A Trial of Novaferon in Asymptomatic or Mild COVID-19 Patients

Study Overview
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Brief Summary
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This is a phase III randomized, double blinded, placebo-controlled multi-center study to assess the efficacy and safety of aerosolized Novaferon for the treatment of asymptomatic or mildly patients infected with SARS-CoV-2.

Detailed Description
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Since the outbreak of New Coronavirus pneumonia (COVID-19) in late 2019, epidemics around the world are still developing. There are about 200 million confirmed cases in the world, including about 4.26 million deaths until August 5, 2021, which has become a major disaster for human being. Most of SARS-CoV-2 infection are asymptomatic or mild cases, which is the main factor causing viral transmission. Although COVID-19 patients have immune protection after cured or vaccinated, there still be a percentage of people vaccinated who still get sick, hospitalized, or die caused by COVID-19. COVID-19 vaccine breakthrough and reinfection cases became one of key problems for COVID-19 prevention and control. In addition, SARS-CoV-2 variants circulated in the world. However, some variants were associated with disease severity, the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures. Variants (e.g., Delta variant) caused some vaccine breakthrough cases. There is an urgent need for effective antiviral drugs. Novaferon is a marketed antiviral drug in China and proved to have more than ten-fold antiviral potency than that of similar interferon α-2b. Novaferon exerts antiviral activity by three ways: blocking virus entry into cells, inducing expression of antiviral genes and proteins (e.g., MX1 and OAS), and promoting apoptosis of infected cells. In vitro experimental study showed Novaferon exhibited anti-SARS-CoV-2 effects at the cellular level. A randomized, open-label, parallel-group trial demonstrated that aerosolized Novaferon expedited clearance and negative conversion of SARS-CoV-2, which provide the rational for large-scale clinical studies to verify the efficacy of Novaferon as a potential antiviral drug for COVID-19. Inhalation administration has advantages over systemic administration in reducing adverse drug reactions, promoting the distribution of drugs in respiratory tract, and thus enhancing the mucosal immunity. This is a phase III randomized, double blinded, placebo-controlled multi-center study to assess the efficacy, and safety of aerosolized Novaferon for the treatment of asymptomatic patients or patients with mild COVID-19.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Aerosolized Novaferon in Asymptomatic and Mildly Symptomatic Patients Infected With SARS-CoV-2.

Conditions
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SARS-CoV2 Infection

Intervention / Treatment
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* Drug: Recombinant cytokine gene derived protein injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:1.Patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representatives prior to initiation of any study procedures. 2.Male or female, between 18 and 65 years of age at the time of consent. 3.Laboratory-confirmed SARS-CoV-2 infection as determined by RT-PCR in nasopharyngeal or oropharyngeal swabs < 72 hours prior to enrollment. 4Patients with asymptomatics or mild COVID-19, including: Patients with asymptomatic infections refer to those with positive testing results in etiological detection of SARS-CoV-2 in swabs, but without any relevant clinical manifestations, such as self-perceived or clinically identified symptoms or signs, including fever, cough and sore throat, and without any typical imaging features of COVID-19 in their CT scans. Patients with mild SARS-COV-2 infections refer to those who are infected with SARS-COV-2 presenting mild symptoms in accordance with Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Revision 8): mild clinical symptoms, and no findings of pneumonia in chest CT images. - Exclusion Criteria:1.Patients classified into Moderate, Severe, and Critical cases according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial 8th Edition) 2.Females who are breast-feeding, lactating, pregnant or intending to become pregnant 3.Patients who are receiving any treatment with interferon or participating in other clinical studies of antiviral therapy. 4.Patients who are unable to collaborate due to poor mental health, suffering from psychiatric illness, or incapable of controlling themselves or expressing clearly. 5.Patients excluded in the opinion of the investigators. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active plus SOC<br> | Drug: Recombinant cytokine gene derived protein injection<br>* Aerosolized Novaferon, given 20 ug BID, daily for 7 days, plus Standard of Care. Inhaled Saline (placebo), given BID, daily for 7 days, plus Standard of Care.<br>* Other names: Saline;|
| Placebo Comparator: Placebo plus SOC<br> | Drug: Recombinant cytokine gene derived protein injection<br>* Aerosolized Novaferon, given 20 ug BID, daily for 7 days, plus Standard of Care. Inhaled Saline (placebo), given BID, daily for 7 days, plus Standard of Care.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of negative detection of SARS-CoV-2 RNA | Nucleic acid detection twice at a 24-hour interval | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of clinical progression | at least 4 points on 8-point ordinal Scale developed by WHO | Day 1 to Day 28 | 
| the change of viral load | viral load cannot be detected | Day 1 to Day 28 | 
| detection rate of SARS-CoV-2 RNA | cannot detect SARS-CoV-2 RNA | Day 1 to Day 28 | 
| Rate of clinical progression in patients vaccinated | Time of negative detection of SARS-CoV-2 RNA in patients vaccinated | Day 1 to Day 28 | 
| Rate of clinical progression in subgroup of patients vaccinated | at least 4 points on 8-point ordinal Scale developed by WHO | Day 1 to Day 28 | 
| Rate of clinical progression in patients infected with variants( Delta strain, et al) | at least 4 points on 8-point ordinal Scale developed by WHO | Day 1 to Day 28 | 
| Safety and tolerability | AE score | Day 1 to Day 28 |