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.
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.
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
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).
7. Radiographic evidence (chest X-ray or chest CT scan) of pulmonary infiltrates
8. 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
Bahrain Defense Force Royal Medical Services, Military Hospital
Manama, Bahrain
Salmaniya Medical Complex
Manama, Bahrain
Abdullah Darwish, Dr, Principal Investigator
Bahrain Defense Force Royal Medical Services, Military Hospital