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

• ClinicalTrials.gov Identifier: NCT04762628
• Recruitment Status: Completed
• First Posted: February 21, 2021
• Last Update Posted: February 27, 2023
• Sponsor: Saisei Pharma
• Information provided by (Responsible Party): Saisei Pharma

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Dietary Supplement: MAF capsules 148 mg; Dietary Supplement: M capsules 148 mg; Other: Standard of care	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 27, 2020
• Actual Primary Completion Date: July 5, 2021
• Actual Study Completion Date: August 6, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The time to basic clinical improvement and to recovery defined as the following [ Time Frame: Day 1 through Day 29 ]
   • 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
2. 14-day Participant Mortality [ Time Frame: Day 1 through Day 14 ]
   The mortality rate will be determined as the proportion of participants who died by study Day 14
3. 29-day Participant Mortality [ Time Frame: Day 1 through Day 29 ]
   The mortality rate will be determined as the proportion of participants who died by study Day 29

Secondary Outcome Measures :

1. Percentage of Participants in Each Clinical Status Category as Assessed by a 9-Point Ordinal Scale on Day 14 [ Time Frame: 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
2. Time to an improvement of one category from admission on 9-Point Ordinal Scale [ Time Frame: Day 1 through Day 29 ]
   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
3. Time to an improvement of two categories from admission on 9-Point Ordinal Scale [ Time Frame: Day 1 through Day 29 ]
   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
4. 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 [ Time Frame: 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
5. Mean change in the ranking on 9-Point Ordinal Scale from baseline to days 3, 5, 8, 11, 14 and 29 [ Time Frame: 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
6. Duration of conventional oxygen therapy Use [ Time Frame: Day 1 through Day 29 ]
   Duration of conventional oxygen therapy use measured in days among participants who were on conventional oxygen therapy use at baseline
7. Duration of new conventional oxygen therapy use [ Time Frame: Day 1 through Day 29 ]
   Duration of new conventional oxygen therapy use measured in days among participants who were not on conventional oxygen therapy use at baseline
8. Duration of Non-invasive Ventilation or High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
   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
9. Duration of New Non-invasive Ventilation or High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
   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
10. Duration of Mechanical Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    Duration of Mechanical Ventilator or ECMO Use in days among all participants to whom it will be administrated
11. Percentage of Participants Requiring New Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    The percentage of participants requiring new oxygen determined as the percentage of participants not requiring oxygen at baseline
12. Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    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.
13. Percentage of Participants Requiring Ventilator or ECMO Use [ Time Frame: Day 1 through Day 29 ]
    The percentage of participants requiring Ventilator or ECMO Use
14. Incidents of post-COVID-19 related symptoms at Day 29 [ Time Frame: Day 29 ]
    Incidents of all post-COVID-19 symptoms, which will be reported in the post-COVID-19 questionnaire form
15. Incidents of post-COVID-19 related symptoms at Day 60 [ Time Frame: Day 60 ]
    Incidents of all post-COVID-19 symptoms, which will be reported in the post-COVID-19 questionnaire form
16. Percentage of participants with post-COVID-19 related symptoms at Day 29 [ Time Frame: Day 29 ]
    Percentage of participants with presents post-COVID-19 related symptoms
17. Percentage of participants with post-COVID-19 related symptoms at Day 60 [ Time Frame: Day 60 ]
    Percentage of participants with presents post-COVID-19 related symptoms
18. Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) [ Time Frame: Day 1 through Day 29 ]
    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.
19. Percentage of Participants Reporting Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 29 ]
    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.
20. Percentage of Participants Discontinued or Temporarily Suspended From Investigational dietary supplements [ Time Frame: Day 1 through Day 14 ]
    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.
21. Change From Baseline in Alanine Transaminase (ALT) [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
22. Change From Baseline in Aspartate Transaminase (AST) [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
23. Change From Baseline in Total Bilirubin [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
24. Change From Baseline in Creatinine [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
25. Change From Baseline in Glucose [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
26. Change From Baseline in Hemoglobin [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
27. Change From Baseline in Platelets [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
28. Change From Baseline in White Blood Cell Count (WBC) [ Time Frame: Days 1, 7, 14 and 29 ]
    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.
29. Change From Baseline in Lymphocytes [ Time Frame: Days 1, 7, 14 and 29 ]
    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.

Other Outcome Measures:

1. Change From Baseline in C-Reactive Protein [ Time Frame: Days 1, 7 and 14 ]
   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
2. Change From Baseline in D-Dimer [ Time Frame: Days 1, 7 and 14 ]
   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
3. Change From Baseline in Lactate Dehydrogenase [ Time Frame: Days 1, 7 and 14 ]
   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
4. Change From Baseline in Ferritin [ Time Frame: Days 1, 7 and 14 ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Ukraine

The Central Hospital of Rubizhne, Infection Disease Department

Rubizhne, Luhansk Region, Ukraine, 93012

Municipal Kharkiv Regional Infectious Diseases Clinical Hospital

Kharkiv, Ukraine, 61000

Sponsors and Collaborators

Saisei Pharma

More Information

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.

• Responsible Party: Saisei Pharma
• ClinicalTrials.gov Identifier: NCT04762628
• Other Study ID Numbers: SaiseiMAF supplements COVID
• First Posted: February 21, 2021
• Last Update Posted: February 27, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data will be shared via ISARIC COVID-19 Clinical Database.
• Time Frame: Request for data will be indefinitely available
• Access Criteria: Reasonable request to investigators

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Saisei Pharma:

Covid19; Colostrum MAF; Supplements; Oxygen supply; Mortality; Clinical improvement; lymphocyte depletion prevention

Additional relevant MeSH terms:

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