Trial Efficacy of Saisei Pharma Dietary Supplements MAF Capsules, 148 mg and M Capsules, 148 mg in Hospitalized COVID-19 Patients

Study Overview
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Brief Summary
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The SaiseiCovUKR clinical study is a multicentric, randomized trial study targeting patients hospitalized with COVID-19 who do not require mechanical ventilation. This study aims to provide preliminary data on the activity and safety of MAF capsules and M capsules in the target population after 14 days of dosing. MAF capsules and M capsules are dietary supplements targeting the gut's mucosal immunity to control local and systemic inflammation, limiting epithelial damage and preventing the accumulation of pathological macrophage populations at sites of SARS-CoV-2 infection.

Detailed Description
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Saisei Pharma is developing biologics using an enzymatic modification of Vitamin D binding protein and other glycoproteins in biological substrates, which have been shown to increase macrophage phagocytic and antigen processing activity without promoting the proinflammatory profile of macrophages. Bovine colostrum is the substrate for MAF capsules and bovine whey for M capsules. The enteric capsules formulation of the investigational dietary supplements is targeting the gut mucosa and its associated natural anti-inflammatory macrophages profile. The SaiseiCovUKR clinical study is multicentric, randomized, open-label in hospitalized patients with moderate and severe COVID-19 to provide data on the activity and safety of MAF capsules and M capsules in the target population after 14 days of dosing. The trial will use an adaptive design based on a pre-specified criteria, using an independent external Data Monitoring Committee (DMC) to monitor safety, efficacy, and review data at appropriate intervals. The general objectives of the study are to obtain a preliminary indication of activity of MAF capsules and M capsules on shortened time to recovery and decreased mortality in the target population (600 patients, age ≥ 18 years). The study results can provide a background for further investigation of the studied dietary supplements as new drugs in COVID-19.

Official Title
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Randomized Trial to Assess the Efficacy and Safety of Dietary Supplements MAF Capsules, 148 mg and M Capsules, 148 mg in Addition to the Standard of Care (SOC) Compared SOC in the Treatment of Hospitalized With COVID-19 Patients Who Not Requiring the Mechanical Ventilation

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: MAF capsules 148 mg
* Dietary Supplement: M capsules 148 mg
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients found to have positive RT-PCR for SARS-CoV-2 in any specimen on 4 days prior to randomization, those who are hospitalized with evidence of respiratory disease during clinical assessment or imaging Male or non-pregnant female adult ≥18 years of age subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures Subject (or legally authorized representative) understands and agrees to comply with planned study procedures Has illness of not more than 7 days duration At the time of enrolment does not require immediate resuscitation or mechanical ventilation Respiration rate ≤ 29 per minute SpO2 ≤ 95% on room air Agrees to not participate in another clinical trial through Day 29 Exclusion Criteria: Pregnant or breastfeeding women Known allergy to dairy products On corticosteroids for COVID-19 therapy at the time of screening Subjects who are taking corticosteroids or other immunosuppressive drugs for other medical conditions Concurrent malignancy requiring chemotherapy Known renal insufficiency with glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration). ALT or AST > 5 times the upper limit of normal Subjects receiving other immune-based therapy for COVID-19, such as convalescent plasma, immunoglobulin products, interferons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAF capsules<br>MAF capsules 148 mg TID for 14 days + Standard of care | Dietary Supplement: MAF capsules 148 mg<br>* enteric capsules based on enzymatically treated bovine colostrum<br>|
| Experimental: M capsules<br>M capsules 148 mg TID for 14 days + Standard of care | Dietary Supplement: M capsules 148 mg<br>* enteric capsules based on enzymatically treated bovine whey<br>|
| Active Comparator: Comparison<br>Standard of care | Other: Standard of care<br>* Standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to basic clinical improvement and to recovery defined as the following | Hospitalized, not requiring supplemental oxygen, requires ongoing medical care Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities | Day 1 through Day 29 | 
| 14-day Participant Mortality | The mortality rate will be determined as the proportion of participants who died by study Day 14 | Day 1 through Day 14 | 
| 29-day Participant Mortality | The mortality rate will be determined as the proportion of participants who died by study Day 29 | Day 1 through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Each Clinical Status Category as Assessed by a 9-Point Ordinal Scale on Day 14 | Clinical status derives from death, hospital discharge, and 9-Point Ordinal Scale as follows: score of 8 use for all days on or after the date of death; score of 0 use for all days on or after discharged alive date; last available assessment for missing value. The scale is as follows: 8. Death; 7. Hospitalized, on invasive mechanical ventilation with vasopressor or Extracorporeal Membrane Oxygenation; 6. Hospitalized, on invasive mechanical ventilation; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 3. Hospitalized, not requiring supplemental oxygen - requires ongoing medical care (coronavirus (COVID-19) related or otherwise; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 1. Not hospitalized, no limitation on activities; 0. No clinical or virological evidence of infection | Day 14 | 
| Time to an improvement of one category from admission on 9-Point Ordinal Scale | Time to reach an improvement of one category from admission on 9-Point Ordinal Scale. The scale is as follows: 8. Death; 7. Hospitalized, on invasive mechanical ventilation with vasopressor or Extracorporeal Membrane Oxygenation; 6. Hospitalized, on invasive mechanical ventilation; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 3. Hospitalized, not requiring supplemental oxygen - requires ongoing medical care (coronavirus (COVID-19) related or otherwise; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 1. Not hospitalized, no limitation on activities; 0. No clinical or virological evidence of infection | Day 1 through Day 29 | 
| Time to an improvement of two categories from admission on 9-Point Ordinal Scale | Time to reach an improvement of two categories from admission on 9-Point Ordinal Scale. The scale is as follows: 8. Death; 7. Hospitalized, on invasive mechanical ventilation with vasopressor or Extracorporeal Membrane Oxygenation; 6. Hospitalized, on invasive mechanical ventilation; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 3. Hospitalized, not requiring supplemental oxygen - requires ongoing medical care (coronavirus (COVID-19) related or otherwise; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 1. Not hospitalized, no limitation on activities; 0. No clinical or virological evidence of infection | Day 1 through Day 29 | 
| Percentage of Participants in Each Clinical Status Category as Assessed by a 9-Point Ordinal Scale on Day at days 3, 5, 8, 11,14 and 29 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8. Death; 7. Hospitalized, on invasive mechanical ventilation with vasopressor or Extracorporeal Membrane Oxygenation; 6. Hospitalized, on invasive mechanical ventilation; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 3. Hospitalized, not requiring supplemental oxygen - requires ongoing medical care (coronavirus (COVID-19) related or otherwise; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 1. Not hospitalized, no limitation on activities; 0. No clinical or virological evidence of infection | Days 3, 5, 8, 11,14 and 29 | 
| Mean change in the ranking on 9-Point Ordinal Scale from baseline to days 3, 5, 8, 11, 14 and 29 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8. Death; 7. Hospitalized, on invasive mechanical ventilation with vasopressor or Extracorporeal Membrane Oxygenation; 6. Hospitalized, on invasive mechanical ventilation; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 3. Hospitalized, not requiring supplemental oxygen - requires ongoing medical care (coronavirus (COVID-19) related or otherwise; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 1. Not hospitalized, no limitation on activities; 0. No clinical or virological evidence of infection | Days 3, 5, 8, 11, 14 and 29 | 
| Duration of conventional oxygen therapy Use | Duration of conventional oxygen therapy use measured in days among participants who were on conventional oxygen therapy use at baseline | Day 1 through Day 29 | 
| Duration of new conventional oxygen therapy use | Duration of new conventional oxygen therapy use measured in days among participants who were not on conventional oxygen therapy use at baseline | Day 1 through Day 29 | 
| Duration of Non-invasive Ventilation or High Flow Oxygen Use | Duration of non-invasive ventilation or high flow oxygen use measured in days among participants who were on non-invasive ventilation or high-flow oxygen use at baseline | Day 1 through Day 29 | 
| Duration of New Non-invasive Ventilation or High Flow Oxygen Use | Duration of new non-invasive ventilation or high flow oxygen use measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline | Day 1 through Day 29 | 
| Duration of Mechanical Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use | Duration of Mechanical Ventilator or ECMO Use in days among all participants to whom it will be administrated | Day 1 through Day 29 | 
| Percentage of Participants Requiring New Oxygen Use | The percentage of participants requiring new oxygen determined as the percentage of participants not requiring oxygen at baseline | Day 1 through Day 29 | 
| Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use | New non-invasive ventilation or high-flow oxygen use determined as the percentage of subjects not on non-invasive ventilation or high-flow oxygen at baseline. | Day 1 through Day 29 | 
| Percentage of Participants Requiring Ventilator or ECMO Use | The percentage of participants requiring Ventilator or ECMO Use | Day 1 through Day 29 | 
| Incidents of post-COVID-19 related symptoms at Day 29 | Incidents of all post-COVID-19 symptoms, which will be reported in the post-COVID-19 questionnaire form | Day 29 | 
| Incidents of post-COVID-19 related symptoms at Day 60 | Incidents of all post-COVID-19 symptoms, which will be reported in the post-COVID-19 questionnaire form | Day 60 | 
| Percentage of participants with post-COVID-19 related symptoms at Day 29 | Percentage of participants with presents post-COVID-19 related symptoms | Day 29 | 
| Percentage of participants with post-COVID-19 related symptoms at Day 60 | Percentage of participants with presents post-COVID-19 related symptoms | Day 60 | 
| Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) | Grade 3 AEs are defined as events interrupting daily living activities, or significantly affecting clinical status, or requiring intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as potentially life threatening. | Day 1 through Day 29 | 
| Percentage of Participants Reporting Serious Adverse Events (SAEs) | An SAE is defined as an AE or a suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. | Day 1 through Day 29 | 
| Percentage of Participants Discontinued or Temporarily Suspended From Investigational dietary supplements | Participants may have discontinued from investigational dietary supplements due to product intolerability, applied mechanical ventilation, swallowing impairment, or death. The discontinuation or temporary suspension intake of studied supplements for any reason will be collected. | Day 1 through Day 14 | 
| Change From Baseline in Alanine Transaminase (ALT) | To evaluate ALT, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Aspartate Transaminase (AST) | To evaluate AST, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Total Bilirubin | To evaluate Total Bilirubin, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Creatinine | To evaluate serum Creatinine, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Glucose | To evaluate serum Glucose, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Hemoglobin | To evaluate Hemoglobin, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Platelets | To evaluate Platelets, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in White Blood Cell Count (WBC) | To evaluate WBC, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 
| Change From Baseline in Lymphocytes | To evaluate Lymphocytes, blood will be collected at Days 1, 7, and 14 while participants are inpatient, and at Day 29, with the Day 1 assessment serving as the baseline. Participants who will be discharged will have blood collected if infection control measures allow in-person visits after discharge. | Days 1, 7, 14 and 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, lymphocyte depletion prevention, Colostrum MAF, Supplements, Oxygen supply, Mortality, Clinical improvement