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Study of Efficacy and Safety of DV890 in Patients With COVID-19 Pneumonia

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: NCT04382053
Recruitment Status : Completed
First Posted : May 11, 2020
Results First Posted : November 30, 2021
Last Update Posted : July 26, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition COVID-19 Pneumonia, Impaired Respiratory Function
Interventions Drug: DFV890
Drug: Standard of Care (SoC)
Enrollment 143
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.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description 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. SoC was used as an active comparator arm.
Period Title: Overall Study
Started [1] 71 72
Safety Analysis Set [2] 70 [3] 72
PD Analysis Set [4] 62 68
Completed 62 59
Not Completed 9 13
Reason Not Completed
Death             6             8
Lost to Follow-up             0             2
Protocol Deviation             1             2
Withdrawal by Subject             2             1
[1]
All randomized Participants
[2]
All randomized participants, who attended at least one post-baseline visit
[3]
One participant that was randomized to the DFV890 + SoC arm did not attend any post-baseline visit
[4]
All randomized participants with no protocol deviations with relevant impact on Pharmacodynamics (PD) data
Arm/Group Title DFV890 + SoC Standard of Care (SoC) Total
Hide Arm/Group Description 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. SoC was used as an active comparator arm. Total of all reporting groups
Overall Number of Baseline Participants 71 72 143
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 72 participants 143 participants
60.0  (13.31) 61.5  (10.38) 60.8  (11.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 72 participants 143 participants
Female
22
  31.0%
24
  33.3%
46
  32.2%
Male
49
  69.0%
48
  66.7%
97
  67.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 72 participants 143 participants
American Indian or Alaska Native
6
   8.5%
5
   6.9%
11
   7.7%
Asian
7
   9.9%
7
   9.7%
14
   9.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   4.2%
3
   4.2%
6
   4.2%
White
55
  77.5%
57
  79.2%
112
  78.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description:
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.
SoC was used as an active comparator arm.
Overall Number of Participants Analyzed 70 72
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
8.7  (1.06) 8.6  (1.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DFV890 + SoC, Standard of Care (SoC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.11
Confidence Interval (2-Sided) 90%
-2.0 to 2.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.297
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Serum C-reactive Protein (CRP) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: All randomized participants with no protocol deviations with relevant impact on PD data.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description:
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.
SoC was used as an active comparator arm.
Overall Number of Participants Analyzed 62 68
Geometric Mean (Standard Error)
Unit of Measure: Milligram / Liter
Day 2 Number Analyzed 60 participants 66 participants
31.4  (1.14) 46.6  (1.13)
Day 4 Number Analyzed 57 participants 61 participants
22.2  (1.19) 26.5  (1.18)
Day 6 Number Analyzed 52 participants 60 participants
11.5  (1.2) 15.1  (1.19)
Day 8 Number Analyzed 50 participants 55 participants
7.7  (1.25) 10.9  (1.24)
Day 10 Number Analyzed 41 participants 40 participants
7.0  (1.27) 8.0  (1.27)
Day 12 Number Analyzed 38 participants 28 participants
7.5  (1.30) 7.1  (1.31)
Day 14 Number Analyzed 34 participants 26 participants
8.1  (1.31) 6.3  (1.31)
Day 15 / end of study Number Analyzed 49 participants 51 participants
6.9  (1.27) 8.2  (1.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DFV890 + SoC, Standard of Care (SoC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.237
Comments One-sided
Method Mixed Models Analysis
Comments p-value reported is for the treatment factor across all time points
3.Secondary Outcome
Title Clinical Status Over Time
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description:
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.
SoC was used as an active comparator arm.
Overall Number of Participants Analyzed 70 72
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline 4.3  (0.49) 4.3  (0.44)
Day 2 4.3  (0.58) 4.3  (0.80)
Day 4 4.3  (0.83) 4.3  (0.95)
Day 6 3.9  (1.11) 4.2  (1.13)
Day 8 3.8  (1.31) 3.8  (1.50)
Day 10 3.6  (1.48) 3.6  (1.88)
Day 12 3.4  (1.66) 3.3  (1.98)
Day 14 3.3  (1.75) 3.1  (2.03)
Day 15 2.8  (2.02) 2.6  (2.24)
Day 17 2.7  (2.01) 2.5  (2.22)
Day 19 2.6  (2.01) 2.5  (2.27)
Day 21 2.6  (2.01) 2.5  (2.33)
Day 23 2.6  (2.03) 2.4  (2.31)
Day 25 2.6  (2.07) 2.4  (2.31)
Dy 27 2.6  (2.10) 2.4  (2.31)
Day 29 1.9  (2.34) 1.9  (2.57)
4.Secondary Outcome
Title Number of Participants Not Requiring Mechanical Ventilation for Survival
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description:
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.
SoC was used as an active comparator arm.
Overall Number of Participants Analyzed 70 72
Measure Type: Count of Participants
Unit of Measure: Participants
Until Day 15
60
  85.7%
59
  81.9%
Until Day 29
60
  85.7%
58
  80.6%
5.Secondary Outcome
Title Number of Participants With at Least One-point Improvement From Baseline in Clinical Status
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All randomized participants, who attended at least one post-baseline visit.
Arm/Group Title DFV890 + SoC Standard of Care (SoC)
Hide Arm/Group Description:
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.
SoC was used as an active comparator arm.
Overall Number of Participants Analyzed 70 72
Measure Type: Count of Participants
Unit of Measure: Participants
Day 15
59
  84.3%
53
  73.6%
Day 29
61
  87.1%
60
  83.3%
Time Frame Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 45 days.
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
 
Arm/Group Title DFV890 + SoC Standard of Care (SoC) Total
Hide Arm/Group Description 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. SoC was used as an active comparator arm. Total
All-Cause Mortality
DFV890 + SoC Standard of Care (SoC) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/70 (11.43%)   8/72 (11.11%)   16/142 (11.27%) 
Hide Serious Adverse Events
DFV890 + SoC Standard of Care (SoC) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/70 (22.86%)   11/72 (15.28%)   27/142 (19.01%) 
Cardiac disorders       
Acute myocardial infarction  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Cardiac arrest  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Cardiogenic shock  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Myocardial infarction  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
General disorders       
Condition aggravated  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Multiple organ dysfunction syndrome  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Infections and infestations       
COVID-19  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
COVID-19 pneumonia  1  2/70 (2.86%)  2/72 (2.78%)  4/142 (2.82%) 
Pneumonia  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Sepsis  1  1/70 (1.43%)  2/72 (2.78%)  3/142 (2.11%) 
Septic shock  1  1/70 (1.43%)  1/72 (1.39%)  2/142 (1.41%) 
Investigations       
Amylase increased  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Nervous system disorders       
Polyneuropathy  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Renal and urinary disorders       
Acute kidney injury  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Renal failure  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome  1  0/70 (0.00%)  2/72 (2.78%)  2/142 (1.41%) 
Acute respiratory failure  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Dyspnoea  1  1/70 (1.43%)  1/72 (1.39%)  2/142 (1.41%) 
Pulmonary embolism  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Respiratory failure  1  4/70 (5.71%)  4/72 (5.56%)  8/142 (5.63%) 
Vascular disorders       
Arterial haemorrhage  1  0/70 (0.00%)  1/72 (1.39%)  1/142 (0.70%) 
Haemodynamic instability  1  0/70 (0.00%)  2/72 (2.78%)  2/142 (1.41%) 
Peripheral artery thrombosis  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
Shock haemorrhagic  1  1/70 (1.43%)  0/72 (0.00%)  1/142 (0.70%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DFV890 + SoC Standard of Care (SoC) Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/70 (17.14%)   6/72 (8.33%)   18/142 (12.68%) 
Blood and lymphatic system disorders       
Anaemia  1  5/70 (7.14%)  5/72 (6.94%)  10/142 (7.04%) 
Metabolism and nutrition disorders       
Diabetes mellitus  1  4/70 (5.71%)  0/72 (0.00%)  4/142 (2.82%) 
Hyperglycaemia  1  4/70 (5.71%)  2/72 (2.78%)  6/142 (4.23%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778 8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT04382053    
Other Study ID Numbers: CDFV890D12201
2020-001870-32 ( EudraCT Number )
First Submitted: May 8, 2020
First Posted: May 11, 2020
Results First Submitted: November 15, 2021
Results First Posted: November 30, 2021
Last Update Posted: July 26, 2022