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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Other: Standard of care; Dietary supplement: MAF capsules 148 mg; Dietary supplement: M capsules 148 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ukraine
  • Kharkiv, Ukraine, 61000
    • Municipal Kharkiv Regional Infectious Diseases Clinical Hospital
  • Luhansk Region
    • Rubizhne, Luhansk Region, Ukraine, 93012
      • The Central Hospital of Rubizhne, Infection Disease Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. 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
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures
4. Has illness of not more than 7 days duration
5. At the time of enrolment does not require immediate resuscitation or mechanical ventilation
6. Respiration rate ≤ 29 per minute
7. SpO2 ≤ 95% on room air
8. Agrees to not participate in another clinical trial through Day 29

Exclusion Criteria:

1. Pregnant or breastfeeding women
2. Known allergy to dairy products
3. On corticosteroids for COVID-19 therapy at the time of screening
4. Subjects who are taking corticosteroids or other immunosuppressive drugs for other medical conditions
5. Concurrent malignancy requiring chemotherapy
6. Known renal insufficiency with glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).
7. ALT or AST > 5 times the upper limit of normal
8. Subjects receiving other immune-based therapy for COVID-19, such as convalescent plasma, immunoglobulin products, interferons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MAF capsules; MAF capsules 148 mg TID for 14 days + Standard of care	Dietary supplement: MAF capsules 148 mg; enteric capsules based on enzymatically treated bovine colostrum
Experimental: M capsules; M capsules 148 mg TID for 14 days + Standard of care	Dietary supplement: M capsules 148 mg; enteric capsules based on enzymatically treated bovine whey
Active Comparator: Comparison; Standard of care	Other: Standard of care; Standard of care

What is the study measuring?

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
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 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 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
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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in C-Reactive Protein	To evaluate C-Reactive Protein, blood will be collected at Days 1, 7 and 14 while participants are inpatient, 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 and 14
Change From Baseline in D-Dimer	To evaluate D-Dimer, blood will be collected at Days 1, 7 and 14 while participants are inpatient, 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 and 14
Change From Baseline in Lactate Dehydrogenase	To evaluate Lactate Dehydrogenase, blood will be collected at Days 1, 7 and 14 while participants are inpatient, 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 and 14
Change From Baseline in Ferritin	To evaluate Ferritin, blood will be collected at Days 1, 7 and 14 while participants are inpatient, 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 and 14

Collaborators and Investigators

• Sponsor: Saisei Pharma

Publications and helpful links

General Publications

• Kawakatsu K, Ishikawa M, Mashiba R, Tran NK, Akamatsu M, Nishikata T. Characteristic Morphological Changes and Rapid Actin Accumulation in Serum-MAF-treated Macrophages. Anticancer Res. 2019 Aug;39(8):4533-4537. doi: 10.21873/anticanres.13630.
• Uto Y, Kawai T, Sasaki T, Hamada K, Yamada H, Kuchiike D, Kubo K, Inui T, Mette M, Tokunaga K, Hayakawa A, Go A, Oosaki T. Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. Anticancer Res. 2015 Aug;35(8):4487-92.
• Greilberger J, Herwig R. Vitamin D - Deglycosylated Vitamin D Binding Protein Dimer: Positive Synergistic Effects on Recognition, Activation, Phagocytosis and Oxidative Stress on Macrophages. Clin Lab. 2020 Jan 1;66(1). doi: 10.7754/Clin.Lab.2019.191121.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Actual): July 5, 2021
• Study Completion (Actual): August 6, 2021

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Covid19; Mortality; Supplements; Colostrum MAF; Oxygen supply; Clinical improvement; lymphocyte depletion prevention
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: SaiseiMAF supplements COVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be shared via ISARIC COVID-19 Clinical Database.
• IPD Sharing Time Frame: Request for data will be indefinitely available
• IPD Sharing Access Criteria: Reasonable request to investigators

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No