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COVID-19 Pneumonia, Impaired Respiratory FunctionPhase 2MAS-COVIDNCT04382651

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

A Phase 2 study testing MAS825 in people with COVID-19 Pneumonia, Impaired Respiratory Function, run by Novartis Pharmaceuticals at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MAS825
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
140 participants
Where
21 sitesUnited States
Study dates
11 Jun 2020to 21 Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites
  • Novartis Investigative Site

    Alexandria, Louisiana, 71301

  • Novartis Investigative Site

    Asheville, North Carolina, 28805

  • Novartis Investigative Site

    Baton Rouge, Louisiana, 70809

  • Novartis Investigative Site

    Bend, Oregon, 97701

  • Novartis Investigative Site

    Boston, Massachusetts, 02115

  • Novartis Investigative Site

    Boston, Massachusetts, 02118

  • Novartis Investigative Site

    Brooklyn, New York, 11219

  • Novartis Investigative Site

    Chula Vista, California, 91911

  • Novartis Investigative Site

    Columbus, Ohio, 43214

  • Novartis Investigative Site

    Denver, Colorado, 80220

  • Novartis Investigative Site

    Glendale, California, 91206

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Idaho Falls, Idaho, 83404

  • Novartis Investigative Site

    Irvine, California, 92697

  • Novartis Investigative Site

    La Mesa, California, 91942

  • Novartis Investigative Site

    Lafayette, Louisiana, 70596

  • Novartis Investigative Site

    Mesquite, Texas, 75149

  • Novartis Investigative Site

    Philadelphia, Pennsylvania, 19140

  • Novartis Investigative Site

    Santa Monica, California, 90404

  • Novartis Investigative Site

    Torrance, California, 90503

  • Novartis Investigative Site

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
MAS825, Placebo, Standard of Care (SoC)
Keywords
COVID-19, pneumonia, SARS-Cov2, APACHE II, MAS825, inflammasome
Medical subject headings
Respiratory Insufficiency, COVID-19, Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MAS825Drug

    MAS825 liquid solution for intravenous infusion

  • PlaceboOther

    Placebo liquid solution for intravenous infusion

  • 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.

Study groups in NCT04382651
Study groupRoleWhat they receive
MAS825 + SoCExperimentalSingle dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC
Receives: Drug: MAS825; Drug: Standard of Care (SoC)
Placebo + SoCPlacebo comparatorSingle dose of matching Placebo by intravenous infusion in addition to SoC
Receives: Other: Placebo; Drug: Standard of Care (SoC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to Day 15

Secondary outcomes (5)
  1. Serum C-reactive Protein (CRP) Levels

    C-reactive protein (CRP) is a blood test marker for inflammation in the body. It was analyzed on a log-scale fitting a repeated measures mixed model: treatment, visit, stratification factors, visit * treatment and visit * stratification factors as fixed effects and log-transformed baseline score and visit * log-transformed baseline score as continuous covariate. Values reported were back-transformed to original scale.

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

  2. Ferritin Levels

    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 was analyzed on a log-scale fitting a repeated measures mixed model: treatment, visit, stratification factors, visit * treatment and visit * stratification factors as fixed effects and log-transformed baseline score and visit * log-transformed baseline score as continuous covariate. Values reported were back-transformed to original scale.

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

  3. Number of Participants Not Requiring Mechanical Ventilation for Survival

    Number of participants not requiring mechanical ventilation for survival until Day 15 and Day 29: defined by WHO 9-point ordinal scale score of < 6 points at all time points assessments.

    The scoring is - Uninfected patients have a score 0. - Ambulatory patients 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) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support). - Patients who die have a score 8.

    Missing data values were handled as follows: For participants who died prior to Day 29, the score for death was imputed for all following visits up to and including Day 29. For all the other participants, last observation carried forward was applied up to and including Day 29.

    Measured: 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)

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

    Number of participants with at least one-point improvement from baseline in clinical status, which was measured with WHO 9-point ordinal scale.

    The scoring is - Uninfected patients have a score 0. - Ambulatory patients 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) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support). - Patients who die have a score 8.

    Missing data values were handled as follows: For participants who died prior to Day 29, the score for death was imputed for all following visits up to and including Day 29. For all the other participants, last observation carried forward was applied up to and including Day 29.

    Measured: Baseline, Day 15 and Day 29

  5. Clinical Status Over Time

    Clinical status was measured with World Health Organization (WHO) 9-point ordinal scale.

    The scoring is - Uninfected patients have a score 0. - Ambulatory patients 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) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation). - Patients who die have a score 8.

    Missing data values were handled as follows: For participants who died prior to Day 127, the score for death was imputed for all following visits up to and including Day 127. For all the other participants, last observation carried forward was applied up to and including Day 127.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2020
  2. Study start11 Jun 2020
  3. Primary completion6 Jan 2021
  4. Study completion21 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04382651
Sponsor's protocol ID
CMAS825F12201
Acronym
MAS-COVID
Status last verified
Aug 2022
First submitted
8 May 2020
Last updated
10 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37338154
  • 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.

    PubMed 34473343

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MAS825 in people with COVID-19 Pneumonia, Impaired Respiratory Function, run by Novartis Pharmaceuticals at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) (time frame: up to Day 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04382651, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2022.

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