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

NCT04354259 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 20-5334
• Study Type: interventional
• Target: 157
• Locations: 2 countries
• Sites: 7

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.

Conditions

Sars-CoV2; Covid-19

Keywords

peginterferon lambda

Outcome Measures

Primary Outcomes (4)

• Cohort A (Ambulatory) - Proportion swab negative at day 7 (Primary efficacy endpoint)

  The proportion of participants with negative SARS-CoV-2 RNA on nasopharyngeal swab.

  At day 7

• Cohort A (Ambulatory) - Treatment-emergent and treatment related serious adverse events (Primary Safety Endpoint)

  The rate of treatment-emergent and treatment-related serious adverse events (SAEs)

  Day 0 to Day 28

• Cohort B (Hospitalized) - Ordinal Scale (Primary Efficacy Endpoint)

  Clinical status on an ordinal scale at Day 14

  At Day 14

• Cohort B (Hospitalized) - treatment-emergent and treatment-related serious adverse events (Primary Safety Endpoint)

  The rate of treatment-emergent and treatment-related serious adverse events (SAEs)

  Day 0 to Day 28

Secondary Outcomes (42)

• Cohort A (Ambulatory) - Symptom Resolution (Clinical Outcome #1)

  Day 0 to Day 14

• Cohort A (Ambulatory) - Symptom severity scores (Clinical Outcome #2)

  Day 0 to Day 7

• Cohort A (Ambulatory) - Hospitalization (Clinical Outcome #3)

  Day 0 to Day 14

• Cohort A (Ambulatory) - Adverse and serious adverse events (Clinical Outcome #4)

  Day 0 to Day 14

• Cohort A (Ambulatory) - Swab negative at day 3 (Virologic/Immunological Outcome #1)

  At Day 3

Study Arms (4)

Ambulatory Cohort - Treatment

EXPERIMENTAL

to receive a single dose of peginterferon lambda 180µg SC at baseline (day 0).

Drug: Peginterferon Lambda-1A

Ambulatory Cohort - placebo

PLACEBO COMPARATOR

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

Hospitalized Cohort - Treatment

EXPERIMENTAL

To receive a dose of peginterferon lambda 180µg SC at baseline and a second dose on day 5.

Drug: Peginterferon Lambda-1A

Hospitalized Cohort - placebo

PLACEBO COMPARATOR

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 5.

Other: placebo

Interventions

Peginterferon Lambda-1A DRUG

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.

Ambulatory Cohort - Treatment; Hospitalized Cohort - Treatment

placebo OTHER

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.

Ambulatory Cohort - placebo; Hospitalized Cohort - placebo

Eligibility Criteria

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

You may qualify if:

• Adult patients between the ages of 18 and 75 years.
• Confirmed COVID-19 infection by PCR within 7 days of symptom onset (fever, respiratory symptoms, sore throat).
• Discharged to home isolation.
• Willing and able to sign informed consent.
• Willing and able to follow-up by daily phone or videoconference.
• 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. Adequate methods of contraception are:
• a. For female patients i. Hormonal contraceptives including progestogen injection (eg, Depo-Provera®), combined oral contraceptive pill or vaginal ring for ≥ 3 months before screening AND a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening, or ii. Intrauterine device (IUD) or intrauterine system (IUS) in place ≥ 3 months before screening AND a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening, or iii. Surgical sterilization of the partner (vasectomy ≥ 1 month before screening) AND a barrier method (use of condom \[male partner\] or diaphragm with spermicide or cervical cap with spermicide) from screening, or iv. Double-barrier methods (use of condom \[male partner\] with either diaphragm with spermicide or cervical cap with spermicide) from screening.
• b. For male patients i. Surgical sterilization (vasectomy ≥ 1 month before screening) AND a barrier method (use of condom or diaphragm with spermicide or cervical cap with spermicide) from screening, or ii. Consistently and correctly use a condom from screening AND female partner must agree to use a hormonal contraceptive, a nonhormonal nonbarrier method (eg, copper IUD), or a nonhormonal barrier method (eg, diaphragm with spermicide or cervical cap with spermicide).

You may not qualify if:

• Requirement for hospital admission
• Current immunosuppression due to medication (steroids, biologics, chemotherapy) or underlying condition such as organ/bone marrow transplant or untreated HIV or HIV infection with detectable HIV RNA and/or CD4 count of \<500.
• Pregnancy (or positive urine pregnancy test) or lactating
• The following pre-existing medical conditions:
• Known seizure disorder
• Known retinal disease requiring therapy
• Known autoimmune condition requiring therapy more intensive than intermittent non-steroidal anti-inflammatories in the prior 6 months (rheumatoid arthritis, lupus, inflammatory bowel disease)
• Known history of chronic obstructive pulmonary disease (COPD) or asthma associated with functional impairment
• Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy)
• Known chronic kidney disease with estimated creatinine clearance \< 50 mL/minute or need for dialysis
• Severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality
• 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
• Advanced cancer or other illness with life expectancy of \< 1 year
• Known alcohol or drug dependence that in the opinion of the investigator would impair study participation
• Known prior intolerance to interferon treatment

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Michael Garron Hospital: collaborator

Study Sites (7)

Hospital das Clínicas da Faculdade de Medicina de Botucatu

Botucatu, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, Brazil

Location

Hospital das Clínicas São Paulo

São Paulo, Brazil

Location

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Michael Garron Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (3)

• Feld JJ, Kandel C, Biondi MJ, Kozak RA, Zahoor MA, Lemieux C, Borgia SM, Boggild AK, Powis J, McCready J, Tan DHS, Chan T, Coburn B, Kumar D, Humar A, Chan A, O'Neil B, Noureldin S, Booth J, Hong R, Smookler D, Aleyadeh W, Patel A, Barber B, Casey J, Hiebert R, Mistry H, Choong I, Hislop C, Santer DM, Lorne Tyrrell D, Glenn JS, Gehring AJ, Janssen HLA, Hansen BE. Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir Med. 2021 May;9(5):498-510. doi: 10.1016/S2213-2600(20)30566-X. Epub 2021 Feb 5.

  PMID: 33556319 DERIVED

• Lee JS, Shin EC. The type I interferon response in COVID-19: implications for treatment. Nat Rev Immunol. 2020 Oct;20(10):585-586. doi: 10.1038/s41577-020-00429-3.

  PMID: 32788708 DERIVED

• Moschen AR. IBD in the time of corona - vigilance for immune-mediated diseases. Nat Rev Gastroenterol Hepatol. 2020 Sep;17(9):529-530. doi: 10.1038/s41575-020-0333-5.

  PMID: 32555385 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

peginterferon lambda-1a

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

Study Officials

• Jordan Feld, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 21, 2020
• Study Start: May 13, 2020
• Primary Completion: August 19, 2022
• Study Completion: December 8, 2022
• Last Updated: December 13, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

BR (3); CA (4)