Clinical Trial Results:
A Phase II, randomized, open–label study to evaluate the efficacy and tolerability of treatment with vafidemstat in combination with standard of care treatment to prevent Acute Respiratory Distress Syndrome (ARDS) in adult severely ill patients with COVID-19.
|
Summary
|
|
EudraCT number |
2020-001618-39 |
Trial protocol |
ES |
Global end of trial date |
31 Mar 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
20 Apr 2023
|
First version publication date |
20 Apr 2023
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
CL08-ORY-2001_COVID-19
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Oryzon Genomics S. A.
|
||
Sponsor organisation address |
Carrer de Sant Ferran, 74, CORNELLA DE LLOBREGAT, Spain, 08940
|
||
Public contact |
Douglas V. Faller, Chief Medical Officer, Oryzon Genomics S. A., 34 93 515 1313, dfaller@oryzon.com
|
||
Scientific contact |
Douglas V. Faller, Chief Medical Officer, Oryzon Genomics S. A., 34 93 515 1313, dfaller@oryzon.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Jan 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
31 Mar 2021
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To investigate the efficacy of vafidemstat, in combination with applicable standard of care treatment to prevent Acute Respiratory Distress Syndrome (ARDS) in adult severely ill patients with CoVID-19.
|
||
Protection of trial subjects |
In accordance with European Union RGPD 2016/679 of 27 April, 2016 the data were processed in accordance with the specifications outlined by the local law to ensure that requirements regarding personal data protection are met. If an external organization processed data on behalf of Oryzon, a contractual procedure was signed between Oryzon and the external organization to ensure compliance with the above-mentioned legislation. If applicable, the participation of patients in this study was reported to the appropriate local data protection agencies, in accordance with European Union RGPD 2016/679 of 27 April 2016 and Country-specific guidelines and laws (Spanish Organic Law 3/2018 of 5 December).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 May 2020
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 60
|
||
Worldwide total number of subjects |
60
|
||
EEA total number of subjects |
60
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
39
|
||
From 65 to 84 years |
21
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
The study was conducted at 7 sites in Spain. Sixty patients were assigned, 29 in the SoC + vafidemstat group and 31 in the SoC group. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
This study did not have a screening period. Patients were randomized to the study treatment after confirmation of selection criteria by investigator. Eligible patients were randomly allocated to one of two treatment groups in a 1:1 ratio (SoC: SoC + vafidemstat) by a strict order of inclusion in the study and following a randomization list. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Study Overall (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Not blinded | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
SoC + vafidemstat | |||||||||
Arm description |
Vafidemstat was administered daily for 5 days, while fasting, at a dose of 2.4 mg/day in addition to SoC. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Vafidemstat
|
|||||||||
Investigational medicinal product code |
ORY-2001
|
|||||||||
Other name |
||||||||||
Pharmaceutical forms |
Capsule
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Vafidemstat was administered daily for 5 days, at a dose of 2.4 mg/day.
|
|||||||||
|
Arm title
|
Standard of Care (SoC) | |||||||||
Arm description |
SoC referred to any standard treatment assigned by the participating hospital centers according to the current guidelines | |||||||||
Arm type |
Hospital current guidelines | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SoC + vafidemstat
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Vafidemstat was administered daily for 5 days, while fasting, at a dose of 2.4 mg/day in addition to SoC. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SoC)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SoC referred to any standard treatment assigned by the participating hospital centers according to the current guidelines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
FAS
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized patients who received at least one dose of the study treatment and with available data at Day 5 visit. Data from these patients were analyzed following the treatment planned as per randomization list.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
PPS
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized patients of the FAS who met the selection criteria and were deemed to have no major protocol violations. This was a subpopulation of the FAS. Data from these patients were analyzed following the real treatment received
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
SAF
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized patients who received at least one dose of the study treatment. Data from these patients were analyzed following the real treatment received. The SAF population was used to analyze the safety and tolerability data.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
SoC + vafidemstat
|
||
Reporting group description |
Vafidemstat was administered daily for 5 days, while fasting, at a dose of 2.4 mg/day in addition to SoC. | ||
Reporting group title |
Standard of Care (SoC)
|
||
Reporting group description |
SoC referred to any standard treatment assigned by the participating hospital centers according to the current guidelines | ||
Subject analysis set title |
FAS
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All randomized patients who received at least one dose of the study treatment and with available data at Day 5 visit. Data from these patients were analyzed following the treatment planned as per randomization list.
|
||
Subject analysis set title |
PPS
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All randomized patients of the FAS who met the selection criteria and were deemed to have no major protocol violations. This was a subpopulation of the FAS. Data from these patients were analyzed following the real treatment received
|
||
Subject analysis set title |
SAF
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomized patients who received at least one dose of the study treatment. Data from these patients were analyzed following the real treatment received. The SAF population was used to analyze the safety and tolerability data.
|
||
|
||||||||||||||||
End point title |
Reduction in the incidence of patients (%) requiring mechanical ventilation / referral to ICU [1] | |||||||||||||||
End point description |
Reduction in the incidence of patients (%) requiring mechanical ventilation and referral to ICU within the period from Day 1 (i.e.: first study drug administration) to Day 14. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From Day 1 (i.e.: first study drug administration) to Day 14
|
|||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The PPS, which matched the FAS, was considered the primary analysis population for efficacy. For continuous variables: parametric (Student’s t-test) or non-parametric tests (Mann–Whitney) for comparisons between groups and parametric (paired Student’s t-test) or non-parametric test (Wilcoxon) for comparisons between visits. For categorical variables: Chi-squared test or Fisher’s exact test for comparisons between groups. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||
End point title |
Decrease in global mortality and mortality associated to CoVID-19 pneumonias [2] | |||||||||||||||
End point description |
Decrease in global mortality and mortality associated to CoVID-19 pneumonias within the period from Day 1 (i.e.: first study drug administration) to Day 14. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From Day 1 (i.e.: first study drug administration) to Day 14
|
|||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The PPS, which matched the FAS, was considered the primary analysis population for efficacy. For continuous variables: parametric (Student’s t-test) or non-parametric tests (Mann–Whitney) for comparisons between groups and parametric (paired Student’s t-test) or non-parametric test (Wilcoxon) for comparisons between visits. For categorical variables: Chi-squared test or Fisher’s exact test for comparisons between groups. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||
End point title |
Reduction in the incidence of patients (%) requiring mechanical ventilation / referral to ICU | |||||||||||||||
End point description |
Reduction in the incidence of patients (%) requiring mechanical ventilation and referral to ICU within the period from Day 15 to Day 28. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From Day 15 to Day 28
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||
End point title |
Decrease in global mortality and mortality associated to CoVID-19 pneumonias | |||||||||||||||
End point description |
Decrease in global mortality and mortality associated to CoVID-19 pneumonias within the period from Day 15 to Day 28. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From Day 15 to Day 28
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||||||||
End point title |
Improvement in O2Sat | |||||||||||||||||||||
End point description |
Improvement in O2Sat (%) at Day 5, Day 14 and Day 28. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 5, Day 14 and Day 28
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Decrease in supplemental O2 needed | |||||||||||||||||||||
End point description |
Decrease in supplemental O2 needed at Day 5, Day 14 and Day 28. Patient with non-invasive MV During the study.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Day 5, Day 14 and Day 28
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Time to development of ARDS or respiratory failure for CoVID-19 | ||||||||||||
End point description |
Time to development of ARDS or respiratory failure for CoVID-19 requiring intubation and mechanical ventilation from Day 1 to Day 28. As all analysis sets include the same number of patients (60) no subject analysis set has been specified.
Event-free survival (EFS), defining event as: requiring invasive MV, referral to ICU, requiring rescue medication or death associated with CoVID-19 comorbidities
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 1 to Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Patients Requiring Rescue Medication | ||||||||||||
End point description |
Reduce in the incidence of patients (%) requiring rescue medication such as anti IL-6 or corticoids
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
During the Study
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Study period
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SoC + vafidemstat
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Vafidemstat was administered daily for 5 days, while fasting, at a dose of 2.4 mg/day in addition to SoC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SoC)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SoC referred to any standard treatment assigned by the participating hospital centers according to the current guidelines | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
28 Apr 2020 |
Modified inclusion criteria #2 and #5
New exclusion criteria #1 |
||
25 May 2020 |
New sample for CyTOF analysis |
||
23 Jun 2020 |
Modified inclusion criteria #2
Classification about Standard of Care Treatment |
||
29 Sep 2020 |
Modified inclusion criteria #2 and exclusion criteria #1 |
||
02 Feb 2021 |
Increase in sample size |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Limited sample size | |||
