Clinical trial NCT04412395: Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease
Official title: Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: 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
Lead sponsor: National Research Centre, Egypt
Sponsor class: OTHER
Collaborators: name: Egyptian Military Medical Services
First posted: 2020-06-02
Enrollment: 516
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, clinical trial.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Survival rate.
timeFrame: up to 8 weeks.
measure: Rate of disease remission.
timeFrame: up to 4 weeks.
measure: The number of patients with PCR negative results.
timeFrame: up to 4 weeks.
Secondary outcomes:
measure: Mean change in the disease severity (clinical assessment).
timeFrame: up to 4 weeks.
measure: Mean change in blood pressure.
timeFrame: up to 4 weeks.
measure: Mean change in heart beats.
timeFrame: up to 4 weeks.
measure: Mean change in body temperature.
timeFrame: up to 4 weeks.
measure: Mean change in body respiratory rate.
timeFrame: up to 4 weeks.
measure: Mean change in oxygen saturation.
timeFrame: up to 4 weeks.
measure: Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
timeFrame: up to 4 weeks.
measure: Mean change in complete blood picture (CBC).
timeFrame: up to 4 weeks.
measure: Mean change in C reactive protein (CRP).
timeFrame: up to 4 weeks.
measure: Mean change in erythrocyte sedimentation rate (ESR).
timeFrame: up to 4 weeks.
measure: Mean change in D-dimer.
timeFrame: up to 4 weeks.
measure: Mean change in ferritin.
timeFrame: up to 4 weeks.
measure: Mean change in liver Albumin.
timeFrame: up to 4 weeks.
measure: Mean change in total and direct Bilirubin.
timeFrame: up to 4 weeks.
measure: Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).
timeFrame: up to 4 weeks.
measure: Mean change in aspartate aminotransferase (AST).
timeFrame: up to 4 weeks.
measure: Mean change in Alanine Aminotransferase (ALT).
timeFrame: up to 4 weeks.
measure: Mean change in Blood Urea Nitrogen (BUN).
timeFrame: up to 4 weeks.
measure: Mean change in Serum Creatinine.
timeFrame: up to 4 weeks.
measure: Mean change in Serum Creatinine clearance.
timeFrame: up to 4 weeks.
measure: Mean change in Glomerular filtration rate (GFR ).
timeFrame: up to 4 weeks.
measure: The mean change in serum interleukin-1 (IL-1).
timeFrame: up to 4 weeks.
measure: The mean change in serum interleukin-6 (IL-6).
timeFrame: up to 4 weeks.
measure: The mean change in serum interleukin-10 (IL-10).
timeFrame: up to 4 weeks.
measure: The mean change in serum tumor necrosis factor-alpha (TNF alpha).
timeFrame: up to 4 weeks.
measure: Mean changes in immunoglobulin G (IgG).
timeFrame: up to 4 weeks.
measure: Mean changes in immunoglobulin M (IgM).
timeFrame: up to 4 weeks.
measure: The mean change in PCR viral load.
timeFrame: up to 4 weeks.
measure: Mean change in lung CT manifestation.
timeFrame: up to 4 weeks.
measure: Nature and severity of Adverse Events.
timeFrame: up to 4 weeks.
measure: Time for lung recovery.
timeFrame: up to 8 weeks.
measure: The number of missed drug doses among each treatment group.
timeFrame: up to 4 weeks.
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Research Center, Egypt (Clinical and Molecular Pharmacology)
state: Giza
city: Cairo
country: Egypt
facility: Clinmax CRO (Clinical Research Organization)
city: Cairo
country: Egypt
facility: Clinical Trial Unit National Research Center
city: Cairo
country: Egypt
facility: Egyptian Military Medical Services (Hospitals)
Study officials:
affiliation: National Research Center
name: Rehab Hegazy, PhD
role: STUDY_DIRECTOR
References: