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

• ClinicalTrials.gov Identifier: NCT04382651
• Recruitment Status: Not yet recruiting
• First Posted: May 11, 2020
• Last Update Posted: May 11, 2020
• 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)
• Estimated Enrollment: 120 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
• Estimated Study Start Date: May 15, 2020
• Estimated Primary Completion Date: July 29, 2020
• Estimated Study Completion Date: November 5, 2020

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 to 80 Years (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 18-80 years inclusive 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
6. Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score of ≥10 at time of screening
7. CRP ≥20 mg/L and/or ferritin level ≥600 μg/L at screening
8. Body weight between 45 kg and 120 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 (besides 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 hydroxychloroquine, chloroquine or corticosteroids at doses up to and including prednisolone 10 mg daily (or equivalent for non COVID-19 disorders)
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 (Child-Pugh Class C)
8. Absolute peripheral blood neutrophil count of ≤1000/mm3
9. Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (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).

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

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

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:

Pneumonia; Respiratory Insufficiency; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Respiration Disorders