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Interferon Lambda for Immediate Antiviral Therapy at Diagnosis in COVID-19 (ILIAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04354259
Recruitment Status : Recruiting
First Posted : April 21, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
Interferon lambda is one of the main arms of the innate antiviral immune response and is critical for controlling respiratory viral infections in mice. Interferon lambda has a better side effect profile than other interferons because of the limited tissue distribution of its receptor. Peginterferon lambda is a long-acting form that has been studied extensively in human trials in viral hepatitis, confirming its safety. We propose to evaluate peginterferon-lambda in ambulatory and hospitalized patients with mild to moderate COVID-19.

Condition or disease Intervention/treatment Phase
Sars-CoV2 Covid-19 Drug: Peginterferon Lambda-1A Other: placebo Phase 2

Detailed Description:

The study uses an adaptive design with initial enrolment in the Ambulatory cohort (Cohort A) followed by a safety assessment before initiation of enrolment in the Hospitalized cohort (Cohort B).

Ambulatory patients (Cohort A) with confirmed COVID-19 deemed well enough for home isolation will be randomized to receive a single subcutaneous injection of Peginterferon lambda 180µg or saline placebo prior to discharge. Patients will be followed remotely with visits for a repeat swab at Day 3 and 7 with the primary endpoint being the proportion positive for SARS-CoV-2 on Day 7.

Safety data will be reviewed by the Data Safety and Monitoring Committee after 50% of the Ambulatory cohort (n=60) has been enrolled. If the committee approves study continuation, enrolment will continue in the Ambulatory cohort (Cohort A) and will begin in the Hospitalized cohort (Cohort B).

Hospitalized patients (Cohort B) with moderate but not severe COVID-19 will be enrolled and randomized to Peginterferon lambda 180µg or saline placebo on Day 0 and 7. The primary endpoint will be the time to negative SARS-CoV-2 RNA by nasopharyngeal swab . In addition to the primary endpoints on which the study is powered, numerous secondary endpoints will be evaluated. Samples will also be collected for ancillary studies to better understand predictors of disease severity and response to treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Interferon Lambda for Immediate Antiviral Therapy at Diagnosis (ILIAD): A Phase II Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Effect of Peginterferon Lambda for the Treatment of COVID-19
Actual Study Start Date : May 13, 2020
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Interferon

Arm Intervention/treatment
Experimental: Ambulatory Cohort - Treatment
to receive a single dose of peginterferon lambda 180µg SC at baseline (day 0).
Drug: Peginterferon Lambda-1A
Peginterferon lambda is a covalent conjugate of human recombinant non-pegylated IFN lambda (IFN L) and a 20-kDa linear PEG chain. Peginterferon lambda Injection is a sterile, nonpyrogenic, ready-to-use solution (0.4 mg/mL) that is clear to opalescent, colorless to pale yellow, and essentially free of particles. Lambda Injection is provided in a 1-mL long Type I glass syringe (0.18 mg/syringe) with a staked 29-gauge, 1/2- inch, thin-walled needle. The syringe has a rigid needle shield and is stoppered with a plunger stopper. Syringes are prefilled with a solution of Peginterferon lambda Injection, mannitol, L-histidine, polysorbate 80, hydrochloric acid, and water for injection; they are intended for a single use at adjustable doses. The syringe is marked with dose indicator lines, which are used as a reference point for administering the correct dose.

Placebo Comparator: Ambulatory Cohort - placebo
Patients in the arm will be given a single injection of 0.9% sodium chloride (normal saline) solution at baseline (day 0). A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse.
Other: placebo
injection of 0.9% sodium chloride (normal saline) solution. A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse.

Experimental: Hospitalized Cohort - Treatment
To receive a dose of peginterferon lambda 180µg SC at baseline and a second dose on day 7.
Drug: Peginterferon Lambda-1A
Peginterferon lambda is a covalent conjugate of human recombinant non-pegylated IFN lambda (IFN L) and a 20-kDa linear PEG chain. Peginterferon lambda Injection is a sterile, nonpyrogenic, ready-to-use solution (0.4 mg/mL) that is clear to opalescent, colorless to pale yellow, and essentially free of particles. Lambda Injection is provided in a 1-mL long Type I glass syringe (0.18 mg/syringe) with a staked 29-gauge, 1/2- inch, thin-walled needle. The syringe has a rigid needle shield and is stoppered with a plunger stopper. Syringes are prefilled with a solution of Peginterferon lambda Injection, mannitol, L-histidine, polysorbate 80, hydrochloric acid, and water for injection; they are intended for a single use at adjustable doses. The syringe is marked with dose indicator lines, which are used as a reference point for administering the correct dose.

Placebo Comparator: Hospitalized Cohort - placebo
Patients in the arm will be given an injection of 0.9% sodium chloride (normal saline) solution at baseline (day 0). A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse. Patients will be administered a second dose of placebo on day 7.
Other: placebo
injection of 0.9% sodium chloride (normal saline) solution. A plastic 1 mL syringe will be prefilled by the study pharmacy. Each syringe will contain 0.5 mL (0.45 mL to match the volume of the Interferon plus 0.05 mL overfill) to allow for needle priming by the unblinded study nurse.




Primary Outcome Measures :
  1. Cohort A (Ambulatory) - Proportion swab negative at day 7 (Primary efficacy endpoint) [ Time Frame: At day 7 ]
    The proportion of participants with negative SARS-CoV-2 RNA on nasopharyngeal swab.

  2. Cohort A (Ambulatory) - Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint) [ Time Frame: Day 0 to Day 30 ]
    The rate of treatment-emergent and treatment-related serious adverse events (SAEs)

  3. Cohort B (Hospitalized) - Time to viral negativity (Primary Efficacy Endpoint) [ Time Frame: Day 0 to day 28 ]
    Time to SARS-CoV-2 RNA negativity.

  4. Cohort B (Hospitalized) - treatment-emergent and treatment-related serious adverse events (Primary Safety Endpoint) [ Time Frame: Day 0 to Day 30 ]
    The rate of treatment-emergent and treatment-related serious adverse events (SAEs)


Secondary Outcome Measures :
  1. Cohort A (Ambulatory) - Symptom Resolution (Clinical Outcome #1) [ Time Frame: Day 0 to Day 14 ]
    Time to resolution of symptoms (fever, cough, diarrhea)

  2. Cohort A (Ambulatory) - Symptom severity scores (Clinical Outcome #2) [ Time Frame: Day 0 to Day 7 ]
    Change in relative categorical symptom scores (respiratory, gastrointestinal, fever) - none, mild, moderate, severe and no change, worse, better

  3. Cohort A (Ambulatory) - Hospitalization (Clinical Outcome #3) [ Time Frame: Day 0 to Day 14 ]
    Proportion with need for hospital admission

  4. Cohort A (Ambulatory) - Adverse and serious adverse events (Clinical Outcome #4) [ Time Frame: Day 0 to Day 14 ]
    Adverse events and serious adverse events

  5. Cohort A (Ambulatory) - Swab negative at day 3 (Virologic/Immunological Outcome #1) [ Time Frame: At Day 3 ]
    Proportion negative for SARS-CoV-2 RNA by nasopharyngeal swab

  6. Cohort A (Ambulatory) - Time RNA negativity (Virologic/Immunological Outcome #2) [ Time Frame: Day 0 to Day 14 ]
    Time to SARS-CoV-2 RNA negativity on mid-turbinate nasal swab or saliva

  7. Cohort A (Ambulatory) - Proportion viremic (Virologic/Immunological Outcome #3) [ Time Frame: Day 0 and Day 7 ]
    Proportion with SARS-CoV-2 RNA in blood.

  8. Cohort A (Ambulatory) - Proportion with antibodies (Virologic/Immunological Outcome #4) [ Time Frame: Day 0 and Day 7 ]
    Proportion with SARS-CoV-2 antibodies blood

  9. Cohort A (Ambulatory) - Correlation with interferon lambda 4 genotype (Virologic/Immunological Outcome #5) [ Time Frame: Through day 7 ]
    Correlation of virologic response with interferon lambda 4 (IFNL4) genotype

  10. Cohort A (Ambulatory) - Symptoms in household contacts (Transmission Outcome #1) [ Time Frame: Day 0 to Day 14 ]
    Proportion with symptom development in household contacts (categorical symptom type yes/no)

  11. Cohort A (Ambulatory) - COVID-19 in household contacts (Transmission Outcome #2) [ Time Frame: At Day 30 ]
    Proportion with confirmed diagnosis of COVID-19 in household contacts

  12. Cohort B (Hospitalized) - ICU admission (Clinical Outcome #1) [ Time Frame: Day 0 to day 30 ]
    Proportion with ICU admission during hospitalization

  13. Cohort B (Hospitalized) - Need for intubation (Clinical Outcome #2) [ Time Frame: Day 0 to Day 14 ]
    Proportion with need for intubation

  14. Cohort B (Hospitalized) - Length of hospital stay (Clinical Outcome #3) [ Time Frame: Day 0 to Day 14 ]
    Length of hospital stay (days)

  15. Cohort B (Hospitalized) - Change in respiratory symptom score (Clinical Outcome #4) [ Time Frame: Day 0 to 7 and Day 0 to 14 ]
    Change in respiratory symptom score (score 0 to 7 with higher scores indicating more severe disease)

  16. Cohort B (Hospitalized) - Readmission to hospital (Clinical Outcome #5) [ Time Frame: By day 30 and Day 90 ]
    Proportion with readmission to hospital

  17. Cohort B (Hospitalized) - All-cause mortality (Clinical Outcome #6) [ Time Frame: At day 30 and day 90 ]
    All-cause mortality

  18. Cohort B (Hospitalized) - COVID-19-related mortality (Clinical Outcome #7) [ Time Frame: At day 30 ]
    COVID-19-related mortality

  19. Cohort B (Hospitalized) - Adverse (AEs) and Serious Adverse Events (SAEs) (Clinical Outcome #8) [ Time Frame: Day 0 to day 30 ]
    Adverse (AEs) and Serious Adverse Events (SAEs)

  20. Cohort B (Hospitalized) - Dose reduction or dose omission (Clinical Outcome #9) [ Time Frame: Day 7 to day 11 ]
    Frequency of dose reduction or dose omission for the second dose of peginterferon lambda

  21. Cohort B (Hospitalized) - Proportion negative swab. (Virologic/Immunological Outcome #1) [ Time Frame: Day 7 ]
    Proportion negative for SARS-CoV-2 RNA by nasopharyngeal swab.

  22. Cohort B (Hospitalized) - Proportion negative by day 14 (Virologic/Immunological Outcome) #2) [ Time Frame: Day 14 ]
    Proportion negative for SARS-CoV-2 by nasopharyngeal swab

  23. Cohort B (Hospitalized) - Time to negativity by rectal swab (Virologic/Immunological Outcome #3) [ Time Frame: Day 0 to day 14 ]
    Time to SARS-CoV-2 RNA negativity by rectal swab

  24. Cohort B (Hospitalized) - Correlation with interferon lambda 4 (IFNL4) genotype (Virologic/Immunological Outcome #4) [ Time Frame: Through Day 14 ]
    Correlation of virologic response with interferon lambda 4 (IFNL4) genotype

  25. Cohort B (Hospitalized) - Proportion with Antibody (Virologic/Immunological Outcome #6) [ Time Frame: At Day 7 and Day 14 ]
    Proportion with SARS-CoV-2 Antibody.

  26. Cohort B (Hospitalized) - Proportion with viremia (Virologic/Immunological Outcome #7) [ Time Frame: Day 0, Day 7, and Day 14 ]
    Proportion with SARS-CoV-2 RNA in blood



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Cohort A - Ambulatory

Inclusion Criteria

  1. Adult patients between the ages of 18 and 70 years.
  2. Confirmed COVID-19 infection by PCR within 5 days of symptom onset (fever, respiratory symptoms, sore throat).
  3. Discharged to home isolation.
  4. Willing and able to sign informed consent.
  5. Willing and able to follow-up by daily phone or videoconference.
  6. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.

Exclusion Criteria

  1. Requirement for hospital admission
  2. Current immunosuppression due to medication (steroids, biologics, chemotherapy) or underlying condition such as known HIV or organ/bone marrow transplant
  3. Pregnancy (or positive urine pregnancy test) or lactating
  4. The following pre-existing medical conditions:

    1. Known seizure disorder
    2. Known retinal disease requiring therapy
    3. Known autoimmune condition requiring therapy more intensive than intermittent non-steroidal anti-inflammatories in the prior 6 months (rheumatoid arthritis, lupus, inflammatory bowel disease)
    4. Known history of chronic obstructive pulmonary disease (COPD) or asthma associated with functional impairment or with any history of hospitalization for an exacerbation
    5. Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy)
    6. Known chronic kidney disease with estimated creatine clearance < 50 mL/minute or need for dialysis
    7. Severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality
    8. Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or psychiatric condition that in the view of the investigator would preclude use of peginterferon lambda
  5. Advanced cancer or other illness with life expectancy of < 1 year
  6. Known prior intolerance to interferon treatment
  7. Enrolment in another clinical trial with use of any investigational agent in the prior 30 days
  8. Use of off-label therapy for COVID-19

Cohort B - Hospitalized

Inclusion Criteria

  1. Adult patients over age 18
  2. SARS-CoV-2 RNA-positive on nasopharyngeal swab/respiratory specimen within 5 days of symptom onset
  3. Admitted to hospital for management of COVID-19
  4. Willing and able to provide informed consent
  5. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.

    Exclusion Criteria

  6. Severity of illness

    1. Respiratory failure (requiring>5L O2 or intubation in the ER)
    2. Shock - systolic BP<90 mmHg or mean arterial BP<60 mmHg after fluid resuscitation
  7. Current immunosuppression due to medication (steroids, biologics, chemotherapy) or underlying condition such as known HIV or organ/bone marrow transplant
  8. Pregnancy (or positive urine pregnancy test) or lactating
  9. The following pre-existing medical conditions:

    1. Known seizure disorder
    2. Known retinal disease requiring therapy
    3. Known autoimmune condition requiring therapy more intensive than intermittent non-steroidal anti-inflammatories in the prior 6 months (rheumatoid arthritis, lupus, inflammatory bowel disease)
    4. Known history of chronic obstructive pulmonary disease (COPD) or asthma associated with functional impairment or with any history of hospitalization for an exacerbation
    5. Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy)
    6. Known chronic kidney disease with estimated creatine clearance < 50 mL/minute or need for dialysis
    7. Severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality
    8. Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or psychiatric condition that in the view of the investigator would preclude use of peginterferon lambda
  10. Known alcohol or drug dependence that in the opinion of the investigator would impair study participation
  11. Known prior intolerance to interferon treatment
  12. Enrolment in another clinical trial with use of any investigational agent in the prior 30 days
  13. Use of off-label therapy for COVID-19
  14. Any of the following abnormal laboratory indices

    1. Hemoglobin < 100 mg/dL
    2. Platelet count < 75,000 cells/mm3
    3. Absolute neutrophil count < 1,000 cells/mm3
    4. Estimated creatinine clearance < 50 cc/mL
    5. Total bilirubin > 2x upper limit of normal (ULN)
    6. Alanine aminotransferase (ALT) > 10x ULN
    7. Aspartate aminotransferase (AST) > 10x ULN
    8. Lipase > 2x ULN
    9. Random blood glucose > 20 mmol/L

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): NCT04354259


Contacts
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Contact: Josh Booth (416) 340-4800 ext 6486 joshua.booth@uhn.ca

Locations
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Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Joshua Booth    416-340-4800 ext 6486    joshua.booth@uhn.ca   
Contact: Seham Noureldin, PhD    416-340-4800 ext 8681    seham.noureldin@uhnresearch.ca   
Principal Investigator: Jordan Feld, MD         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Jordan Feld, MD University Health Network, Toronto
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04354259    
Other Study ID Numbers: JF-4-2020
First Posted: April 21, 2020    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University Health Network, Toronto:
peginterferon lambda