COVID-19 Pneumonia, Impaired Respiratory Function Clinical Trial
Official title:
Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function
Verified date | June 2022 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This clinical study was designed to assess the efficacy and safety of DFV890 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.
Status | Completed |
Enrollment | 143 |
Est. completion date | December 24, 2020 |
Est. primary completion date | December 10, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | Inclusion Criteria: - Male and female patients aged 18-80 years inclusive at screening. - 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 (within 24 hours in patients in the Netherlands). - 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 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. - APACHE II score of =10 at screening. - C-reactive protein (CRP) =20 mg/L and/or ferritin level =600 µg/L at screening. - Body mass index of =18 to <40kg/m2 at screening. Exclusion Criteria: - Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides 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. - 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: 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. In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past 2 weeks are exclusionary. - Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline (according to local laboratory reference ranges) or other evidence if severe hepatic impairment (Child-Pugh Class C). - Absolute peripheral blood neutrophil count of =1000/mm3. - Estimated GFR (eGFR) =30 mL/min/1.73m2 (based on CKD-EPI formula). - Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment. - Patients with innate or acquired immunodeficiencies. - Patients who have undergone solid organ or stem cell transplantation. |
Country | Name | City | State |
---|---|---|---|
Argentina | Novartis Investigative Site | Buenos Aires | |
Argentina | Novartis Investigative Site | Caba | Buenos Aires |
Brazil | Novartis Investigative Site | Porto Alegre | RS |
Brazil | Novartis Investigative Site | Sao Paulo | SP |
Denmark | Novartis Investigative Site | Hvidovre | |
Germany | Novartis Investigative Site | Hannover | |
Germany | Novartis Investigative Site | Regensburg | Bavaria |
Germany | Novartis Investigative Site | Wuerzburg | |
Hungary | Novartis Investigative Site | Budapest | |
India | Novartis Investigative Site | Coimbatore | Tamil Nadu |
India | Novartis Investigative Site | Kolkata | West Bengal |
India | Novartis Investigative Site | New Delhi | |
India | Novartis Investigative Site | New Delhi | |
Mexico | Novartis Investigative Site | Ciudad de Mexico | Mexico CP |
Mexico | Novartis Investigative Site | Monterrey | Nuevo Leon |
Netherlands | Novartis Investigative Site | Harderwijk | |
Peru | Novartis Investigative Site | San Martin de Porres | Lima |
Peru | Novartis Investigative Site | San Miguel | Lima |
Russian Federation | Novartis Investigative Site | Barnaul | |
Russian Federation | Novartis Investigative Site | Chelyabinsk | |
Russian Federation | Novartis Investigative Site | Ekaterinburg | |
Russian Federation | Novartis Investigative Site | Krasnoyarsk | |
Russian Federation | Novartis Investigative Site | Moscow | |
Russian Federation | Novartis Investigative Site | Ryazan | |
Russian Federation | Novartis Investigative Site | Saint Petersburg | |
Russian Federation | Novartis Investigative Site | St Petersburg | |
South Africa | Novartis Investigative Site | George | Western Cape |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Madrid |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
Argentina, Brazil, Denmark, Germany, Hungary, India, Mexico, Netherlands, Peru, Russian Federation, South Africa, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. |
up to Day 15 | |
Secondary | 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 including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate. Values reported were back-transformed to original scale. | Days 2, 4, 6, 8, 10, 12, 14 and 15 | |
Secondary | 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 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. |
Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27 and 29 | |
Secondary | 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. |
Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Assessments on Days 17, 19, 21, 23, 25, 27 and 29) | |
Secondary | 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. |
Baseline, Day 15 and Day 29 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04382651 -
Study of Efficacy and Safety of MAS825 in Patients With COVID-19
|
Phase 2 |