Double Therapy With IFN-beta 1b and Hydroxychloroquine

NCT04350281 | Completed Phase 2

• 1 other identifier: UW 20-211
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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, 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. 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, the investigators 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.

Conditions

COVID

Keywords

IFN-beta 1b; hydroxychloroquine; COVID-19

Outcome Measures

Primary Outcomes (1)

• Time to negative NPS viral load

  Time to negative NPS SARS-CoV-2 viral RT-PCR

  4 weeks

Secondary Outcomes (6)

• Time to NEWS 0

  4 weeks

• Length of Hospitalisation

  4 weeks

• Time to negative viral load in all clinical samples

  4 weeks

• Adverse events

  4 weeks

• Mortality

  30 days

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

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; Drug: Hydroxychloroquine

Control group

ACTIVE COMPARATOR

Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.

Drug: Hydroxychloroquine

Interventions

Interferon Beta-1B DRUG

Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3

Treatment group

Hydroxychloroquine DRUG

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

Control group; Treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to comprehend and to follow all required study procedures.
• Allergy or severe reactions to the study drugs
• Patients with known prolonged QTc syndrome, ventricular cardiac arrhythmias, including torsade de pointes, second or third degree heart block, QTc interval \>480ms
• Patients taking medication that will potentially interact with l interferon beta-1b or hydroxychloroquine
• Patients with known underlying retinopathy
• Patients with G6PD deficiency
• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong, Queen Mary Hospital

Hong Kong, 852, Hong Kong

Location

MeSH Terms

Conditions

COVID-19

Interventions

Interferon beta-1b; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ivan FN Hung, MD FRCP

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 17, 2020
• Study Start: April 9, 2020
• Primary Completion: July 1, 2020
• Study Completion: July 7, 2020
• Last Updated: July 28, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)