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Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease (COVID-19_LF)

Primary Purpose

Corona Virus Infection, Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome

Status
Not yet recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Lactoferrin (Apolactoferrin)
Placebo of excipient(s) will be administered
Sponsored by
National Research Centre, Egypt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection focused on measuring Lactoferrin, Apolactoferrin, Immuno-modulatory, Cytokine-storm, Antiviral, 2019nCoV, 2019 new coronavirus (2019nCoV), Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome (ARDS), COVID-19, SARS-CoV 2

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients tested positive (PCR) for SARS-CoV-2 and clinically symptomatic.
  • Adult patients with age >18 years.
  • Patients willing and able to sign the study informed consent form.

Exclusion Criteria:

  • Critically severe disease patients (having Respiratory failure requiring mechanical ventilation, or signs of septic shock or multiple organ failure requiring ICU admission).
  • Patients who are unconscious
  • Patients who have convulsions
  • Patients suffering from central cyanosis with SPO2< 90% (for asthmatic patients with SPO2<88%)
  • Pregnant or lactating women
  • Patients with a known history of pro-inflammatory diseases (patients with autoimmune diseases, patients receiving chemotherapy for cancer, patients with malabsorption, patients with inflammatory bowel disease, Crohn's disease or ulcerative colitis).
  • History or suspected immunosuppressive or immunodeficient state including HIV infection, or chronic immunosuppressant medication (more than 14 days) within the past 3 months (inhaled and topical steroids are allowed).
  • Patients with severe renal impairment (GFR <60 ml/min/1.73m2 as measured by the Cockcroft-Gault formula).
  • Patient with severe hepatic impairment, biliary cirrhosis or cholestasis
  • Patients who received immunoregulatory therapy within one month before the start of the study.
  • Patients with Known or suspected allergy or any contraindications to Lactoferrin.
  • Any condition, according to the judgment of the investigator, would interfere with the patient's ability to comply with all study requirements or that would place the patient at unacceptable risk by his/her participation in the study.

Sites / Locations

  • National Research Center, Egypt (Clinical and Molecular Pharmacology)
  • Clinmax CRO (Clinical Research Organization)
  • Clinical Trial Unit National Research Center
  • Egyptian Military Medical Services (Hospitals)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm 01 (SOC + Lactoferrin 1200 mg QID)

Arm 02 (SOC + Placebo QID)

Arm Description

Patients randomized to this group will receive two 600 mg Lactoferrin tablets QID plus the Standard of Care (SOC) treatment(s).

Patients randomized to this group will receive two placebo tablets QID plus the SOC treatment(s).

Outcomes

Primary Outcome Measures

Survival rate.
Comparing the influence of the intervention on the Survival rate.
Rate of disease remission.
For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT - For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.
The number of patients with PCR negative results.
Comparing the influence of the intervention on the PCR negative results.

Secondary Outcome Measures

Mean change in the disease severity (clinical assessment).
Recording the changes from severe to moderate or mild and the time taken.
Mean change in blood pressure.
Recording the changes in blood pressure mmHg.
Mean change in heart beats.
Recording the changes in heart rate in beat/second.
Mean change in body temperature.
Recording the changes in body temperature in Celsius.
Mean change in body respiratory rate.
Recording the changes in the respiratory rate in breath/minute.
Mean change in oxygen saturation.
Recording the changes in arterial oxygen saturation in mmHg.
Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
Mean change in complete blood picture (CBC).
Recording the changes in complete blood picture (CBC) in cells per liter.
Mean change in C reactive protein (CRP).
Recording the changes in C reactive protein (CRP) in mg/L.
Mean change in erythrocyte sedimentation rate (ESR).
Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.
Mean change in D-dimer.
Recording the changes in D-dimer in ng/mL.
Mean change in ferritin.
Recording the changes in ferritin in ng/mL.
Mean change in liver Albumin.
Recording the changes in liver Albumin in g/L.
Mean change in total and direct Bilirubin.
Recording the changes in total and direct Bilirubin in mg/dL.
Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).
Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).
Mean change in aspartate aminotransferase (AST).
Recording the changes in aspartate aminotransferase (AST) in IU/L.
Mean change in Alanine Aminotransferase (ALT).
Recording the changes in Alanine Aminotransferase (ALT) in IU/L.
Mean change in Blood Urea Nitrogen (BUN).
Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.
Mean change in Serum Creatinine.
Recording the changes in Serum Creatinine in mg/dL.
Mean change in Serum Creatinine clearance.
Recording the changes in Serum Creatinine in ml/min.
Mean change in Glomerular filtration rate (GFR ).
Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.
The mean change in serum interleukin-1 (IL-1).
Recording the changes in interleukin-1 (IL-1) in pg/ml.
The mean change in serum interleukin-6 (IL-6).
Recording the changes in interleukin-6 (IL-6) in pg/ml.
The mean change in serum interleukin-10 (IL-10).
Recording the changes in interleukin-10 (IL-10) in pg/ml.
The mean change in serum tumor necrosis factor-alpha (TNF alpha).
Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.
Mean changes in immunoglobulin G (IgG).
Recording the changes in immunoglobulin G (IgG) in ng/ml.
Mean changes in immunoglobulin M (IgM).
Recording the changes in immunoglobulin M (IgM) in ng/ml.
The mean change in PCR viral load.
Recording the changes in PCR viral load in copies/mL.
Mean change in lung CT manifestation.
Recording the changes in lung CT.
Nature and severity of Adverse Events.
Recording any unexpected Adverse Events of the intervention.
Time for lung recovery.
Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.
The number of missed drug doses among each treatment group.
Recording the changes the event of missed drug doses.

Full Information

First Posted
May 15, 2020
Last Updated
November 12, 2021
Sponsor
National Research Centre, Egypt
Collaborators
Egyptian Military Medical Services
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1. Study Identification

Unique Protocol Identification Number
NCT04412395
Brief Title
Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease
Acronym
COVID-19_LF
Official Title
Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 1, 2022 (Anticipated)
Primary Completion Date
August 1, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Research Centre, Egypt
Collaborators
Egyptian Military Medical Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19 patients. The study was approved by the ethical committee of the Egyptian Center for Research and Regenerative Medicine in 11-5-2020.
Detailed Description
The World Health Organization (WHO) declared the coronavirus (SARS-CoV-2, COVID-19) outbreak a Public Health Emergency of International Concern with a pandemic spread. The situation is rapidly evolving, which raises the approach of reproposing already approved drugs to meet the emerging challenge and to save time and money. Lactoferrin (Lf) is a natural glycoprotein that broadly distributed within the body fluids and found predominantly in milk. It represents a known component of the innate immune system. The antiviral activity of Lf has been reported against many viruses, including SARS-CoV-1, through blocking the viral receptors on the host cells preventing them from entry and replication. Markedly, data reveals that Lf interacts with Heparan Sulfate Proteoglycans (HSPGs) and Angiotensin Converting Enzyme 2 (ACE2) receptors that are reported as SARS-CoV-2-binding sites to enter the host cell, suggesting a potential significance of Lf as an antiviral against SARS-CoV-2. Moreover, the immunoregulatory effects of Lf can protect against the cytokine-storm and thrombotic complications that result from the COVID-19-induced over-stimulated inflammatory response and exaggerated immune reactions. In addition, Lf can decrease the free iron toxicity caused by the virus as it has a strong iron chelating ability. Lf is a safe approved food supplement that is available in the markets for enhancement of immunity and for treatment of anemia. The aim of this study is to perform a randomized, double-blind, placebo-controlled, two arms, clinical trial to assess oral enteric-coated tablet of bovine apolactoferrin (the low iron-content form of Lf) as a safe antiviral and immunoregulatory therapy in patients diagnosed with COVID-19 disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome, Coronavirus Infection, COVID-19, SARS-CoV 2
Keywords
Lactoferrin, Apolactoferrin, Immuno-modulatory, Cytokine-storm, Antiviral, 2019nCoV, 2019 new coronavirus (2019nCoV), Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome (ARDS), COVID-19, SARS-CoV 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled, clinical trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
516 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 01 (SOC + Lactoferrin 1200 mg QID)
Arm Type
Active Comparator
Arm Description
Patients randomized to this group will receive two 600 mg Lactoferrin tablets QID plus the Standard of Care (SOC) treatment(s).
Arm Title
Arm 02 (SOC + Placebo QID)
Arm Type
Placebo Comparator
Arm Description
Patients randomized to this group will receive two placebo tablets QID plus the SOC treatment(s).
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactoferrin (Apolactoferrin)
Intervention Description
Apolactoferrin is an iron-free Lactoferrin (with very low iron saturation). Lactoferrin (Lf) is a natural glycoprotein that is found predominantly in milk. Lf represents a known component of the innate immune system present in neutrophil-specific granules and broadly distributed within the body fluids and exocrine secretions.
Intervention Type
Drug
Intervention Name(s)
Placebo of excipient(s) will be administered
Other Intervention Name(s)
excipient(s)
Intervention Description
Placebo of the equivalent excipient will be administered to placebo group
Primary Outcome Measure Information:
Title
Survival rate.
Description
Comparing the influence of the intervention on the Survival rate.
Time Frame
up to 8 weeks.
Title
Rate of disease remission.
Description
For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT - For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.
Time Frame
up to 4 weeks.
Title
The number of patients with PCR negative results.
Description
Comparing the influence of the intervention on the PCR negative results.
Time Frame
up to 4 weeks.
Secondary Outcome Measure Information:
Title
Mean change in the disease severity (clinical assessment).
Description
Recording the changes from severe to moderate or mild and the time taken.
Time Frame
up to 4 weeks.
Title
Mean change in blood pressure.
Description
Recording the changes in blood pressure mmHg.
Time Frame
up to 4 weeks.
Title
Mean change in heart beats.
Description
Recording the changes in heart rate in beat/second.
Time Frame
up to 4 weeks.
Title
Mean change in body temperature.
Description
Recording the changes in body temperature in Celsius.
Time Frame
up to 4 weeks.
Title
Mean change in body respiratory rate.
Description
Recording the changes in the respiratory rate in breath/minute.
Time Frame
up to 4 weeks.
Title
Mean change in oxygen saturation.
Description
Recording the changes in arterial oxygen saturation in mmHg.
Time Frame
up to 4 weeks.
Title
Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
Description
Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
Time Frame
up to 4 weeks.
Title
Mean change in complete blood picture (CBC).
Description
Recording the changes in complete blood picture (CBC) in cells per liter.
Time Frame
up to 4 weeks.
Title
Mean change in C reactive protein (CRP).
Description
Recording the changes in C reactive protein (CRP) in mg/L.
Time Frame
up to 4 weeks.
Title
Mean change in erythrocyte sedimentation rate (ESR).
Description
Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.
Time Frame
up to 4 weeks.
Title
Mean change in D-dimer.
Description
Recording the changes in D-dimer in ng/mL.
Time Frame
up to 4 weeks.
Title
Mean change in ferritin.
Description
Recording the changes in ferritin in ng/mL.
Time Frame
up to 4 weeks.
Title
Mean change in liver Albumin.
Description
Recording the changes in liver Albumin in g/L.
Time Frame
up to 4 weeks.
Title
Mean change in total and direct Bilirubin.
Description
Recording the changes in total and direct Bilirubin in mg/dL.
Time Frame
up to 4 weeks.
Title
Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).
Description
Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).
Time Frame
up to 4 weeks.
Title
Mean change in aspartate aminotransferase (AST).
Description
Recording the changes in aspartate aminotransferase (AST) in IU/L.
Time Frame
up to 4 weeks.
Title
Mean change in Alanine Aminotransferase (ALT).
Description
Recording the changes in Alanine Aminotransferase (ALT) in IU/L.
Time Frame
up to 4 weeks.
Title
Mean change in Blood Urea Nitrogen (BUN).
Description
Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.
Time Frame
up to 4 weeks.
Title
Mean change in Serum Creatinine.
Description
Recording the changes in Serum Creatinine in mg/dL.
Time Frame
up to 4 weeks.
Title
Mean change in Serum Creatinine clearance.
Description
Recording the changes in Serum Creatinine in ml/min.
Time Frame
up to 4 weeks.
Title
Mean change in Glomerular filtration rate (GFR ).
Description
Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.
Time Frame
up to 4 weeks.
Title
The mean change in serum interleukin-1 (IL-1).
Description
Recording the changes in interleukin-1 (IL-1) in pg/ml.
Time Frame
up to 4 weeks.
Title
The mean change in serum interleukin-6 (IL-6).
Description
Recording the changes in interleukin-6 (IL-6) in pg/ml.
Time Frame
up to 4 weeks.
Title
The mean change in serum interleukin-10 (IL-10).
Description
Recording the changes in interleukin-10 (IL-10) in pg/ml.
Time Frame
up to 4 weeks.
Title
The mean change in serum tumor necrosis factor-alpha (TNF alpha).
Description
Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.
Time Frame
up to 4 weeks.
Title
Mean changes in immunoglobulin G (IgG).
Description
Recording the changes in immunoglobulin G (IgG) in ng/ml.
Time Frame
up to 4 weeks.
Title
Mean changes in immunoglobulin M (IgM).
Description
Recording the changes in immunoglobulin M (IgM) in ng/ml.
Time Frame
up to 4 weeks.
Title
The mean change in PCR viral load.
Description
Recording the changes in PCR viral load in copies/mL.
Time Frame
up to 4 weeks.
Title
Mean change in lung CT manifestation.
Description
Recording the changes in lung CT.
Time Frame
up to 4 weeks.
Title
Nature and severity of Adverse Events.
Description
Recording any unexpected Adverse Events of the intervention.
Time Frame
up to 4 weeks.
Title
Time for lung recovery.
Description
Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.
Time Frame
up to 8 weeks.
Title
The number of missed drug doses among each treatment group.
Description
Recording the changes the event of missed drug doses.
Time Frame
up to 4 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients tested positive (PCR) for SARS-CoV-2 and clinically symptomatic. Adult patients with age >18 years. Patients willing and able to sign the study informed consent form. Exclusion Criteria: Critically severe disease patients (having Respiratory failure requiring mechanical ventilation, or signs of septic shock or multiple organ failure requiring ICU admission). Patients who are unconscious Patients who have convulsions Patients suffering from central cyanosis with SPO2< 90% (for asthmatic patients with SPO2<88%) Pregnant or lactating women Patients with a known history of pro-inflammatory diseases (patients with autoimmune diseases, patients receiving chemotherapy for cancer, patients with malabsorption, patients with inflammatory bowel disease, Crohn's disease or ulcerative colitis). History or suspected immunosuppressive or immunodeficient state including HIV infection, or chronic immunosuppressant medication (more than 14 days) within the past 3 months (inhaled and topical steroids are allowed). Patients with severe renal impairment (GFR <60 ml/min/1.73m2 as measured by the Cockcroft-Gault formula). Patient with severe hepatic impairment, biliary cirrhosis or cholestasis Patients who received immunoregulatory therapy within one month before the start of the study. Patients with Known or suspected allergy or any contraindications to Lactoferrin. Any condition, according to the judgment of the investigator, would interfere with the patient's ability to comply with all study requirements or that would place the patient at unacceptable risk by his/her participation in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rehab Hegazy, PhD
Phone
+201001507676
Email
rehab_hegazy@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Osama Azmy, MD
Phone
+201223103084
Email
osamaazmy@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rehab Hegazy, PhD
Organizational Affiliation
National Research Center
Official's Role
Study Director
Facility Information:
Facility Name
National Research Center, Egypt (Clinical and Molecular Pharmacology)
City
Cairo
State/Province
Giza
ZIP/Postal Code
12622
Country
Egypt
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marawan Abdelbaset, PhD
Phone
+0201002227202
Email
dr.marawan@gmail.com
First Name & Middle Initial & Last Name & Degree
Bassim Mohamed, PhD
Email
Bassim.mohamed@umontreal.ca
First Name & Middle Initial & Last Name & Degree
Marawan Abdelbaset, PhD
First Name & Middle Initial & Last Name & Degree
Bassim Mohamed, PhD
Facility Name
Clinmax CRO (Clinical Research Organization)
City
Cairo
ZIP/Postal Code
11835
Country
Egypt
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Khaled Prince, B Pharm
Phone
+20106725802
Email
Khaled.prince@clinmax.net
First Name & Middle Initial & Last Name & Degree
Christine Gindy, B Pharm
Email
christine.gindy@clinmax.net
Facility Name
Clinical Trial Unit National Research Center
City
Cairo
Country
Egypt
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wafaa Abdel Aal, MD
First Name & Middle Initial & Last Name & Degree
Osama Azmy, MD
Facility Name
Egyptian Military Medical Services (Hospitals)
City
Cairo
Country
Egypt

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Not yet decided.
IPD Sharing Time Frame
within 6 month
IPD Sharing Access Criteria
all valid data

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Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease

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