Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

IFN-beta 1b and Remdesivir for COVID19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04647695
Recruitment Status : Recruiting
First Posted : December 1, 2020
Last Update Posted : December 10, 2020
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Covid19 Drug: Interferon beta-1b Drug: Remdesivir Phase 2

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Randomized Controlled Trial on Interferon β-1b and Remdesivir Combination Versus Remdesivir as Treatment for COVID-19 Infection
Actual Study Start Date : November 20, 2020
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. Clinical improvement [ Time Frame: 30 days ]
    Time to complete alleviation of symptoms as defined by NEWS of 0 maintained for 24 hours


Secondary Outcome Measures :
  1. Hospitalisation [ Time Frame: 30 days ]
    Length of hospitalization

  2. NPS viral load [ Time Frame: 7 days ]
    Time to negative nasopharyngeal swab (NPS) SARS-CoV-2 RT-PCR

  3. TS viral load [ Time Frame: 7 days ]
    Time to negative throat saliva (TS) SARS-CoV-2 RT-PCR

  4. Inflammatory markers [ Time Frame: 7 days ]
    Cytokine/ chemokine changes

  5. Adverse events [ Time Frame: 5 days ]
    Adverse events during treatment

  6. Mortality [ Time Frame: 30 days ]
    30-day mortality



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04647695


Contacts
Layout table for location contacts
Contact: Ivan FN Hung, MD FRCP 22554049 ivanhung@hku.hk
Contact: Kelvin KW To, MD FRCPath 22553111 kelvinto@hku.hk

Locations
Layout table for location information
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong, 852
Contact: Ivan FN Hung, MD FRCP    22554049    ivanhung@hku.hk   
Contact: Kelvin KW To, MD FRCPath    22553111    kelvinto@hku.hk   
Sponsors and Collaborators
The University of Hong Kong
Investigators
Layout table for investigator information
Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong
Publications of Results:
Other Publications:

Layout table for additonal information
Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04647695    
Other Study ID Numbers: UW 20-535
First Posted: December 1, 2020    Key Record Dates
Last Update Posted: December 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymous IPD will be shared upon request to the HKU IRB and approved by the panel
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Upon study publication for 12 months
Access Criteria: Approval by the IRB panel

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The University of Hong Kong:
COVID-19
IFN-beta 1b
remdesivir
hospitalised
Additional relevant MeSH terms:
Layout table for MeSH terms
Interferons
Interferon-beta
Interferon beta-1b
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic