Clinical Study for the Treatment With Interferon-ß-1a (IFNß-1a) of COVID-19 Patients (INTERCOP)

Randomized, Controlled, Open Label, Phase 2 Clinical Trial of Interferon-β-1a (IFNβ-1a) in COVID-19 Patients

Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking.

Since two clinical stages of COVID-19 are emerging, an early one with typical clinical characteristics of a viral infection (fever, malaise, cough) and a later one with pneumonia leading to progressive respiratory failure, associated with heavy, cytokine-mediated, inflammation, an intervention by a compound possessing both antiviral activity and immunomodulatory effects would be most effective at the earliest possible stage.

The purpose of this clinical trial is to test the efficacy of Interferon-β-1a (IFNβ-1a), in COVID-19 patients in an open label, randomized clinical trial.

The design of the study is to test IFNβ-1a in addition to standard of care compared with standard of care alone.

The primary outcome is the time to negative conversion of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) nasopharyngeal swabs.

Study Overview

• Status: Terminated
• Conditions: COVID-19 Virus Infection
• Intervention / Treatment: Drug: Interferon-ß-1a; Combination product: Standard of Care (SOC)

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent signed
2. Patients hospitalized with confirmed swab RT-PCR detection of SARS-CoV-2
3. X-ray and/or CT diagnosed pneumonia
4. Age >=18 years
5. Clinical status defined as 3, 4 or 5 on the 7-point ordinal scale

Exclusion Criteria:

1. Known allergy or hypersensitivity to IFNß-1a or IFNß-1b
2. Presence of severe concomitant illnesses/medical conditions that in the physician opinion do not allow participation to the study
3. Pregnant or lactating females
4. History of major depression disorder or suicidal attempt or suicidal ideation
5. Spontaneous blood alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels > 5 times the upper limit of normal
6. Clinical status defined as 1, 2, or 6 on the 7-point ordinal scale

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard care	Combination product: Standard of Care (SOC); Any pharmacological (e.g. antibiotics, etc.) and non-pharmacological (e.g. oxygen, ventilation, etc.) treatments prescribed on clinical grounds; Other Names: SOC
EXPERIMENTAL: IFNβ 1a	Drug: Interferon-ß-1a; IFNβ-1a will be administered subcutaneously at a dose of 44 mcg (equivalent to 12 million international units), three times per week at least 48 hours apart, for a total of two weeks. All patients will receive a total dose of 264 mcg (72 million international units) under physician control; Other Names: IFNß-1a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to negative conversion of SARS-CoV-2 nasopharyngeal swab	Viral load will be measured by Real Time-Polymerase Chain Reaction (RT-PCR)	From baseline to day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in clinical severity score (a)	Defined as percentage of patients reporting each severity rating on a 7-point ordinal scale	Baseline, days 7, 15, 21, 29
Improvement in clinical severity score (b)	Defined as the time to clinical improvement of two points from the time of randomization on a 7-category ordinal scale or live discharge from the hospital, whichever comes first	Baseline, days 7, 15, 21, 29
Incidence of new oxygen use, non-invasive ventilation, or high flow oxygen devices during the trial		From baseline to day 29
Oxygenation free days in the first 28 days		From baseline to day 29
Ventilator free days in the first 28 days		From baseline to day 29
Incidence of new mechanical ventilation use during the trial		From baseline to day 29
Number of patients transferred to Intensive Care Unit (ICU)		From baseline to day 29
Mortality rate		From baseline to day 29
Changes from baseline in pulmonary computed tomography (CT) imaging severity score	Measured with artificial intelligence and expressed as cc and percent values of diseased lung (lung consolidation, ground glass opacities and disease free)	Baseline, day 21; extra follow up at 90 days
Duration of hospital stay expressed in days		From baseline to day 29
Viral load measured on plasma with RT-PCR		Baseline, days 3, 5, 7, 9, 11, 13, 15, 21, 29

Other Outcome Measures

Outcome Measure	Time Frame
Plasma and peripheral blood mononuclear cell messenger-RNA (mRNA) expression profile of interferon stimulated genes (ISG)	Baseline, day 15
Antibodies to SARS-CoV-2	Baseline, days 7, 15, 29
Antibodies to IFN-β1a	Baseline, days 7, 15, 29

Collaborators and Investigators

• Sponsor: Emanuele Bosi
• Investigators: Principal Investigator: Emanuele Bosi, Professor, IRCCS Ospedale San Raffaele

Publications and helpful links

General Publications

• Bosi E, Bosi C, Rovere Querini P, Mancini N, Calori G, Ruggeri A, Canzonieri C, Callegaro L, Clementi M, De Cobelli F, Filippi M, Bregni M. Interferon beta-1a (IFNbeta-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. Trials. 2020 Nov 23;21(1):939. doi: 10.1186/s13063-020-04864-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 2, 2020
• Primary Completion (ACTUAL): March 30, 2021
• Study Completion (ACTUAL): March 30, 2021

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (ACTUAL): June 26, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons
• Other Study ID Numbers: INTERCOP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No