Study of Efficacy and Safety of MAS825 in Patients With COVID-19

NCT04382651 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CMAS825F12201
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 21

Brief Summary

This clinical study was designed to assess the efficacy and safety of MAS825 for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infected patients with coronavirus disease 2019 (COVID-19) pneumonia and impaired respiratory function.

Conditions

COVID-19 Pneumonia, Impaired Respiratory Function

Keywords

COVID-19; pneumonia; SARS-Cov2; APACHE II; MAS825; inflammasome

Outcome Measures

Primary Outcomes (1)

• APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)

  The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.

  up to Day 15

Secondary Outcomes (5)

• Serum C-reactive Protein (CRP) Levels

  Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15

• Ferritin Levels

  Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15

• Number of Participants Not Requiring Mechanical Ventilation for Survival

  Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Additional assessments on Days 17, 19, 21, 23, 25, 27 and 29)

• Number of Participants With at Least One-point Improvement From Baseline in Clinical Status

  Baseline, Day 15 and Day 29

• Clinical Status Over Time

  Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127

Study Arms (2)

MAS825 + SoC

EXPERIMENTAL

Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC

Drug: MAS825; Drug: Standard of Care (SoC)

Placebo + SoC

PLACEBO COMPARATOR

Single dose of matching Placebo by intravenous infusion in addition to SoC

Other: Placebo; Drug: Standard of Care (SoC)

Interventions

MAS825 DRUG

MAS825 liquid solution for intravenous infusion

MAS825 + SoC

Placebo OTHER

Placebo liquid solution for intravenous infusion

Placebo + SoC

Standard of Care (SoC) DRUG

SoC included a variety of supportive therapies that ranged from the administration of supplementary oxygen to full intensive care support, alongside the use of antiviral treatment, convalescent plasma, corticosteroids, antibiotics or other agents.

MAS825 + SoC; Placebo + SoC

Eligibility Criteria

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

You may qualify if:

• Male and female patients aged ≥18 years at screening
• Signed Informed Consent Form (ICF) by patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative (if allowed according to local requirements)
• Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization
• Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan) (taken within 5 days prior to randomization)
• Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) \<300 millimeter of mercury (mmHg) at time of screening For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 \<90% and PaO2/FiO2 \<250 mmHg
• Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score of ≥10 at time of screening
• CRP ≥20 mg/L or ferritin level ≥600 μg/L at screening
• Body weight between 45 kg and 145 kg, inclusive, at screening
• Ability to comply with the study protocol, in the investigator's judgment

You may not qualify if:

• History of hypersensitivity to the investigational treatment or their excipients or to drugs of similar chemical classes
• Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection with the exception of SARS-CoV-2
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
• Intubated prior to randomization
• Patients who have explicitly expressed the wish not to receive intensive care support when this would be indicated based on their condition
• Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of anti-viral therapies or corticosteroids
• For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC
• For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily or equivalent.
• Serum alanine transaminase (ALT) or aspartate transaminase (AST) \>5 times upper limit of normal detected within 24 hours at screening/baseline (according to local laboratory reference ranges) or other evidence of severe hepatic impairment.
• Absolute peripheral blood neutrophil count of ≤1000/mm\^3
• Estimated GFR (eGFR) ≤30 mL/min/1.73m\^2 (based on CKD-EPI formula)
• Pregnant or breastfeeding, or positive urine or serum pregnancy test in a pre-dose examination
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to abstain from any sexual intercourse for a total of 29 days after randomization (the 14-day treatment period plus a 14-day follow-up period).
• Current participation in any other investigational trials, with the exception of (not yet) approved COVID-19 therapies that are considered (local) standard of care.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

Chula Vista, California, 91911, United States

Location

Novartis Investigative Site

Glendale, California, 91206, United States

Location

Novartis Investigative Site

Irvine, California, 92697, United States

Location

Novartis Investigative Site

La Mesa, California, 91942, United States

Location

Novartis Investigative Site

Santa Monica, California, 90404, United States

Location

Novartis Investigative Site

Torrance, California, 90503, United States

Location

Novartis Investigative Site

Denver, Colorado, 80220, United States

Location

Novartis Investigative Site

Washington D.C., District of Columbia, 20037, United States

Location

Novartis Investigative Site

Idaho Falls, Idaho, 83404, United States

Location

Novartis Investigative Site

Alexandria, Louisiana, 71301, United States

Location

Novartis Investigative Site

Baton Rouge, Louisiana, 70809, United States

Location

Novartis Investigative Site

Lafayette, Louisiana, 70596, 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

Asheville, North Carolina, 28805, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43214, United States

Location

Novartis Investigative Site

Bend, Oregon, 97701, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19140, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Mesquite, Texas, 75149, United States

Location

Related Publications (2)

• Hakim AD, Awili M, O'Neal HR, Siddiqi O, Jaffrani N, Lee R, Overcash JS, Chauffe A, Hammond TC, Patel B, Waters M, Criner GJ, Pachori A, Junge G, Levitch R, Watts J, Koo P, Sengupta T, Yu L, Kiffe M, Pinck A, Stein RR, Bendrick-Peart J, Jenkins J, Rowlands M, Waldron-Lynch F, Matthews J. Efficacy and safety of MAS825 (anti-IL-1beta/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function. Clin Exp Immunol. 2023 Oct 13;213(3):265-275. doi: 10.1093/cei/uxad065.

  PMID: 37338154 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

Related Links

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

MeSH Terms

Conditions

Respiratory Insufficiency; COVID-19; Pneumonia

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 11, 2020
• Study Start: June 11, 2020
• Primary Completion: January 6, 2021
• Study Completion: April 21, 2021
• Last Updated: August 10, 2022
• Results First Posted: April 20, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (21)