Clinical Trial Results:
A double blind, randomized, placebo-controlled, adaptive 14-week Phase IIb trial to evaluate the efficacy and safety of vafidemstat in an adult borderline personality disorder (BPD) population (PORTICO)
Summary
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EudraCT number |
2020-003469-20 |
Trial protocol |
ES DE BG |
Global end of trial date |
13 Nov 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Jan 2025
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First version publication date |
02 Jan 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CL07-ORY-2001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04932291 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Oryzon Genomics
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Sponsor organisation address |
Sant Ferrán 74, Cornellà de Llobregat, Spain, 08940
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Public contact |
Clinical Operations, Oryzon Genomics S.A., 34 93 515 1313, sgutierrez@oryzon.com
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Scientific contact |
Chief Medical Officer, Oryzon Genomics S.A., 34 93 515 1313, mropacki@oryzon.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Jun 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Nov 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Nov 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
• To investigate the efficacy of vafidemstat in the treatment of agitation and aggression in adult BPD patients
• To investigate the efficacy of vafidemstat in the treatment of adult BPD patients
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Protection of trial subjects |
No specific protection of trial subjects was put in place
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Mar 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 17
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Country: Number of subjects enrolled |
Bulgaria: 28
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Country: Number of subjects enrolled |
Germany: 37
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Country: Number of subjects enrolled |
United States: 116
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Country: Number of subjects enrolled |
Serbia: 13
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Worldwide total number of subjects |
211
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EEA total number of subjects |
82
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
211
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Main selection criteria: adult men/ women 18-65 years; DSM-5 diagnostic criteria for BPD met at least 3 months before Screening; AAPI-CR A/A subscale score ≥16 (severity X frequency); sum of A/A subscale severity scores ≥6; mantain pre-screening psychotherapy and permitted concomitant medications, should not initiate them during the trial. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||
Arm description |
Full analysis set population | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
During the 12-week, double-blind, randomized, placebo-controlled Treatment period, from Visit 2 to Visit 8, participants were randomized to:
• Vafidemstat: participants received 1 capsule with 1.2 mg/day of vafidemstat from Monday to Friday and 1 capsule of placebo from Saturday to Sunday.
• Placebo: participants received 1 capsule of placebo per day.
During the 2-week, participant-blind, run-out safety follow-up period, from Visit 8 to Visit 9, all participants received 1 capsule of placebo per day.
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Arm title
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Vafidemstat 1.2 mgr | ||||||||||||||||||||||||||||||||||||
Arm description |
Full analysis set population | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Vafidemstat
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Investigational medicinal product code |
ORY-2001
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
During the 12-week, double-blind, randomized, placebo-controlled Treatment period, from Visit 2 to Visit 8, participants were randomized to:
• Vafidemstat: participants received 1 capsule with 1.2 mg/day of vafidemstat from Monday to Friday and 1 capsule of placebo from Saturday to Sunday.
• Placebo: participants received 1 capsule of placebo per day.
During the 2-week, participant-blind, run-out safety follow-up period, from Visit 8 to Visit 9, all participants received 1 capsule of placebo per day.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Full analysis set population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vafidemstat 1.2 mgr
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Reporting group description |
Full analysis set population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Full analysis set population | ||
Reporting group title |
Vafidemstat 1.2 mgr
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Reporting group description |
Full analysis set population |
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End point title |
Difference in the CGI-S A/A from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the placebo arm (full analysis set population)
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End point type |
Primary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
1ary endpoint: CGI-Severity Agitation/Aggression | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.2266 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.16
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.42 | ||||||||||||
upper limit |
0.1 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.133
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End point title |
Difference in the BPDCL-Total Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the Borderline Personality Disorder Checklist (BPDL) - Total Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the placebo arm (full analysis set population)
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End point type |
Primary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
1ary endpoint: BPDCL-Total Score | ||||||||||||
Comparison groups |
Vafidemstat 1.2 mgr v Placebo
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.3839 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.44
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-11.2 | ||||||||||||
upper limit |
4.34 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.941
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End point title |
Difference in the BEST-Total Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the Borderline Evaluation of Severity Over Time (BEST) - Total Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: BEST-Total Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.026 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.67
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.02 | ||||||||||||
upper limit |
-0.32 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.189
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End point title |
Difference in the BDI-II Total Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the Beck Depression Inventory – II (BDI-II) - Total Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: BDI-II Total Score | ||||||||||||
Comparison groups |
Vafidemstat 1.2 mgr v Placebo
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0944 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.61
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.68 | ||||||||||||
upper limit |
0.45 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.552
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End point title |
Difference in the STAXI-2-Anger Expression Index Raw Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) - Anger Expression Index Raw Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: STAXI-2-Anger Expression Index Raw | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0966 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.62
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.72 | ||||||||||||
upper limit |
0.48 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.569
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End point title |
Difference in the STAXI-2-State Anger Scale Raw Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) - State Anger Scale Raw Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: STAXI-2-State Anger Scale Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.5684 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.57
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.53 | ||||||||||||
upper limit |
1.39 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.991
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End point title |
Difference in the STAXI-2-Trait Anger Scale Raw Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) - Trait Anger Scale Raw Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: STAXI-2-Trait Anger Scale Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0071 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.02
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.49 | ||||||||||||
upper limit |
-0.56 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.742
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End point title |
Difference in the STAI-State Anxiety Raw Score from Baseline to average of Weeks 8 to 12 | ||||||||||||
End point description |
Change on the State-Trait Anxiety Inventory (STAI) - State Anxiety Raw Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
From Baseline-Week 0 to average of Weeks 8 to 12
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Statistical analysis title |
2ary endpoint: STAI-State Anxiety Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.2901 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.54
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-4.41 | ||||||||||||
upper limit |
1.33 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.453
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End point title |
Difference in the CGI-S A/A over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) , from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
Over time: from Baseline-Week 0 to Week 12
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Statistical analysis title |
2ary endpoint: CGI-Severity Agitation/Aggression | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.2142 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-4.21
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-12.8 | ||||||||||||
upper limit |
4.36 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
4.34
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End point title |
Difference in the BPDCL-Total Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the Borderline Personality Disorder Checklist (BPDCL), from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
Over time: from Baseline-Week 0 to Week 12
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Statistical analysis title |
2ary endpoint: BPDCL-Total Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
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Number of subjects included in analysis |
211
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.3333 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-4.21
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Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-12.8 | ||||||||||||
upper limit |
4.36 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
4.34
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End point title |
Difference in the BEST-Total Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the Borderline Evaluation of Severity Over Time (BEST)-Total Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
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End point type |
Secondary
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End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: BEST-Total Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.0384 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.71
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.27 | ||||||||||||
upper limit |
-0.15 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.296
|
|
|||||||||||||
End point title |
Difference in the BDI-II Total Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the Beck Depression Inventory – II (BDI-II) Total Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: BDI-II Total Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.1473 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.45
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.78 | ||||||||||||
upper limit |
0.87 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.684
|
|
|||||||||||||
End point title |
Difference in the STAXI-2-Anger Expression Index Raw Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the State-Trait Anger Expression Inventory 2 (STAXI-2)-Anger Expression Index Raw Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: STAXI-2-Anger Expression Index Raw | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.0851 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.05
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.53 | ||||||||||||
upper limit |
0.43 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.761
|
|
|||||||||||||
End point title |
Difference in the STAXI-2-State Anger Scale Raw Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the State-Trait Anger Expression Inventory 2 (STAXI-2)-State Anger Scale Raw Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: STAXI-2-State Anger Scale Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4157 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.84
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.88 | ||||||||||||
upper limit |
1.2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.03
|
|
|||||||||||||
End point title |
Difference in the STAXI-2-Trait Anger Scale Raw Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the State-Trait Anger Expression Inventory 2 (STAXI-2)-Trait Anger Scale Raw Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: STAXI-2-Trait Anger Scale Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.0158 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.17
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.92 | ||||||||||||
upper limit |
-0.41 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.889
|
|
|||||||||||||
End point title |
Difference in the STAI-State Anxiety Raw Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the State-Trait Anxiety Inventory (STAI) State Anxiety Raw Score, from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: STAI-State Anxiety Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4942 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.64 | ||||||||||||
upper limit |
2.25 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.745
|
|
|||||||||||||
End point title |
Difference in the STAI-Trait Anxiety Raw Score over time (from Baseline to Week 12) | ||||||||||||
End point description |
Change over time on the State-Trait Anxiety Inventory (STAI) -Trait Anxiety Raw Score from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set population)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Over time: from Baseline-Week 0 to Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
2ary endpoint: STAI-Trait Anxiety Raw Score | ||||||||||||
Comparison groups |
Placebo v Vafidemstat 1.2 mgr
|
||||||||||||
Number of subjects included in analysis |
211
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4057 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.05
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.54 | ||||||||||||
upper limit |
1.44 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.262
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects experiencing treatment-emergent adverse events (TEAEs) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of subjects experiencing treatment-emergent adverse events (TEAEs) in the active treatment arm (Vafidemstat 1.2 mgr) and the placebo arm (safety analysis set population).
Study discontinuation and study drug withdrawal are equivalent: all subjects withdrawn from study drug were discontinued from the study.
AESI: TEAEs of Special Interest.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Baseline-Week 0 to Week 14
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Treatment-emergent adverse events reported from Baseline-Week 0 to Week 14
|
||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety set population
|
||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
|
||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety set population | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vafidemstat 1.2 mgr
|
||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Safety set population | ||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Feb 2021 |
Modification of study endpoints’ evaluation times. Reason: changes on statistical methods.
Sample size increased. Reason: changes in study statistical considerations.
Amendments to Statistical Methods section. Reason: changes in study statistical considerations.
Other minor changes and clarifications in different protocol sections. |
||
12 Jul 2021 |
Addition of a paragraph on reproductive and developmental toxicology in Section 1.3. Reason: to provide a more accurate dose justification.
Addition of the CSSRS to the list of safety assessments in Section 7.3 (Safety Assessments). Reason: clarification of its safety purpose.
Addition of “Overdose should be reported as an adverse event” in Section 8.5. Reason: safety reporting clarification.
Amendments to the Statistical Methods section. Reason: to implement a more precise and appropriate statistical methodology.
Other minor changes and clarifications added to different protocol sections. |
||
28 Sep 2021 |
Update of Concomitant Medication section and addition of new text informing participants of serotoninergic syndrome. Reason: to adhere with regulatory requirements.
Update of the Laboratory Safety Assessments section. Reason: to provide clarity on safety requirements.
Modification of Statistical Analysis section. Reason: to adhere with regulatory requirements.
Update of Study Procedures to include qualitative research data obtention and update of Pharmacokinetic Assessment, only for the US sites. Reason: to adhere with regulatory requirements. |
||
08 Aug 2022 |
Changes on several includion and exclusion criteria. Reason: flexibilization of the conditions for participant inclusion.
Update of Concomitant Medication section. Reason: to account for the potential addiction to benzodiazepines.
Update of Statistical Methods and Study Design sections to further detail the Interim analysis strategy. Reason: to implement regulatory suggestions. |
||
24 May 2023 |
Update of Statistical Analysis & Determination of Sample Size sections regarding effect size and sample size: increase of sample size. Reason: to implement regulatory suggestions.
Modifications in the Concomitant Medication and Follow-up of Participants after AEs sections. Reason: to provide clarity on participants safety. |
||
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. | |||
None reported |