Efficacy and Safety of Liposomal Lactoferrin in COVID-19 Patients With Mild-to-Moderate Disease and in COVID-19 Asymptomatic Patients

NCT04475120 | Completed Phase 2

• 1 other identifier: 4220
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 is considered an ongoing international global health problem which already caused 12 million confirmed cases. No specific effective treatment has been identified so far, and available supportive therapies are intended just to severe patients. Asymptomatic and mildly symptomatic patients remain a transmission reservoir, with possible evolution to the most severe disease form, without a clear treatment indication. Lactoferrin (Lf) is a multifunctional glycoprotein, belonging to transferrin family, secreted by exocrine glands and neutrophils and present in all human secretion. The pleiotropic activity of Lf is mainly based on its four different functions: chelate two ferric iron per molecule, interact with anionic molecules, enter inside nucleus and modulate iron homeostasis. The ability to chelate two ferric ions per molecule is associated to the inhibition of reactive oxygen species formation as well as this sequestration of iron, pivotal for bacterial and viral replication, is at the basis of its antibacterial and antiviral activity. Moreover, Lf exerts its antiviral activity against the majority of the tested viruses by binding to heparan sulphate, while against few viruses by interacting with surface components of viral particles. The capability of Lf to exert antiviral activity, by binding to host cells or viral particles or both, strengthens the idea that this glycoprotein is "an important brick in the mucosal wall, effective against viral attacks". Lf was able to block the binding of the spike protein to host cells, indicating that Lf exerted its inhibitory function at the viral attachment stage. The current accepted model suggests that Lf could block viral entry by interacting with heparan sulfate proteoglycans (HSPGs), which mediate the transport of extracellular virus particles from the low affinity anchoring sites to the high affinity specific entry as ACE-2. Investigators performed a prospective, interventional pilot study to assess the efficacy of liposomal lactoferrin in COVID-19 patients with mild-to moderate disease and in COVID-19 asymptomatic patients. Secondary objectives evaluated the safety and tolerability of liposomal lactoferrin for oral and intra-nasal use.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Rate of viral clearance Time to viral clearance

  time to naso-oro-pharingeal swab negativization

  30 days

Secondary Outcomes (1)

• Time to clinical improvement

  30 days

Study Arms (4)

Liposomal Lacroferrin

EXPERIMENTAL

Thirty-two patients (14 hospitalised and 18 in home-based isolation) belonging to the first group received oral and intranasal liposomal bLf. BLf capsules for oral use containing 100 mg of bLf encapsulated in liposome while bLf nasal spray had about 8 mg/ml of bLf encapsulated in liposome. BLf, contained in both products, was tested by SDS-PAGE and silver nitrate staining and its purity was about 95%. The bLf iron saturation was about 5% as detected via optical spectroscopy at 468 nm based on an extinction coefficient of 0.54 (100% iron saturation, 1% solution). The scheduled dose treatment of liposomal bLf for oral use was 1gr per day for 30 days (10 capsules per day) in addition to the same formulation intranasally administered 3 times daily (a total of about 16 mg/nostril)

Drug: liposomal lactoferrin

SOC therapy

ACTIVE COMPARATOR

Thirty-two hospitalized patients belonging to the second group were only treated with SOC regimen according to the national guidelines at the time of the enrollment: lopinavir/ritonavir cps 200/50 mg, 2x2/day (alternatively darunavir 800 mg 1 cp/day+ritonavir 100 mg 1 cp/day or darunavir/cobicistat 800/150 mg 1 cp/day), chloroquine 500 mg, 1x2/day or hydroxychloroquine cp 200 mg, 1x2/day. SOC regimen lasted from 5 to 20 days, with timing to be established according to clinical course.

Drug: SOC therapy

Home-based isolation

NO INTERVENTION

Twenty-eight patients, in home-based isolation, belonging to the third group did not receive any therapy.

Healthy volunteers

NO INTERVENTION

A control group, comprising 32 healthy volunteers, did not receive any treatment or placebo.

Interventions

liposomal lactoferrin DRUG

oral and intra-nasal formulation

Liposomal Lacroferrin

SOC therapy DRUG

oral administration

SOC therapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients were over 20years old, with a confirmed positivity to COVID-19 at the oropharyngeal swab

You may not qualify if:

• pregnant and lactating women, patients taking nitric oxide and nitrates, patients with reported allergy to milk proteins, patients with a previous history of bronchial hyperactivity and patients with pre-existing respiratory diseases. COVID-19 patients requiring intensive care or mechanical ventilation were excluded.

Sponsors & Collaborators

• University of Rome Tor Vergata: lead

Study Sites (1)

University of Rome Tor Vergata

Rome, 00133, Italy

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 17, 2020
• Study Start: April 15, 2020
• Primary Completion: July 2, 2020
• Study Completion: July 2, 2020
• Last Updated: May 14, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (1)