to investigate change in iron metabolism parameters	Days 1, 3, 7, 28, and 98