A Phase 2 interventional study of MAS825 and Placebo in COVID-19 Pneumonia, Impaired Respiratory Function, sponsored by Novartis Pharmaceuticals. Completed at 21 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-08-10.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
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.
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 140 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
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Exclusion Criteria:
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
Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC
Drug: MAS825 · Drug: Standard of Care (SoC)
Single dose of matching Placebo by intravenous infusion in addition to SoC
Other: Placebo · Drug: Standard of Care (SoC)
MAS825 liquid solution for intravenous infusion
Placebo liquid solution for intravenous infusion
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)
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.
Time frame: up to Day 15
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.
Time frame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15
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.
Time frame: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15
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.
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 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.
Time frame: Baseline, Day 15 and Day 29
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.
Time frame: Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127
Participants took part in 21 investigative sites in 1 country, United States.
| Milestone | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Started | 69 | 71 |
| Safety analysis set | 68 | 70 |
| Pharmacokinetics (pk) analysis set | 63 | 0 |
| Completed | 38 | 43 |
| Not completed | 31 | 28 |
| Withdrew: Death | 26 | 23 |
| Withdrew: Lost to follow-up | 3 | 4 |
| Withdrew: Withdrawal by subject | 2 | 0 |
| Withdrew: Physician decision | 0 | 1 |
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.
| Score on a scale | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) | 14.5 ± 1.87 | 13.5 ± 1.8 |
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.
| Milligram / Liter | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Day 2 | 55.50 ± 1.11 | 57.70 ± 1.10 |
| Day 4 | 28.30 ± 1.19 | 37.10 ± 1.19 |
| Day 6 | 19.80 ± 1.24 | 22.30 ± 1.24 |
| Day 8 | 15.00 ± 1.31 | 16.6 ± 1.30 |
| Day 10 | 10.10 ± 1.38 | 19.80 ± 1.35 |
| Day 12 | 11.00 ± 1.42 | 15.80 ± 1.39 |
| Day 14 | 7.30 ± 1.43 | 13.20 ± 1.39 |
| Day 15 | 5.70 ± 1.40 | 11.60 ± 1.36 |
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.
| Microgram / Liter | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Day 2 | 773.20 ± 1.05 | 800.20 ± 1.05 |
| Day 4 | 692.70 ± 1.05 | 701.40 ± 1.05 |
| Day 6 | 687.50 ± 1.10 | 622.10 ± 1.10 |
| Day 8 | 674.00 ± 1.12 | 667.80 ± 1.11 |
| Day 10 | 670.00 ± 1.16 | 776.00 ± 1.15 |
| Day 12 | 680.00 ± 1.18 | 754.50 ± 1.17 |
| Day 14 | 541.70 ± 1.22 | 595.70 ± 1.22 |
| Day 15 | 502.90 ± 1.21 | 504.20 ± 1.21 |
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.
| Participants | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Until Day 15 | 41 | 47 |
| Until Day 29 | 39 | 45 |
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.
| Participants | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Day 15 | 39 | 39 |
| Day 29 | 43 | 46 |
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.
| Score on a scale | MAS825 + SoC | Placebo + SoC |
|---|---|---|
| Baseline | 4.8 ± 0.38 | 4.7 ± 0.49 |
| Day 2 | 4.8 ± 0.71 | 4.7 ± 0.57 |
| Day 4 | 4.8 ± 0.90 | 4.7 ± 1.13 |
| Day 6 | 4.8 ± 1.27 | 4.7 ± 1.40 |
| Day 8 | 4.9 ± 1.63 | 4.5 ± 1.64 |
| Day 10 | 4.9 ± 1.76 | 4.6 ± 1.80 |
| Day 12 | 5.0 ± 1.97 | 4.7 ± 2.04 |
| Day 14 | 5.0 ± 2.04 | 4.8 ± 2.09 |
| Day 15 | 4.5 ± 2.59 | 4.2 ± 2.58 |
| Day 17 | 4.4 ± 2.64 | 4.2 ± 2.67 |
| Day 19 | 4.4 ± 2.73 | 4.1 ± 2.70 |
| Day 21 | 4.4 ± 2.78 | 4.1 ± 2.71 |
| Day 23 | 4.4 ± 2.78 | 4.1 ± 2.73 |
| Day 25 | 4.4 ± 2.79 | 4.2 ± 2.76 |
| Day 27 | 4.4 ± 2.81 | 4.2 ± 2.76 |
| Day 29 | 4.2 ± 2.99 | 3.8 ± 3.00 |
| Day 45 | 4.0 ± 3.19 | 3.7 ± 3.24 |
| Day 127 | 3.8 ± 3.48 | 3.3 ± 3.41 |
Collected over Adverse events were reported from the date of administration of study treatment to day 127.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MAS825 + SoC | 26/68 (38.2%) | 31/68 (45.6%) | 20/68 (29.4%) |
| Placebo + SoC | 23/70 (32.9%) | 28/70 (40%) | 19/70 (27.1%) |
| Total | 49/138 (35.5%) | 59/138 (42.8%) | 39/138 (28.3%) |
| Event | MAS825 + SoC | Placebo + SoC | Total |
|---|---|---|---|
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 11/68 | 8/70 | 19/138 |
| Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders | 6/68 | 0/70 | 6/138 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 5/68 | 1/70 | 6/138 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 5/68 | 5/70 | 10/138 |
| COVID-19 pneumoniaInfections and infestations | 2/68 | 4/70 | 6/138 |
| Acute kidney injuryRenal and urinary disorders | 3/68 | 4/70 | 7/138 |
| Septic shockInfections and infestations | 3/68 | 0/70 | 3/138 |
| Cardiac arrestCardiac disorders | 2/68 | 3/70 | 5/138 |
| PancytopeniaBlood and lymphatic system disorders | 2/68 | 0/70 | 2/138 |
| Multiple organ dysfunction syndromeGeneral disorders | 2/68 | 1/70 | 3/138 |
| Event | MAS825 + SoC | Placebo + SoC | Total |
|---|---|---|---|
| Acute kidney injuryRenal and urinary disorders | 9/68 | 5/70 | 14/138 |
| Pneumonia bacterialInfections and infestations | 6/68 | 2/70 | 8/138 |
| AnxietyPsychiatric disorders | 3/68 | 6/70 | 9/138 |
| HypotensionVascular disorders | 5/68 | 3/70 | 8/138 |
| Urinary tract infectionInfections and infestations | 2/68 | 5/70 | 7/138 |
| Transaminases increasedInvestigations | 0/68 | 5/70 | 5/138 |
| Atrial fibrillationCardiac disorders | 4/68 | 4/70 | 8/138 |
| Age, Continuous(Years) | MAS825 + SoC | Placebo + SoC | Total |
|---|---|---|---|
| Mean | 65.3 ± 12.46 | 63.7 ± 12.91 | 64.5 ± 12.67 |
| Sex: Female, Male(Participants) | MAS825 + SoC | Placebo + SoC | Total |
|---|---|---|---|
| Female | 30 | 23 | 53 |
| Male | 39 | 48 | 87 |
| Race (NIH/OMB)(Participants) | MAS825 + SoC | Placebo + SoC | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 2 | 2 |
| Asian | 3 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 3 | 1 | 4 |
| Black or African American | 6 | 8 | 14 |
| White | 51 | 52 | 103 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 6 | 7 | 13 |
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