Clinical trial NCT04382651: Study of Efficacy and Safety of MAS825 in Patients With COVID-19
Official title: A Phase 2, Randomized, Placebo-controlled, Participant and Investigator Blinded, Multi-center Study to Assess Efficacy and Safety of MAS825 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Pneumonia, Impaired Respiratory Function
Keywords: COVID-19
pneumonia
SARS-Cov2
APACHE II
MAS825
inflammasome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-05-11
Enrollment: 140
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 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.

Detailed description: This was a Phase 2, randomized, placebo -controlled, participant and investigator blinded, multi-center study to assess efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

The study consisted of five study periods:

Screening / Baseline / Treatment visit (Day -1 to 1): Lasted up to a maximum of 24 hours and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization. Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving a single intravenous infusion of MAS825 or placebo in addition to standard of care (SoC) on Day -1 to 1.

Treatment period (Day 2-15): Study assessments were conducted every 2 days for hospitalized participants. If participants were discharged from the hospital prior to Day 15, assessments on the day of discharge were performed according to the schedule listed under Day 15 and those participants returned to the site for the Day 15 assessment (all other visits between discharge and Day 15 were omitted).

Follow-up (Day 16-29): After completion of the treatment period, participants were observed until Day 29 or discharged from hospital, whichever was sooner. Study assessments were conducted every 2 days for domiciled participants. If participants were discharged from hospital prior to Day 29, a study visit conducted by telephone was performed on Day 29 (all other visits between discharge and Day 29 were omitted).

Safety follow-up visit assessment (Day 45): A follow-up visit for safety was conducted at Day 45 if the participant was hospitalized. If participants were discharged from the hospital prior to Day 45, a study visit was conducted by telephone on Day 45.

End of Study/Safety follow-up visit assessment (Day 127): A follow-up visit for safety was conducted at Day 127 if the participant was hospitalized. If participants were discharged from the hospital prior to Day 127, a study visit was conducted by telephone on Day 127.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients aged ≥18 years at screening
2. 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)
3. 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
4. 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)
5. 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
6. Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score of ≥10 at time of screening
7. CRP ≥20 mg/L or ferritin level ≥600 μg/L at screening
8. Body weight between 45 kg and 145 kg, inclusive, at screening
9. Ability to comply with the study protocol, in the investigator's judgment

Exclusion Criteria:

1. History of hypersensitivity to the investigational treatment or their excipients or to drugs of similar chemical classes
2. Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection with the exception of SARS-CoV-2
3. In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
4. Intubated prior to randomization
5. Patients who have explicitly expressed the wish not to receive intensive care support when this would be indicated based on their condition
6. 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.
7. 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.
8. Absolute peripheral blood neutrophil count of ≤1000/mm\^3
9. Estimated GFR (eGFR) ≤30 mL/min/1.73m\^2 (based on CKD-EPI formula)
10. Pregnant or breastfeeding, or positive urine or serum pregnancy test in a pre-dose examination
11. 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
12. 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).
13. Current participation in any other investigational trials, with the exception of (not yet) approved COVID-19 therapies that are considered (local) standard of care.

Primary outcomes:
measure: APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
timeFrame: up to Day 15
Secondary outcomes:
measure: Serum C-reactive Protein (CRP) Levels
timeFrame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15
measure: Ferritin Levels
timeFrame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15
measure: Number of Participants Not Requiring Mechanical Ventilation for Survival
timeFrame: 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)
measure: Number of Participants With at Least One-point Improvement From Baseline in Clinical Status
timeFrame: Baseline, Day 15 and Day 29
measure: Clinical Status Over Time
timeFrame: Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Novartis Investigative Site
state: California
city: Glendale
country: United States
facility: Novartis Investigative Site
state: California
city: Irvine
country: United States
facility: Novartis Investigative Site
state: California
city: La Mesa
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
city: Torrance
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Washington
country: United States
facility: Novartis Investigative Site
state: District of Columbia
city: Idaho Falls
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Alexandria
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Baton Rouge
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Lafayette
country: United States
facility: Novartis Investigative Site
state: Louisiana
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: Asheville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Bend
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.