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Dual Therapy With Interferon Beta-1b and Clofazimine for COVID-19

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ClinicalTrials.gov Identifier: NCT04465695
Recruitment Status : Recruiting
First Posted : July 10, 2020
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
Ivan FN Hung MD, The University of Hong Kong

Brief Summary:
To conduct an open-label randomized controlled trial on a short course of interferon β-1b and clofazimine combination treatment for patients hospitalized for COVID-19 infection. To assess its safety and clinical efficacy.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Interferon beta-1b Drug: Clofazimine 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.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 HKU9-1, 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 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.

Genetic sequencing demonstrated similarity of the SARS-CoV-2 to the SARS-CoV and MERS CoV.2 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 β-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.7

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.

Another in-vitro study on an oral antimicrobial clofazimine for treatment of non-tuberculous mycobacterium infection has been proven to reduce SARS-CoV-2 viral load.

Therefore, the investigators propose to perform a prospective open-label randomised controlled trial among adult patients hospitalised after July 2020 for virologically confirmed SARS-CoV-2 infection. Patients will be randomly assigned to one of the three groups: group A: a 3-day course of 3 doses of subcutaneous injection of interferon β-1b 1mL (0.5mg; 16 million IU) consecutively on day 1 to day 3 and oral clofazimine 100mg twice daily on day 1, then 100mg daily for 2 days plus standard care, or group B: oral clofazimine 100mg twice daily on day 1, then 100mg daily for 2 days plus standard care, or group C: standard care alone (1:1:1).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open-label randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Randomised Controlled Trial on Dual Therapy With Interferon Beta-1b and Clofazimine Combination, as Treatment for COVID-19 Infection
Actual Study Start Date : July 14, 2020
Estimated Primary Completion Date : June 30, 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 clofazimine
A 3-day course of 3 doses of subcutaneous injection of interferon β-1b 1mL (0.5mg; 16 million IU) consecutively on day 1 to day 3 and oral clofazimine 100mg twice daily on day 1, then 100mg daily for 2 days plus standard care
Drug: Interferon beta-1b
Subcutaneous injection of interferon β-1b 1mL (0.5mg; 16 million IU) for 3 days

Drug: Clofazimine
Oral 100mg twice daily on day 1, then 100mg daily for 2 days

Active Comparator: Clofazimine
A 3-day course of oral clofazimine 100mg twice daily on day 1, then 100mg daily for 2 days plus standard care
Drug: Clofazimine
Oral 100mg twice daily on day 1, then 100mg daily for 2 days

No Intervention: Control
Standard care alone



Primary Outcome Measures :
  1. Clinical alleviation of symptoms [ Time Frame: 7 days ]
    Time to complete alleviation of symptoms as defined by NEWS of 0 maintained for 24 hours


Secondary Outcome Measures :
  1. Hospitalisation [ Time Frame: 14 days ]
    Length of hospitalisation

  2. Time to negative viral load [ Time Frame: 7 days ]
    Time to negative nasopharyngeal swab, throat saliva and sputum viral load by RT-PCR

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

  4. Mortality [ Time Frame: 30 days ]
    One month mortality rate

  5. Adverse events [ Time Frame: 30 days ]
    Adverse events during and shortly after treatment



Information from the National Library of Medicine

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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 or above hospitalized for virologic confirmed SARS-CoV-2 infection.
  2. 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.
  3. 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 or clofazimine
  4. Patients with known history of severe depression
  5. 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.
  6. 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.
  7. Have a history of alcohol or drug abuse in the last 5 years.
  8. 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): NCT04465695


Contacts
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Contact: Ivan FN Hung, MD FRCP 22554049 ivanhung@hku.hk
Contact: Kelvin KW To, MD FRCPath 22552584 kelvinto@hku.hk

Locations
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China, Hong Kong
The University of Hong Kong, Queen Mary Hospital Recruiting
Hong Kong, Hong Kong, China, 852
Contact: Ivan FN Hung, MD FRCP    852 22554049    ivanfn@gmail.com   
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Ivan FN Hung, MD FRCP HKU
Publications:

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Responsible Party: Ivan FN Hung MD, Clinical Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04465695    
Other Study ID Numbers: UW 20-463
First Posted: July 10, 2020    Key Record Dates
Last Update Posted: July 15, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: To share anonymised participant data
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Within 12 months of study published
Access Criteria: To be approved by the HKU/ IRB clinical trial study panel of valid research purpose

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ivan FN Hung MD, The University of Hong Kong:
COVID-19
hospitalised
IFN beta-1b
clofazimine
Additional relevant MeSH terms:
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Interferons
Interferon-beta
Clofazimine
Interferon beta-1b
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Anti-Inflammatory Agents
Leprostatic Agents
Anti-Bacterial Agents