Study of Efficacy and Safety of Canakinumab Treatment for CRS in Participants With COVID-19-induced Pneumonia

NCT04362813 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CACZ885D23102020-001370-30
• Study Type: interventional
• Target: 454
• Locations: 6 countries
• Sites: 39

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).

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

Outcome Measures

Primary Outcomes (1)

• Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis

  Number of responders who survived without requiring invasive mechanical ventilation from Day 3 to Day 29. An early dropout without requiring invasive mechanical ventilation is considered as a responder if discharged from hospital with 9-point ordinal scale\<=1 or with last 9-point ordinal scale on/after Day 15 better than baseline.

  Day 3 to Day 29

Secondary Outcomes (5)

• COVID-19-related Death After Study Treatment

  29 days

• Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP)

  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.

• Geometric Mean Ratio to Baseline in the D-dimer

  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.

• Geometric Mean Ratio to Baseline in Ferritin

  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.

• Number of Participants With Treatment Emergent Adverse Events

  Up to day 127

Study Arms (2)

Canakinumab

EXPERIMENTAL

Canakinumab 450 mg for body weight 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. Single dose on Day 1.

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.

Drug: Placebo

Interventions

Canakinumab DRUG

Canakinumab 450 mg for body weight 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. Single dose on Day 1.

Also known as: ACZ885

Canakinumab

Placebo DRUG

250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (39)

Novartis Investigative Site

Birmingham, Alabama, 35294, United States

Location

Novartis Investigative Site

Glendale, California, 91206, United States

Location

Novartis Investigative Site

San Francisco, California, 94110, United States

Location

Novartis Investigative Site

San Francisco, California, 94143, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60611, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21201, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02118, United States

Location

Novartis Investigative Site

Brooklyn, New York, 11219, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44106-5000, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19140, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Richmond, Virginia, 23298, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Bergamo, BG, 24127, Italy

Location

Novartis Investigative Site

Cona, FE, 44100, Italy

Location

Novartis Investigative Site

Barnaul, 656045, Russia

Location

Novartis Investigative Site

Moscow, 111539, Russia

Location

Novartis Investigative Site

Moscow, 121309, Russia

Location

Novartis Investigative Site

Moscow, 123056, Russia

Location

Novartis Investigative Site

Moscow, 123182, Russia

Location

Novartis Investigative Site

Ryazan, 390039, Russia

Location

Novartis Investigative Site

S-Petersburg, 194354, Russia

Location

Novartis Investigative Site

Saint Petersburg, 193312, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Sestroretsk, 197706, Russia

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

San Sebastián de los Reyes, Madrid, 28702, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Barnet, EN5 3DJ, United Kingdom

Location

Novartis Investigative Site

Coventry, CV2 2DX, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

London, NW3 2QG, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34367680 DERIVED

• 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.

  PMID: 34283183 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Cytokine Release Syndrome; COVID-19; Coronavirus Infections; Pneumonia

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

(862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartiis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 27, 2020
• Study Start: April 30, 2020
• Primary Completion: September 16, 2020
• Study Completion: December 22, 2020
• Last Updated: January 24, 2022
• Results First Posted: August 16, 2021

Record last verified: 2022-01

Locations

RU (10); US (15); ES (6); GB (5); FR (1); IT (2)