COVID-19 Pneumonia, Impaired Respiratory Function
Conditions
Keywords
COVID-19 pneumonia, SARS-CoV-2, APACHE II, DFV890, inflammasome
Brief summary
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.
Detailed description
This was a Phase II, randomized, controlled, open label multi-center study to assess the efficacy and safety of DFV890 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function. The study consisted of four distinct study periods: Screening / Baseline 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. Treatment period (Day 1-15): Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving either DFV890 in addition to standard of care (SoC) or SoC alone. Participants in the investigational treatment arm received DFV890 administered for a total of 14 days in addition to SoC. Participants in the control arm received SoC alone. Study assessments were conducted every 2 days for hospitalized participants. The End of Treatment (EOT) visit took place on Day 15. 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; participants continued to take the investigational treatment at home to complete the 14-day treatment period and the participants returned to the site for the Day 15/EOT assessment. If a hospital visit was not possible at Day 15, then home nursing services were used to support the last visit. 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 hospitalized participants. If participants were discharged from hospital prior to Day 29, a study visit conducted by telephone was performed on Day 29. 30-day safety follow-up assessment (Day 45): A follow-up visit for safety was conducted by telephone.
Interventions
DRUGDFV890
DFV890 25 mg tablets orally/nasogastrically administered 50 mg b.i.d for 14 days in addition to SoC.
DRUGStandard 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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum C-reactive Protein (CRP) Levels | 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 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. |
| Clinical Status Over Time | Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27 and 29 | 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. |
| Number of Participants Not Requiring Mechanical Ventilation for Survival | 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) | 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 | 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. |
Countries
Argentina, Brazil, Denmark, Germany, Hungary, India, Mexico, Netherlands, Peru, Russia, South Africa, Spain
Participant flow
Recruitment details
Participants were recruited from 30 sites in 12 countries.
Pre-assignment details
Participants underwent a Screening period of up to 24 hours which included screening and baseline assessments.
Participants by arm
| Arm | Count |
|---|---|
| DFV890 + SoC DFV890 50 mg was administered orally or nasogastrically twice per day (b.i.d) approximately 12 hours apart (morning and evening) for 14 days in addition to SoC. | 71 |
| Standard of Care (SoC) SoC was used as an active comparator arm. | 72 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 8 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Deviation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Standard of Care (SoC) | Total | DFV890 + SoC |
|---|---|---|---|
| Age, Continuous | 61.5 Years STANDARD_DEVIATION 10.38 | 60.8 Years STANDARD_DEVIATION 11.91 | 60.0 Years STANDARD_DEVIATION 13.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 14 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 112 Participants | 55 Participants |
| Sex: Female, Male Female | 24 Participants | 46 Participants | 22 Participants |
| Sex: Female, Male Male | 48 Participants | 97 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 70 | 8 / 72 | 16 / 142 |
| other Total, other adverse events | 12 / 70 | 6 / 72 | 18 / 142 |
| serious Total, serious adverse events | 16 / 70 | 11 / 72 | 27 / 142 |
Outcome results
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.
Time frame: up to Day 15
Population: Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DFV890 + SoC | APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) | 8.7 Score on a scale | Standard Error 1.06 |
| Standard of Care (SoC) | APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier) | 8.6 Score on a scale | Standard Error 1.05 |
p-value: 0.46790% CI: [-2, 2.3]ANCOVA
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.
Time frame: Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27 and 29
Population: Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DFV890 + SoC | Clinical Status Over Time | Day 29 | 1.9 Score on a scale | Standard Deviation 2.34 |
| DFV890 + SoC | Clinical Status Over Time | Day 6 | 3.9 Score on a scale | Standard Deviation 1.11 |
| DFV890 + SoC | Clinical Status Over Time | Day 14 | 3.3 Score on a scale | Standard Deviation 1.75 |
| DFV890 + SoC | Clinical Status Over Time | Day 2 | 4.3 Score on a scale | Standard Deviation 0.58 |
| DFV890 + SoC | Clinical Status Over Time | Day 4 | 4.3 Score on a scale | Standard Deviation 0.83 |
| DFV890 + SoC | Clinical Status Over Time | Day 8 | 3.8 Score on a scale | Standard Deviation 1.31 |
| DFV890 + SoC | Clinical Status Over Time | Day 10 | 3.6 Score on a scale | Standard Deviation 1.48 |
| DFV890 + SoC | Clinical Status Over Time | Day 12 | 3.4 Score on a scale | Standard Deviation 1.66 |
| DFV890 + SoC | Clinical Status Over Time | Day 15 | 2.8 Score on a scale | Standard Deviation 2.02 |
| DFV890 + SoC | Clinical Status Over Time | Day 17 | 2.7 Score on a scale | Standard Deviation 2.01 |
| DFV890 + SoC | Clinical Status Over Time | Day 19 | 2.6 Score on a scale | Standard Deviation 2.01 |
| DFV890 + SoC | Clinical Status Over Time | Day 21 | 2.6 Score on a scale | Standard Deviation 2.01 |
| DFV890 + SoC | Clinical Status Over Time | Day 23 | 2.6 Score on a scale | Standard Deviation 2.03 |
| DFV890 + SoC | Clinical Status Over Time | Day 25 | 2.6 Score on a scale | Standard Deviation 2.07 |
| DFV890 + SoC | Clinical Status Over Time | Dy 27 | 2.6 Score on a scale | Standard Deviation 2.1 |
| DFV890 + SoC | Clinical Status Over Time | Baseline | 4.3 Score on a scale | Standard Deviation 0.49 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 19 | 2.5 Score on a scale | Standard Deviation 2.27 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 14 | 3.1 Score on a scale | Standard Deviation 2.03 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 6 | 4.2 Score on a scale | Standard Deviation 1.13 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 12 | 3.3 Score on a scale | Standard Deviation 1.98 |
| Standard of Care (SoC) | Clinical Status Over Time | Dy 27 | 2.4 Score on a scale | Standard Deviation 2.31 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 21 | 2.5 Score on a scale | Standard Deviation 2.33 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 29 | 1.9 Score on a scale | Standard Deviation 2.57 |
| Standard of Care (SoC) | Clinical Status Over Time | Baseline | 4.3 Score on a scale | Standard Deviation 0.44 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 15 | 2.6 Score on a scale | Standard Deviation 2.24 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 2 | 4.3 Score on a scale | Standard Deviation 0.8 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 25 | 2.4 Score on a scale | Standard Deviation 2.31 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 4 | 4.3 Score on a scale | Standard Deviation 0.95 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 17 | 2.5 Score on a scale | Standard Deviation 2.22 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 8 | 3.8 Score on a scale | Standard Deviation 1.5 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 23 | 2.4 Score on a scale | Standard Deviation 2.31 |
| Standard of Care (SoC) | Clinical Status Over Time | Day 10 | 3.6 Score on a scale | Standard Deviation 1.88 |
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.
Time frame: 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)
Population: Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DFV890 + SoC | Number of Participants Not Requiring Mechanical Ventilation for Survival | Until Day 15 | 60 Participants |
| DFV890 + SoC | Number of Participants Not Requiring Mechanical Ventilation for Survival | Until Day 29 | 60 Participants |
| Standard of Care (SoC) | Number of Participants Not Requiring Mechanical Ventilation for Survival | Until Day 15 | 59 Participants |
| Standard of Care (SoC) | Number of Participants Not Requiring Mechanical Ventilation for Survival | Until Day 29 | 58 Participants |
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.
Time frame: Baseline, Day 15 and Day 29
Population: Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DFV890 + SoC | Number of Participants With at Least One-point Improvement From Baseline in Clinical Status | Day 15 | 59 Participants |
| DFV890 + SoC | Number of Participants With at Least One-point Improvement From Baseline in Clinical Status | Day 29 | 61 Participants |
| Standard of Care (SoC) | Number of Participants With at Least One-point Improvement From Baseline in Clinical Status | Day 15 | 53 Participants |
| Standard of Care (SoC) | Number of Participants With at Least One-point Improvement From Baseline in Clinical Status | Day 29 | 60 Participants |
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.
Time frame: Days 2, 4, 6, 8, 10, 12, 14 and 15
Population: PD analysis set: All randomized participants with no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 10 | 7.0 Milligram / Liter | Standard Error 1.27 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 14 | 8.1 Milligram / Liter | Standard Error 1.31 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 15 / end of study | 6.9 Milligram / Liter | Standard Error 1.27 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 2 | 31.4 Milligram / Liter | Standard Error 1.14 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 4 | 22.2 Milligram / Liter | Standard Error 1.19 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 6 | 11.5 Milligram / Liter | Standard Error 1.2 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 8 | 7.7 Milligram / Liter | Standard Error 1.25 |
| DFV890 + SoC | Serum C-reactive Protein (CRP) Levels | Day 12 | 7.5 Milligram / Liter | Standard Error 1.3 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 12 | 7.1 Milligram / Liter | Standard Error 1.31 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 10 | 8.0 Milligram / Liter | Standard Error 1.27 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 4 | 26.5 Milligram / Liter | Standard Error 1.18 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 14 | 6.3 Milligram / Liter | Standard Error 1.31 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 8 | 10.9 Milligram / Liter | Standard Error 1.24 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 15 / end of study | 8.2 Milligram / Liter | Standard Error 1.26 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 6 | 15.1 Milligram / Liter | Standard Error 1.19 |
| Standard of Care (SoC) | Serum C-reactive Protein (CRP) Levels | Day 2 | 46.6 Milligram / Liter | Standard Error 1.13 |
p-value: 0.237Mixed Models Analysis