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)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- 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).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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
结局指标
主要结局
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).
时间窗: 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.
次要结局
- Results on patient´s Lymphocyte(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Mean arterial pressure(MAP)(28 days)
- Results of patient´s D-Dimer parameter(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s Procalcitonin level.(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- The total time in ICU(From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28)
- Results of patient´s PT parameter(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s Serum Ferritin level(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s T helper cells (CD4/CD8) level.(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Platelets(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of mechanical ventilation settings(28 days)
- Results of duration of ventilation(from date of enrolment until the extubation or until last 5-ALA- Phosphate -SFC administration on day 28)
- Length of hospitalization(From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28)
- Results of investigator´s assessment of patient´s condition using (q)SOFA score(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s IL-6 level(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s urine(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s heart rate (HR)(28 days)
- The time to resolution of patient´s symptoms(28 days)
- Results of patient´s PTT parameter(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s SARS-CoV-2 viral load status (efficacy)(day 7, 14 and 28)
- Results of patient´s C-Reactive protein (CRP) level(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results of patient´s Bilirubin level.(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Neutrophils(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s ALT(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Total bilirubin(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Creatinine kinase(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on hepatic function(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- 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)
- 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)
- Patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized(28 days)
- Overall survival(day 14 and day 28)
- Results of investigator´s assessment of patient´s oxygen therapy(28 days)
- Results of patient´s oxygen saturation (respiratory parameters)(28 days)
- Results on patient´s renal function(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Leucocytes(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Serum creatinine(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Myoglobin glucose(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s iron parameters(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Co-infections(28 days)
- Results on patient´s 12-lead ECG(day 0, 7, 14 and 28)
- Organ damage(28 days)
- Results on patient´s AST(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s aPTT(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s physical examination(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Care Level(28 days)
- Results on patient´s Hemoglobin(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Albumin(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s Blood urea nitrogen(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s LDH(day 0, 2, 3, 5, 7, 10, 14, 21, 28)
- Results on patient´s respiratory rate (RR)(28 days)