Skip to main content
OpenTrials
Completed

NCT Number: NCT04542850

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

SARS-CoV 2 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

21 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Bahrain Defense Force Royal Medical Services, Military Hospital, Manama, Bahrain

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
  • Aged ≥ 21 to 70 years
  • Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test before beginning study dose regime
  • qSOFA ≥ 1
  • Currently hospitalized
  • 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).

  • Radiographic evidence (chest X-ray or chest CT scan) of pulmonary infiltrates
  • Able to swallow 5 capsules of study product at dosing time points.

Exclusion criteria

  • 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.
  • Subject is nourished via a nasogastric tube
  • Subject has acute or chronic type(s) of porphyria or a family history of porphyria
  • Subject has demonstrated previous intolerance of 5-ALA and/or SFC by topical or oral administration (except for photosensitivity)
  • Pregnant or nursing women
  • Males and females of reproductive potential who have not agreed to use an
  • 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
  • Subjects who are unable or unwilling to comply with requirements of the clinical trial
  • Participation in any other clinical trial of an experimental treatment for COVID-19
  • Evidence of multiorgan failure
  • Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
  • Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976}
  • Any other reason that makes the subject unsuitable in the Investigator's opinion

Treatment and study plan

5-ALA-Phosphate + SFC (5-ALA + SFC)

Dietary Supplement

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

Primary outcomes

  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).

    Time frame: 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 outcomes

  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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: day 14 and day 28

    To describe time until death from any cause

  5. Results of investigator´s assessment of patient´s oxygen therapy

    Time frame: 28 days

    To describe patient´s blood oxygenation

  6. Results of mechanical ventilation settings

    Time frame: 28 days

    To describe mechanical ventilation settings course during study.

  7. Results of duration of ventilation

    Time frame: 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

    Time frame: 28 days

    To describe patient´s specific symptoms course during study.

  9. Results of patient´s oxygen saturation (respiratory parameters)

    Time frame: 28 days

    To describe patient´s oxygen saturation course during study.

  10. Length of hospitalization

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: day 7, 14 and 28

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

  17. Results of patient´s Procalcitonin level.

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

    Time frame: 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.

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 28 days

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

  44. Results on patient´s Care Level

    Time frame: 28 days

    To describe patient´s care level course during study.

  45. Results on patient´s Mean arterial pressure(MAP)

    Time frame: 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)

    Time frame: 28 days

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

  47. Results on patient´s respiratory rate (RR)

    Time frame: 28 days

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

  48. Results on patient´s 12-lead ECG

    Time frame: day 0, 7, 14 and 28

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

  49. Organ damage

    Time frame: 28 days

    To describe patient´s organ damage status during the study

Sponsors and collaborators

Lead sponsor

Royal College of Surgeons in Ireland - Medical University of Bahrain

Other

Collaborators

  • Bahrain Defence Force Hospital
  • Salmaniya Medical Complex

Registry information

Official study 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)

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Sep 9, 2020
Registry last updated
Feb 9, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.