IFN Beta-1b and Ribavirin for Covid-19

Sponsor

The University of Hong Kong (Other)

Overall Status

Unknown status

CT.gov ID

NCT04494399

Collaborator

Hospital Authority, Hong Kong (Other)

Enrollment

Location

Arms

24.1

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

As of 1 July 2020, more than 10 million people been confirmed to have infected by SARS-CoV-2, resulting in more than 500,000 deaths. No specific antiviral treatment for the SARS-CoV-2 is currently available, but existing medication could be repurposed.

The investigators therefore propose to conduct an open-label randomized controlled trial on a short course of interferon β-1b and ribavirin combination treatment for patients hospitalized for COVID-19 infection.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: Interferon beta-1b Drug: Ribavirin	Phase 2

Detailed Description

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).

The SARS-CoV-2 has since spread from China to the rest of the world. As of 1 July 2020, more than 10 million people been confirmed to have infected by SARS-CoV-2, resulting in more than 500,000 deaths. No specific antiviral treatment for the SARS-CoV-2 is currently available, but existing medication could be repurposed.

Previously, the investigators have demonstrated that interferon beta-1b, 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. More recently, the investigators have demonstrated that the triple combination of interferon β-1b, lopinavir/ ritonavir and ribavirin was significantly more effective in alleviating symptoms and respiratory SARS-CoV-2 viral load than lopinavir/ ritonavir with ribavirin or lopinavir/ ritonavir alone, suggesting that interferon β-1b might be the most potent antiviral among the three and lopinavir/ ritonavir is associated with relatively more side effects including diarrhoea and cardiac arrhythmia.

Therefore, the investigators propose to conduct an open-label randomized controlled trial on a short course of interferon β-1b and ribavirin combination treatment for patients hospitalized for COVID-19 infection.

Patients will be randomly assigned to one of the two groups: the Treatment group: a 5-day course of subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and oral ribavirin 400mg twice daily, or the Control group: supportive care alone (1:1).

For patients randomized to the Control group, if the nasopharyngeal swab (NPS) or throat saliva (TS) viral load is still detectable on day 3, the patients will receive the same treatment as in the Treatment group from day 4 to day 8.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

open label randomised controlled trialopen label randomised controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Randomised Controlled Trial on IFN Beta-1b and Ribavirin Combination, as Treatment for Covid-19 Infection

Actual Study Start Date :

Jul 29, 2020

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment group 5-day course of daily subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and oral ribavirin 400mg twice daily plus standard care	Drug: Interferon beta-1b 5-day course of daily subcutaneous injection of interferon β-1b 16 million IU Drug: Ribavirin 5-day course of oral ribavirin 400mg twice daily
No Intervention: Control group Standard care alone

Arm

Intervention/Treatment

Active Comparator: Treatment group

5-day course of daily subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and oral ribavirin 400mg twice daily plus standard care

Drug: Interferon beta-1b

5-day course of daily subcutaneous injection of interferon β-1b 16 million IU

Drug: Ribavirin

5-day course of oral ribavirin 400mg twice daily

No Intervention: Control group

Standard care alone

Outcome Measures

Primary Outcome Measures

Clinical symptoms alleviation [7 days]
Time to complete alleviation of symptoms as defined by NEWS2 of 0 maintained for 24 hours

Secondary Outcome Measures

Hospitalisation [14 days]
Length of hospitalisation
Time to negative viral load [7 days]
Time to negative nasopharyngeal swab and throat saliva viral load by RT-PCR
Inflammatory changes [7 days]
Cytokine/ chemokine changes
Mortality [30 days]
One month mortality rate
Adverse events and serious adverse events [30 days]
Adverse events and serious adverse events within 30 days of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Recruited subjects include all adult patients ≥18 years hospitalized for virologic confirmed SARS-CoV-2 infection.
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.
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:

Inability to comprehend and to follow all required study procedures.
Allergy or severe reactions to the study drugs
Patients taking medication that will potentially interact with l interferon beta-1b or ribavirin
Pregnant or lactation women
Patients with known history of severe depression
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.
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.
Have a history of alcohol or drug abuse in the last 5 years.
Have any condition that the investigator believes may interfere with successful completion of the study.