IFN-beta 1b and Remdesivir for COVID19

December 9, 2020 updated by: The University of Hong Kong

An Open-label Randomized Controlled Trial on Interferon β-1b and Remdesivir Combination Versus Remdesivir as Treatment for COVID-19 Infection

A 5-day combination of interferon β-1b and remdesivir will expedite the recovery, suppress the viral load and shorten hospitalisation in patients with SARS-CoV-2 infection compare to the control arm

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Introduction The novel coronavirus (SARS-CoV-2), is a single-stranded RNA coronavirus. The virus was first isolated from patients presented with pneumonia in Wuhan in December 2019. It is believed that the virus first emerged from patients working in the Wuhan Seafood Market which also sold contaminated wild animals, consumed as a local delicacy. Sequences of the Wuhan betacoronavirus show similarities to betacoronaviruses found in bats, sharing a common ancestor with the 2003 SARS coronavirus (SARS-CoV) and the bat coronavirus HKU, a virus found in fruit bats. Similar to SARS-CoV, it is a member of Beta-CoV lineage B. Five genomes of the novel coronavirus have been initially isolated and reported including BetaCoV/Wuhan/IVDC-HB-01/2019, BetaCoV/Wuhan/IVDC-HB-04/2020, BetaCoV/Wuhan/IVDC-HB-05/2019, BetaCoV/Wuhan/WIV04/2019, and BetaCoV/Wuhan/IPBCAMS-WH-01/2019 from the China CDC.

The SARS-CoV-2 has since spread from China to the rest of the world. As of 20 November 2020, more than 50 million people been confirmed to have infected by SARS-CoV-2, resulting in more than 1,000,000 deaths. Remdesivir has been shown to clinically effective in severe Covid-19 patients but virological data is lacking. FDA has approved the use of remdesivir for the treatment of severe Covid-19 infection. Apart from remdesivir, no specific antiviral treatment for the SARS-CoV-2 is currently available, but existing medication could be repurposed.

Genetic sequencing demonstrated similarity of the SARS-CoV-2 to the SARS-CoV and MERS CoV. We expect patients infected with the SARS-CoV-2 will also present similarly with initial upper respiratory tract symptoms including fever, cough, sputum, myalgia and shortness or breath. More severe cases might complicate with pneumonia and required ventilatory or ECMO support. According to our previous studies in 2003 on patients hospitalized for severe SARS-CoV, the viral load peaked between day 7 from symptoms onset and coincided with clinical deterioration of pneumonia and respiratory failure, with majority of the patients required intensive care support. Higher viral load isolated from different human system also correlated with worsened SARS manifestation and complications.

Previously, the investigators have demonstrated that interferon-beta1b, commonly used in the treatment of multiple sclerosis and lopinavir/ ritonavir, also demonstrated to improve the outcome of MERS-CoV infection in a non-human primate model of common marmoset. A more recent open-label, randomized controlled trial by our team has proven that interferon beta-1b, in combination with lopinavir/ ritonavir and ribavirin reduced the SARS-CoV-2 viral load in the respiratory tract and resulted in faster alleviation of clinical symptoms when compared to lopinavir/ ritonavir alone or with ribavirin, suggesting that interferon beta-1b was likely to be the backbone of this triple therapy.

Therefore, the investigators propose to conduct an open-label randomized controlled trial on interferon beta-1b and remdesivir combination versus remdesivir as treatment for patients hospitalized for COVID-19 infection

Patients will be randomly assigned to one of the two groups: Group A: a 5-day course of subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5, or Group B: a 5-day course of IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5 (1:1).

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Kelvin KW To, MD FRCPath
  • Phone Number: 22553111
  • Email: kelvinto@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong, 852
        • Recruiting
        • Queen Mary Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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. Recruited subjects include all adult patients ≥18 years hospitalized for virologic confirmed SARS-CoV-2 infection.
  2. Fulfilling one of the following criteria associated with high risk of clinical deterioration: age 65 years or above, radiological evidence of pneumonia, oxygen desaturation <94% on room air, comorbidity including hypertension, diabetes, cardiovascular diseases, chronic obstructive lung disease, chronic liver diseases, chronic kidney diseases, malignancy, haematological diseases, rheumatological diseases, immunocompromised hosts and obesity (BMI > 30)
  3. All subjects give written informed consent. For patients who are critically ill, requiring ICU, ventilation or confused, informed consent will be obtained from spouse, next-of-kin or legal guardians.
  4. Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.

Exclusion Criteria:

  1. Inability to comprehend and to follow all required study procedures.
  2. Allergy or severe reactions to the study drugs
  3. Patients taking medication that will potentially interact with l interferon beta-1b and remdesivir
  4. Patients with known history of severe depression
  5. Estimated glomerular filtration rate <30 mL/min
  6. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study.
  7. To participate in an unrelated trial during the current clinical trial. Nevertheless, the patients have the right to withdraw from the current clinical trial to join another clinical trial.
  8. Have a history of alcohol or drug abuse in the last 5 years.
  9. Have any condition that the investigator believes may interfere with successful completion of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IFN-beta 1b and remdesivir
a 5-day course of subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5
Drug: Interferon beta-1b
a 5-day course of subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5
Other Names:
  • Remdesivir
Active Comparator: Remdesivir
a 5-day course of IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5
Drug: Remdesivir
a 5-day course of IV remdesivir 200mg loading on day 1 followed by remdesivir 100mg daily on day 2 to day 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical improvement
Time Frame: 30 days
Time to complete alleviation of symptoms as defined by NEWS of 0 maintained for 24 hours
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 30 days
30-day mortality
30 days
Hospitalisation
Time Frame: 30 days
Length of hospitalization
30 days
NPS viral load
Time Frame: 7 days
Time to negative nasopharyngeal swab (NPS) SARS-CoV-2 RT-PCR
7 days
TS viral load
Time Frame: 7 days
Time to negative throat saliva (TS) SARS-CoV-2 RT-PCR
7 days
Inflammatory markers
Time Frame: 7 days
Cytokine/ chemokine changes
7 days
Adverse events
Time Frame: 5 days
Adverse events during treatment
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 20, 2020

Primary Completion (Anticipated)

July 31, 2021

Study Completion (Anticipated)

September 30, 2021

Study Registration Dates

First Submitted

November 27, 2020

First Submitted That Met QC Criteria

November 27, 2020

First Posted (Actual)

December 1, 2020

Study Record Updates

Last Update Posted (Actual)

December 10, 2020

Last Update Submitted That Met QC Criteria

December 9, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 20-535

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Anonymous IPD will be shared upon request to the HKU IRB and approved by the panel

IPD Sharing Time Frame

Upon study publication for 12 months

IPD Sharing Access Criteria

Approval by the IRB panel

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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