Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-ALA-Phosphate + SFC in Subjects With COVID-19

Sponsor
Royal College of Surgeons in Ireland - Medical University of Bahrain (Other)
Overall Status
Completed
CT.gov ID
NCT04542850
Collaborator
Bahrain Defence Force Hospital (Other), Salmaniya Medical Complex (Other)
15
Enrollment
2
Locations
1
Arm
11.4
Actual Duration (Months)
7.5
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19) involving 40 subjects.

The primary objective is to evaluate the safety of 4-week oral administration of 5-ALAPhosphate + SFC. This study is expected to last for 4 weeks and will include follow-up until day 28 in the hospital or in an outpatient setting if the subjects are discharged earlier.

Condition or DiseaseIntervention/TreatmentPhase
  • Dietary Supplement: 5-ALA-Phosphate + SFC (5-ALA + SFC)
N/A

Detailed Description

This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19).

Heme is critical for appropriate oxygen binding and delivery to remote site and without the heme contained within the hemoglobin tetramer, multicellular organisms would be unable to survive. Furthermore HO-1 degrades heme into biliverdin, carbon monoxide (CO), and iron, and biliverdin is immediately reduced and turned into bilirubin by biliverdin reductase. Biliverdin/bilirubin and CO both have anti-oxidative functions and they regulate important biological processes like inflammation, apoptosis, cell proliferation, fibrosis, and angiogenesis. Therefore, HO-1 is deemed to be a promising drug target (Ryter 2006). HO-1 is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance. 5-ALA-Phosphate + SFC increases heme metabolism and HO-1 via enhancement of porphyrin biology and utilizes the HO-1 for endothelial pacification strategy.

The primary endpoints of this study is- all treatment emergent AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA-Phosphate + SFC. 40 subjects with symptoms requiring hospitalization will be enrolled in thestudy, with 20 subjects enrolled in each group below:

Group 1: 20 Moderately ill hospitalized subjects not requiring assisted ventilation Group 2:

20 Severely ill hospitalized subjects requiring assisted ventilation

The duration of this clinical study will be 4 weeks, and follow-up will be performed until Day 28 in hospital, or in an outpatient setting if subjects improve and are discharged home or to alternative care facility.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is an open label pilot study involving 40 patients with COVID-19 disease. Patients that are hospitalized due to confirmed SARS-CoV-2 infection will be assigned to two groups according o their severity grade (moderate or severe).This is an open label pilot study involving 40 patients with COVID-19 disease. Patients that are hospitalized due to confirmed SARS-CoV-2 infection will be assigned to two groups according o their severity grade (moderate or severe).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-Aminolevulinic Acid Phosphate and Sodium Ferrous Citrate (5-ALA-Phosphate + SFC) in Subjects With SARS-CoV-2 Infection (COVID-19)
Actual Study Start Date :
Nov 15, 2020
Actual Primary Completion Date :
Aug 31, 2021
Actual Study Completion Date :
Oct 28, 2021

Arms and Interventions

ArmIntervention/Treatment
Other: Moderate group and Severe Group

Moderate group and Severe group - . Both groups will be administered 5-aminolevulinic acid (5-ALA) is a natural delta amino acid widely present in nature that can be found in common food. 5-ALA combined with sodium ferrous citrate (SFC) produces the nutritional dietary supplement 5-ALA-Phosphate + SFC (5-ALA + SFC).

Dietary Supplement: 5-ALA-Phosphate + SFC (5-ALA + SFC)
Moderately ill hospitalized patients will receive: 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) two times daily (resulting in 500 mg 5-ALA-Phosphate and 286.8 mg SFC (30.4 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days Severely ill hospitalized patients will receive: 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) three times daily (resulting in 750 mg 5-ALA-Phosphate and 430.2 mg SFC (45.6 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days

Outcome Measures

Primary Outcome Measures

  1. The incidence of treatment emergent Adverse Events (safety and tolerability) of 5-ALA-Phospate + SFC in patients with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19). [28 days]

    To describe the incidence of treatment-emergent Adverse Events (TEAEs) of CTC Grades III and IV within four weeks following base line dose.

Secondary Outcome Measures

  1. Sum COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for Moderate group and for Severe group [28 days]

    To describe patient's condition in Moderate and Severe group using average, median, minimum and maximum in COVID-19 Modified Ordinal Scale for Clinical Improvement score.

  2. Rate of change in COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for individual subjects in Moderate group and in Severe group [28 days]

    To describe patient´s condition in Moderate and Severe Group using rate of change in COVID-19 Modified Ordinal Scale for Clinical Improvement score.

  3. Patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized [28 days]

    To describe patient´s condition in Moderate and Severe Group using patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized.

  4. Overall survival [day 14 and day 28]

    To describe time until death from any cause

  5. Results of investigator´s assessment of patient´s oxygen therapy [28 days]

    To describe patient´s blood oxygenation

  6. Results of mechanical ventilation settings [28 days]

    To describe mechanical ventilation settings course during study.

  7. Results of duration of ventilation [from date of enrolment until the extubation or until last 5-ALA- Phosphate -SFC administration on day 28]

    To describe duration of patient´s ventilation

  8. The time to resolution of patient´s symptoms [28 days]

    To describe patient´s specific symptoms course during study.

  9. Results of patient´s oxygen saturation (respiratory parameters) [28 days]

    To describe patient´s oxygen saturation course during study.

  10. Length of hospitalization [From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28]

    To describe duration of hospitalization in the patient groups.

  11. The total time in ICU [From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28]

    To describe duration of residence in ICU in the patient groups.

  12. Results of investigator´s assessment of patient´s condition using (q)SOFA score [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe patient´s (q)SOFA score course during study.

  13. Results of patient´s PT parameter [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe patient´s coagulation function course during study which by evaluating the PT value.

  14. Results of patient´s D-Dimer parameter [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe patient´s coagulation function course during study which by evaluating the D-Dimer value.

  15. Results of patient´s PTT parameter [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe patient´s coagulation function course during study which by evaluating the PTT value.

  16. Results of patient´s SARS-CoV-2 viral load status (efficacy) [day 7, 14 and 28]

    To describe patient's SARS-CoV-2 viral load course during study.

  17. Results of patient´s Procalcitonin level. [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the Procalcitonin value.

  18. Results of patient´s IL-6 level [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the IL-6 value.

  19. Results of patient´s Serum Ferritin level [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the Serum ferritin value.

  20. Results of patient´s C-Reactive protein (CRP) level [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the C-Reactive protein (CRP) value.

  21. Results of patient´s T helper cells (CD4/CD8) level. [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the T helper cells (CD4/CD8) value.

  22. Results of patient´s Bilirubin level. [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe infection parameter course of each patient during study by evaluating the Bilirubin value.

  23. Results on patient´s Leucocytes [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Leucocytes value

  24. Results on patient´s Neutrophils [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Neutrophils value

  25. Results on patient´s Lymphocyte [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Lymphocyte value

  26. Results on patient´s Platelets [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Platelets value

  27. Results on patient´s Hemoglobin [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Hemoglobin value

  28. Results on patient´s Albumin [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Albumin value

  29. Results on patient´s AST [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating AST value

  30. Results on patient´s ALT [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating ALT value

  31. Results on patient´s Total bilirubin [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Total bilirubin value

  32. Results on patient´s Blood urea nitrogen [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Blood urea nitrogen value

  33. Results on patient´s Serum creatinine [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Serum creatinine value

  34. Results on patient´s Creatinine kinase [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Creatinine kinase value

  35. Results on patient´s LDH [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating LDH value

  36. Results on patient´s Myoglobin glucose [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating Myoglobin glucose value

  37. Results on patient´s aPTT [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating aPTT value

  38. Results on patient´s urine [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating urinalysis (urine test strip)

  39. Results on hepatic function [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating hepatic function

  40. Results on patient´s renal function [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating renal function

  41. Results on patient´s iron parameters [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe laboratory assessments course during study by evaluating iron parameters

  42. Results on patient´s physical examination [day 0, 2, 3, 5, 7, 10, 14, 21, 28]

    To describe patient´s conditions course during study using physical examination which include General Appearance, ENT, Respiratory, Cardiovascular, Musculoskeletal, Skin and Neurological.

  43. Results on patient´s Co-infections [28 days]

    To describe patient's Co-infections course during study.

  44. Results on patient´s Care Level [28 days]

    To describe patient´s care level course during study.

  45. Results on patient´s Mean arterial pressure(MAP) [28 days]

    To describe patient´s vital signs course during study by evaluating Mean arterial pressure(MAP)

  46. Results on patient´s heart rate (HR) [28 days]

    To describe patient´s vital signs course during study by evaluating heart rate (HR)

  47. Results on patient´s respiratory rate (RR) [28 days]

    To describe patient´s vital signs course during study by evaluating respiratory rate (RR)

  48. Results on patient´s 12-lead ECG [day 0, 7, 14 and 28]

    To describe patient´s 12-lead ECG result course during study.

  49. Organ damage [28 days]

    To describe patient´s organ damage status during the study

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent

  2. Aged ≥ 21 to 70 years

  3. Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test before beginning study dose regime

  4. qSOFA ≥ 1

  5. Currently hospitalized

  6. Moderate COVID-19 patients should meet any of the following criteria:

evidence of lower respiratory disease by clinical assessment (qSOFA ≥ 1or imaging) and saturation of oxygen (SpO2) ≥94% on room air at sea level.

Severe COVID-19 patients should meet any of the following criteria: a respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, and lung infiltrates >50% (if possible to measure). In exceptional cases the investigator can decide due to certain signs and symptoms to assign a moderate patient to the severe group although not all criteria mentioned before are fulfilled (to be documented with explanation).

  1. Radiographic evidence (chest X-ray or chest CT scan) of pulmonary infiltrates

  2. Able to swallow 5 capsules of study product at dosing time points.

Exclusion Criteria:
  1. Subject has critical symptoms of COVID19 infection as defined as: high-flow oxygen therapy (>15 l/min delivered by nasal cannula or mask) or invasive mechanical ventilation signifying respiratory failure, septic shock, and/or multiple organ dysfunction ventilation at screening.

  2. Subject is nourished via a nasogastric tube

  3. Subject has acute or chronic type(s) of porphyria or a family history of porphyria

  4. Subject has demonstrated previous intolerance of 5-ALA and/or SFC by topical or oral administration (except for photosensitivity)

  5. Pregnant or nursing women

  6. Males and females of reproductive potential who have not agreed to use an

  7. adequate method of contraception during the study For females, adequate birth control methods will be defined as: hormonal contraceptives, intrauterine device or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam For males, adequate birth control methods will be defined as double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam For females, menopause is defined as one year without menses; if in question, a folliclestimulating hormone of >40 U/ml must be documented. Hysterectomy, bilateral oophorectomy,or bilateral tubal ligation must be documented, as applicable

  8. Subjects who are unable or unwilling to comply with requirements of the clinical trial

  9. Participation in any other clinical trial of an experimental treatment for COVID-19

  10. Evidence of multiorgan failure

  11. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)

  12. Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976}

  13. Any other reason that makes the subject unsuitable in the Investigator's opinion

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Bahrain Defense Force Royal Medical Services, Military HospitalManamaBahrain
2Salmaniya Medical ComplexManamaBahrain

Sponsors and Collaborators

  • Royal College of Surgeons in Ireland - Medical University of Bahrain
  • Bahrain Defence Force Hospital
  • Salmaniya Medical Complex

Investigators

  • Principal Investigator: Abdullah Darwish, Dr, Bahrain Defense Force Royal Medical Services, Military Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Royal College of Surgeons in Ireland - Medical University of Bahrain
ClinicalTrials.gov Identifier:
NCT04542850
Other Study ID Numbers:
  • 68 / 02-Aug-2020
First Posted:
Sep 9, 2020
Last Update Posted:
Feb 9, 2022
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Royal College of Surgeons in Ireland - Medical University of Bahrain
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 9, 2022