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Double Therapy With IFN-beta 1b and Hydroxychloroquine

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ClinicalTrials.gov Identifier: NCT04350281
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Ivan FN Hung MD, The University of Hong Kong

Brief Summary:

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, 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 5 April 2020, more than 1.05 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, we 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.

A non-randomized trial has also suggested that a combination of hydroxychloroquine and azithromycin might be effective in suppressing SARS-CoV-2 viral load in patients, despite in-vitro activity was only found in hydroxychloroquine.

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


Condition or disease Intervention/treatment Phase
COVID Drug: Interferon Beta-1B Drug: Hydroxychloroquine Phase 2

Detailed Description:

This is a prospective open-label randomised controlled trial among adult patients hospitalised after April 2020 for virologically confirmed SARS-CoV-2 infection.

Patients will be randomly assigned to either the treatment group: a 3-day course of 3 doses of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care, or the control group: a 3-day course of hydroxycholoroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone (1:1).

For the control group, if the day 4 nasopharyngeal swab (NPS) viral load remains positive, then patients will receive another 3 days of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) and hydroxychloroquine 400mg daily.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 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 Hydroxychloroquine Combination Versus Hydroxychloroquine Alone, as Treatment for COVID-19 Infection
Actual Study Start Date : April 9, 2020
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Treatment group
Subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care
Drug: Interferon Beta-1B
Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3

Drug: Hydroxychloroquine
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days

Active Comparator: Control group
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.
Drug: Hydroxychloroquine
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days




Primary Outcome Measures :
  1. Time to negative NPS viral load [ Time Frame: 4 weeks ]
    Time to negative NPS SARS-CoV-2 viral RT-PCR


Secondary Outcome Measures :
  1. Time to NEWS 0 [ Time Frame: 4 weeks ]
    Time to complete allevation of symptoms as defined by NEWS of 0 maintained for 24 hours

  2. Length of Hospitalisation [ Time Frame: 4 weeks ]
    Days of hospital stay

  3. Time to negative viral load in all clinical samples [ Time Frame: 4 weeks ]
    Time to negative SARS-CoV-2 viral RT-PCR in all clinical samples

  4. Adverse events [ Time Frame: 4 weeks ]
    Treatment related adverse events

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

  6. Inflammatory markers changes [ Time Frame: 4 weeks from diagnosis ]
    Cytokine/ chemokine



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 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 with known prolonged QTc syndrome, ventricular cardiac arrhythmias, including torsade de pointes, second or third degree heart block, QTc interval >480ms
  4. Patients taking medication that will potentially interact with l interferon beta-1b or hydroxychloroquine
  5. Patients with known underlying retinopathy
  6. Patients with G6PD deficiency
  7. Patients with known history of severe depression
  8. 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.
  9. 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.
  10. Have a history of alcohol or drug abuse in the last 5 years.
  11. 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): NCT04350281


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

Locations
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Hong Kong
The University of 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       kelvinto@hku.hk   
Principal Investigator: Ivan FN Hung, MD FRCP         
Sub-Investigator: Kelvin To, MD MRCP         
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong
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Responsible Party: Ivan FN Hung MD, Professor of Medicine, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04350281    
Other Study ID Numbers: UW 20-211
First Posted: April 17, 2020    Key Record Dates
Last Update Posted: April 17, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
IFN-beta 1b, hydroxychloroquine, COVID-19
Additional relevant MeSH terms:
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Interferons
Interferon-beta
Hydroxychloroquine
Interferon beta-1b
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic