The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant fortreatment and to assess the potential in reducing mortality and morbidity rates inCOVID-19 patients. The study was approved by the ethical committee of the Egyptian Centerfor Research and Regenerative Medicine in 11-5-2020.
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.
Dietary Supplement: Lactoferrin (Apolactoferrin)
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.
Drug: Placebo of excipient(s) will be administered
Placebo of the equivalent excipient will be administered to placebo group
Other Name: excipient(s)
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.
National Research Center, Egypt (Clinical and Molecular Pharmacology)
Cairo, Giza, Egypt
Clinmax CRO (Clinical Research Organization)
Cairo, Egypt
Clinical Trial Unit National Research Center
Cairo, Egypt
Egyptian Military Medical Services (Hospitals)
Cairo, Egypt
Rehab Hegazy, PhD
+201001507676
rehab_hegazy@hotmail.com
Osama Azmy, MD
+201223103084
osamaazmy@yahoo.com
Rehab Hegazy, PhD, Study Director
National Research Center