COVID-19
Conditions
Keywords
Coronavirus
Brief summary
To evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.
Detailed description
Patients will attend up to 9 study visits over a period of up to 28 days.
Interventions
Peginterferon Lambda-1a (180 ug subcutaneous injection) single dose along with Standard of Care
OTHERPlacebo
Placebo subcutaneous injection along with Standard of Care Treatment for COVID-19 Infection
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Single-blind study in which only patients are blinded.
Intervention model description
An open-label, single-blind randomized controlled trial. Study participants will be randomly assigned 1:1 to a single subcutaneous dose of Peginterferon Lambda-1a or placebo along with the standard of care.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years and ≤ 75 years at the time of the assessment 2. Able and willing to understand the study, adhere to all study procedures, and provide written informed consent 3. Diagnosis of COVID-19 disease: 1. If symptomatic, the presence of mild to moderate symptoms without signs of respiratory distress, with FDA-cleared molecular diagnostic assay positive for SARS-CoV-2 within 72 hours from swab to the time of commencing informed consent: 2. If asymptomatic, initial diagnosis of SARS-CoV-2 infection with positive FDA-cleared molecular diagnostic assay obtained no more than 72 hours from initial swab to the time of commencing informed consent
Exclusion criteria
1. Patients who are hospitalized for inpatient treatment or currently being evaluated for potential hospitalization at the time of initiation of informed consent 2. Patients with a known allergy to Peginterferon Lambda-1a or any component thereof 3. Display symptoms of respiratory distress (Respiratory rate \>20, room air oxygen saturation of \<94%.) 4. Participation in a clinical trial with or use of any investigational agent within 30 days before screening 5. Treatment with interferons (IFN) within 12 months before screening 6. Previous use of Peginterferon Lambda-1a 7. History or evidence of any intolerance or hypersensitivity to IFNs or other substances contained in the study medication. 8. Female patients who are pregnant or breastfeeding. Male patients must confirm that their female sexual partners are not pregnant. 9. Current or previous history of decompensated liver disease (Child-Pugh Class B or C) or hepatocellular carcinoma 10. Co-infected with human immunodeficiency virus (HIV) 11. Significant abnormal laboratory test results at screening. 12. Other significant medical condition that may require intervention during the study 13. Concurrent use of any of the following medications: 1. Therapy with an immunomodulatory agent 2. Current use of heparin or Coumadin 3. Received blood products within 30 days before study randomization 4. Use of hematologic growth factors within 30 days before study randomization 5. Systemic antibiotics, antifungals, or antivirals for treatment of active infection within 24 hours before study randomization 6. Any prescription or herbal product that is not approved by the investigator 7. Long-term treatment (\> 2 weeks) with agents that have a high risk for nephrotoxicity or hepatotoxicity unless it is approved by the medical monitor 8. Receipt of systemic immunosuppressive therapy within 3 months before screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration Until Viral Shedding Cessation | Assessed for up to 28 days | Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sars-CoV-2 Viral Load | baseline, day 14 | Log10 Oropharyngeal viral load over time, mean change at day 14 (SD). Sars-CoV-2 RNA level in oropharyngeal and/or anterior nare swabs collected daily. |
| Area Under the Curve of SARS-COV-2 Viral Load | baseline through day 14 | Log10 viral load area under the curve through day 14, median (IQR). Area under the curve of SARS-CoV-2 viral load in oropharyngeal and/or anterior nare swabs collected daily. |
| Duration Until Resolution of Symptoms | Up to 28 days | Duration until resolution of symptoms in days, median (95% CI). Time to alleviation of all symptoms (fever, chills, cough, nasal congestion, muscle pains), defined as the time from initiation of treatment until all symptoms are rated as absent or mild in symptomatic patients. |
| Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment | 28 days | — |
Countries
United States
Participant flow
Recruitment details
Enrollment opened on April 24, 2020. The first patient was enrolled on April 25, 2020, and the last patient was enrolled on July 17, 2020.
Participants by arm
| Arm | Count |
|---|---|
| Lambda Lambda single dose administered subcutaneously in addition to standard of care treatment. | 60 |
| Placebo Placebo to match Lambda single dose administered subcutaneously in addition to standard of care treatment. | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Trial Period (28 Days) | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Lambda |
|---|---|---|---|
| Absolute lymphocyte count | 1.5 cells/μl | 1.5 cells/μl | 1.5 cells/μl |
| Age, Continuous | 36 years | 34 years | 37 years |
| Asymptomatic at baseline | 8 Participants | 2 Participants | 6 Participants |
| Body temperature ≥99.5°F | 13 Participants | 7 Participants | 6 Participants |
| Duration of symptoms prior to randomization | 5 days | 5 days | 4 days |
| Oxygen saturation | 98 percentage of peripheral capillary O2 | 99 percentage of peripheral capillary O2 | 98 percentage of peripheral capillary O2 |
| Race/Ethnicity, Customized Asian | 7 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Latinx | 75 Participants | 41 Participants | 34 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 33 Participants | 15 Participants | 18 Participants |
| Region of Enrollment United States | 120 Participants | 60 Participants | 60 Participants |
| Sex: Female, Male Female | 50 Participants | 26 Participants | 24 Participants |
| Sex: Female, Male Male | 70 Participants | 34 Participants | 36 Participants |
| Symptoms at baseline Abdominal pain | 14 Participants | 7 Participants | 7 Participants |
| Symptoms at baseline Chest pain/pressure | 27 Participants | 13 Participants | 14 Participants |
| Symptoms at baseline Chills | 49 Participants | 27 Participants | 22 Participants |
| Symptoms at baseline Cough | 69 Participants | 36 Participants | 33 Participants |
| Symptoms at baseline Decreased taste or smell | 57 Participants | 32 Participants | 25 Participants |
| Symptoms at baseline Diarrhea | 34 Participants | 18 Participants | 16 Participants |
| Symptoms at baseline Fatigue | 75 Participants | 42 Participants | 33 Participants |
| Symptoms at baseline Headache | 65 Participants | 36 Participants | 29 Participants |
| Symptoms at baseline Joint pain | 38 Participants | 19 Participants | 19 Participants |
| Symptoms at baseline Myalgias | 63 Participants | 34 Participants | 29 Participants |
| Symptoms at baseline Nausea | 34 Participants | 23 Participants | 11 Participants |
| Symptoms at baseline Rash | 9 Participants | 5 Participants | 4 Participants |
| Symptoms at baseline Runny nose | 26 Participants | 16 Participants | 10 Participants |
| Symptoms at baseline Shortness of breath | 32 Participants | 16 Participants | 16 Participants |
| Symptoms at baseline Sore throat | 45 Participants | 23 Participants | 22 Participants |
| Symptoms at baseline Vomiting | 6 Participants | 5 Participants | 1 Participants |
| White blood cell count | 5.5 cells/μl | 5.6 cells/μl | 5.5 cells/μl |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 15 / 60 | 5 / 60 |
| serious Total, serious adverse events | 2 / 60 | 2 / 60 |
Outcome results
Primary
Duration Until Viral Shedding Cessation
Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR.
Time frame: Assessed for up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lambda | Duration Until Viral Shedding Cessation | 7 days |
| Placebo | Duration Until Viral Shedding Cessation | 7 days |
p-value: 0.2995% CI: [0.56, 1.19]Regression, Cox
Secondary
Area Under the Curve of SARS-COV-2 Viral Load
Log10 viral load area under the curve through day 14, median (IQR). Area under the curve of SARS-CoV-2 viral load in oropharyngeal and/or anterior nare swabs collected daily.
Time frame: baseline through day 14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lambda | Area Under the Curve of SARS-COV-2 Viral Load | 28.5 Log10 copies*days/ml |
| Placebo | Area Under the Curve of SARS-COV-2 Viral Load | 29.6 Log10 copies*days/ml |
p-value: 0.9595% CI: [0.85, 1.16]Regression, Linear
Secondary
Change in Sars-CoV-2 Viral Load
Log10 Oropharyngeal viral load over time, mean change at day 14 (SD). Sars-CoV-2 RNA level in oropharyngeal and/or anterior nare swabs collected daily.
Time frame: baseline, day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lambda | Change in Sars-CoV-2 Viral Load | -4.3 Log10 copies per mL | Standard Deviation 1.3 |
| Placebo | Change in Sars-CoV-2 Viral Load | -4.9 Log10 copies per mL | Standard Deviation 4.7 |
p-value: 0.9195% CI: [-1.23, 1.11]Regression, Linear
Secondary
Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment
Time frame: 28 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lambda | Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment | Hospitalizations | 2 Participants |
| Lambda | Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment | Emergency Department Visits | 5 Participants |
| Placebo | Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment | Hospitalizations | 2 Participants |
| Placebo | Count of Participants Requiring Emergency Department Visits or Hospitalizations Within 28 Days of Initiation of Treatment | Emergency Department Visits | 3 Participants |
Secondary
Duration Until Resolution of Symptoms
Duration until resolution of symptoms in days, median (95% CI). Time to alleviation of all symptoms (fever, chills, cough, nasal congestion, muscle pains), defined as the time from initiation of treatment until all symptoms are rated as absent or mild in symptomatic patients.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lambda | Duration Until Resolution of Symptoms | 8 days |
| Placebo | Duration Until Resolution of Symptoms | 9 days |
p-value: 0.7695% CI: [0.6, 1.41]Regression, Cox