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

• ClinicalTrials.gov Identifier: NCT04382651
• Recruitment Status: Completed
• First Posted: May 11, 2020
• Last Update Posted: July 8, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function

Condition or disease	Intervention/treatment	Phase
COVID-19 Pneumonia, Impaired Respiratory Function	Drug: MAS825; Drug: Matching placebo	Phase 2

Detailed Description:

This is 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 consists of five parts:

1. Screening / Baseline / Treatment (Day -1 to 1): lasts up to a maximum of 24 hours and comprises a screening / baseline assessment. This visit will be used to confirm that the study inclusion and exclusion criteria are met and serves as baseline assessment prior to randomization. Baseline blood tests will be performed in all patients; those who screen fail because of study inclusion / exclusion criteria (e.g., serum CRP, liver function tests), will not undergo randomization. Eligible patients will receive a single i.v. infusion of MAS825 or placebo on Day -1 to 1.
2. Treatment period (Day 2-15): Study assessments to be conducted every 2 days for hospitalized patients. If patients are discharged from the hospital prior to Day 15, assessments on the day of discharge should be performed according to the schedule listed under Day 15 and patient should return to the site for the Day 15 assessment (all other visits between discharge and Day 15 can be omitted). If hospital visit is not possible at Day 15, then home nursing services may be used to support this last visit where these are available in accordance with local guidelines and should include all possible assessments (e.g. oxygen saturation with portable monitors). In case home nursing is not possible, patients will be contacted by phone on day 15.
3. Follow-up (Day 16-29): After completion of the treatment period, patients will be observed until Day 29 or discharged from hospital, whichever is sooner. Study assessments to be conducted every 2 days for domiciled patients. Where patients are discharged from hospital prior to Day 29, a study visit conducted by telephone will occur on Day 29 (all other visits between discharge and Day 29 can be omitted).
4. Safety follow-up visit assessment (Day 45): A follow-up visit will be conducted at Day 45 if the patient is hospitalized. If patients are discharged from hospital prior to Day 45, a study visit will be conducted by telephone on Day 45.
5. End of Study/Safety follow-up visit assessment (Day 127): A follow-up visit for safety will be conducted at Day 127 if the patient is hospitalized. If patients are discharged from hospital prior to Day 127, a study visit will be conducted by telephone on Day 127.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 11, 2020
• Actual Primary Completion Date: January 6, 2021
• Actual Study Completion Date: April 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: MAS825 + SoC; Single dose of MAS825 by i.v. infusion, in addition to Standard of Care (Soc)	Drug: MAS825; Single dose of MAS825 by i.v. infusion, in addition to Standard of Care (Soc)
Placebo Comparator: Matching placebo + SoC; Single dose of Matching Placebo by i.v. infusion, in addition to Standard of Care (Soc)	Drug: Matching placebo; Single dose of Matching Placebo by i.v. infusion, in addition to Standard of Care (Soc)

Outcome Measures

Primary Outcome Measures :

1. APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier) [ Time Frame: Up to 15 days ]
   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. Worst case imputation for death will be applied.

Secondary Outcome Measures :

1. Serum C-reactive protein (CRP levels) [ Time Frame: Up to 15 days ]
   C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
2. Ferritin levels [ Time Frame: Up to 15 days ]
   Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.
3. Proportion of participants without the need for invasive mechanical ventilation [ Time Frame: Day 15, Day 29 ]
   Proportion of participants without the need for invasive mechanical ventilation for survival.
4. Proportion of participants with at least one level improvement in clinical status [ Time Frame: Day 15, Day 29 ]
   Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
5. Clinical status over time [ Time Frame: Up to 15 days ]
   Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following 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.

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

Chula Vista, California, United States, 91911

Novartis Investigative Site

Glendale, California, United States, 91206

Novartis Investigative Site

Irvine, California, United States, 92697

Novartis Investigative Site

La Mesa, California, United States, 91942

Novartis Investigative Site

Santa Monica, California, United States, 90404

Novartis Investigative Site

Torrance, California, United States, 90503

United States, Colorado

Novartis Investigative Site

Denver, Colorado, United States, 80220

United States, District of Columbia

Novartis Investigative Site

Washington, District of Columbia, United States, 20037

United States, Idaho

Novartis Investigative Site

Idaho Falls, Idaho, United States, 83404

United States, Louisiana

Novartis Investigative Site

Alexandria, Louisiana, United States, 71301

Novartis Investigative Site

Baton Rouge, Louisiana, United States, 70809

Novartis Investigative Site

Lafayette, Louisiana, United States, 70596

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02115

Novartis Investigative Site

Boston, Massachusetts, United States, 02118

United States, New York

Novartis Investigative Site

Brooklyn, New York, United States, 11219

United States, North Carolina

Novartis Investigative Site

Asheville, North Carolina, United States, 28805

United States, Ohio

Novartis Investigative Site

Columbus, Ohio, United States, 43214

United States, Oregon

Novartis Investigative Site

Bend, Oregon, United States, 97701

United States, Pennsylvania

Novartis Investigative Site

Philadelphia, Pennsylvania, United States, 19140

United States, Texas

Novartis Investigative Site

Houston, Texas, United States, 77030

Novartis Investigative Site

Mesquite, Texas, United States, 75149

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD013825. doi: 10.1002/14651858.CD013825.pub2. Review.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04382651
• Other Study ID Numbers: CMAS825F12201
• First Posted: May 11, 2020
• Last Update Posted: July 8, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

COVID-19; Pneumonia; Respiratory Insufficiency; Respiratory Tract Infections; Infections; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders