Study of Efficacy and Safety of MAS825 in Patients With COVID-19 (MAS-COVID)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04382651 |
|
Recruitment Status :
Completed
First Posted : May 11, 2020
Results First Posted : April 20, 2022
Last Update Posted : August 10, 2022
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| COVID-19 Pneumonia, Impaired Respiratory Function | Drug: MAS825 Other: Placebo Drug: Standard of Care (SoC) | Phase 2 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: MAS825 + SoC
Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC
|
Drug: MAS825
MAS825 liquid solution for intravenous infusion Drug: Standard of Care (SoC) 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. |
|
Placebo Comparator: Placebo + SoC
Single dose of matching Placebo by intravenous infusion in addition to SoC
|
Other: Placebo
Placebo liquid solution for intravenous infusion Drug: Standard of Care (SoC) 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. |
- APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) [ Time Frame: up to Day 15 ]
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.
- Serum C-reactive Protein (CRP) Levels [ Time Frame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15 ]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.
- Ferritin Levels [ Time Frame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15 ]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.
- Number of Participants Not Requiring Mechanical Ventilation for Survival [ Time Frame: 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 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.
- Number of Participants With at Least One-point Improvement From Baseline in Clinical Status [ Time Frame: Baseline, Day 15 and Day 29 ]
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.
- Clinical Status Over Time [ Time Frame: Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127 ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04382651
| 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 | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04382651 |
| Other Study ID Numbers: |
CMAS825F12201 |
| First Posted: | May 11, 2020 Key Record Dates |
| Results First Posted: | April 20, 2022 |
| Last Update Posted: | August 10, 2022 |
| Last Verified: | August 2022 |
| 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 |
|
COVID-19 pneumonia SARS-Cov2 |
APACHE II MAS825 inflammasome |
|
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 |