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
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Interferon beta-1b Drug: Clofazimine||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||81 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Open-label randomised controlled trial|
|Masking:||None (Open Label)|
|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|
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
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
Oral 100mg twice daily on day 1, then 100mg daily for 2 days
No Intervention: Control
Standard care alone
- Clinical alleviation of symptoms [ Time Frame: 7 days ]Time to complete alleviation of symptoms as defined by NEWS of 0 maintained for 24 hours
- Hospitalisation [ Time Frame: 14 days ]Length of hospitalisation
- Time to negative viral load [ Time Frame: 7 days ]Time to negative nasopharyngeal swab, throat saliva and sputum viral load by RT-PCR
- Inflammatory changes [ Time Frame: 7 days ]Cytokine/ chemokine changes
- Mortality [ Time Frame: 30 days ]One month mortality rate
- Adverse events [ Time Frame: 30 days ]Adverse events during and shortly after treatment
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
|Contact: Ivan FN Hung, MD FRCPfirstname.lastname@example.org|
|Contact: Kelvin KW To, MD FRCPathemail@example.com|
|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 firstname.lastname@example.org|
|Principal Investigator:||Ivan FN Hung, MD FRCP||HKU|