Clinical trial NCT04362813: Study of Efficacy and Safety of Canakinumab Treatment for CRS in Participants With COVID-19-induced Pneumonia
Official title: Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia
Keywords: COVID-19
cytokine release syndrome
SARS-CoV-2
canakinumab
COVID
coronavirus
CAN-COVID
pneumonia
CRS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-04-27
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

Detailed description: This was a Phase III, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS). The study enrolled patients to canakinumab or placebo, in addition to standard of care (SOC) per local practice, which may have included anti-viral treatment, corticosteroids and/or supportive care.

Patients who met the inclusion/exclusion criteria were randomized in a 1:1 ratio to either canakinumab + SOC or placebo + SOC and were dosed immediately after ensuring that the patient met all eligibility criteria. Patients in the canakinumab arm were dosed on Day 1 with canakinumab 450 mg for body weight of 40-\<60 kg, 600 mg for 60-80 kg or 750 mg for \>80 kg in 250 mL of 5% dextrose infused IV over 2 hours. Patients in the placebo arm were administered with 250 mL of 5% dextrose infused IV over 2 hours.

The study included:

* Screening period of 0-1 day
* Study period from initial dose on Day 1 to Day 29 or hospital discharge
* Follow-up to Day 127 The primary objective was to demonstrate the benefit of canakinumab + SOC in increasing the chance of survival without ever requiring invasive mechanical ventilation among patients with COVID-19-induced pneumonia and CRS.

Eligibility criteria: Key inclusion Criteria:

* Adults ≥ 18 years old (for US only: patients ≥ 12 years old, although no children ever enrolled. This was an adult trial.)
* Body weight ≥40 kg
* Informed consent must be obtained prior to participation in this study. For US patients 12 - \< 18 years old; parent/guardian consent must be obtained and assent if applicable.
* Clinically diagnosed with SARS-CoV-2 virus by PCR or by other approved diagnostic methodology
* Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray or CT scan with pulmonary infiltrates
* SpO2 ≤ 93% on room air or arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) \< 300mmHg
* C-reactive protein ≥20 mg/L or ferritin level ≥600 µg/L

Key exclusion Criteria:

* History of hypersensitivity to canakinumab or to biologic drugs
* Intubated and on mechanical ventilation (invasive) at time of randomization
* Treatment with immunomodulators or immunosuppressant drugs, including but not limited to tocilizumab, TNF inhibitors and anti-IL-17 agents within 5 half-lives or 30 days (whichever is longer) prior to randomization with the exception of anakinra which is excluded within 5 half-lives only. Note: Immunomodulators (topical or inhaled) for asthma and atopic dermatitis and corticosteroids (any route of administration) are permitted.
* Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19

Primary outcomes:
measure: Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis
timeFrame: Day 3 to Day 29
Secondary outcomes:
measure: COVID-19-related Death After Study Treatment
timeFrame: 29 days
measure: Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP)
timeFrame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
measure: Geometric Mean Ratio to Baseline in the D-dimer
timeFrame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
measure: Geometric Mean Ratio to Baseline in Ferritin
timeFrame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: Up to day 127
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Glendale
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Brooklyn
country: United States
facility: Novartis Investigative Site
state: New York
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Toulouse Cedex 4
country: France
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: S-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sestroretsk
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: San Sebastian de los Reyes
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Barnet
country: United Kingdom
facility: Novartis Investigative Site
city: Coventry
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartiis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Sedhai YR, Sears M, Vecchie A, Bonaventura A, Greer J, Spence K, Tackett H, Turner J, Pak M, Patel N, Black M, Wohlford G, Clary RE, Duke C, Hardin M, Kemp H, Priday A, Sims EK Jr, Mihalick V, Ho AC, Ibe I, Harmon M, Markley R, Van Tassell B, Abbate A. Clinical trial enrollment at a rural satellite hospital during COVID-19 pandemic. J Clin Transl Sci. 2021 Apr 8;5(1):e136. doi: 10.1017/cts.2021.777. eCollection 2021.
citation: Caricchio R, Abbate A, Gordeev I, Meng J, Hsue PY, Neogi T, Arduino R, Fomina D, Bogdanov R, Stepanenko T, Ruiz-Seco P, Gonzalez-Garcia A, Chen Y, Li Y, Whelan S, Noviello S; CAN-COVID Investigators. Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Jul 20;326(3):230-239. doi: 10.1001/jama.2021.9508.