Borderline Personality Disorder
Conditions
Keywords
Borderline personality disorder, vafidemstat
Brief summary
PORTICO is a Phase IIb study to evaluate the efficacy and safety of vafidemstat in an adult borderline personality disorder (BPD) population.
Detailed description
PORTICO is 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.
Interventions
DRUGvafidemstat
1.2mg capsule
DRUGPlacebo
placebo capsule
Sponsors
Oryzon Genomics S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion criteria: 1. Men and women 18-65 years of age. 2. DSM-5 diagnostic criteria for BPD at least 3 months before the Screening visit. The Mini-International Neuropsychiatric Interview (MINI) will be administered at screening in order to confirm BPD diagnosis, as well as to confirm subject does not meet other relevant
Exclusion criteria
. 3. Agitation-Aggression Psychiatric Inventory-Clinician Report (AAPI-CR) Agitation \& Aggression (A/A) subscale score of ≥ 16 (severity x frequency) summed across the four (4) items comprising the A/A subscale, and the sum of the A/A subscale severity scores ≥ 6. 4. Stable living environment for \> 6 months before the Screening visit. 5. Body mass index (BMI) of at least 18.5 kg/m2, but no more than 35 kg/m2. 6. Willing and able to adhere to the prohibitions, restrictions and requirements specified in this protocol. 7. Otherwise, healthy, and medically stable based on medical history. 8. Clinical and neurological examinations and laboratory tests, as well as 12-lead ECG performed during screening that confirms subject is healthy and medically stable. 9. Able to read and write fluently and must have adequate hearing and visual acuity to complete the required testing outlined in this protocol. 10. Stable in their permitted regimen of background therapy as per drug labeling for concomitant medications at the Screening visit and they should maintain treatment throughout the study and not initiate any prohibited medications during the trial. Subjects should agree to inform their study physician of any medication changes throughout the trial. 11. Enrolled subjects will need to maintain their pre-screening psychotherapy schedule throughout the trial duration. That is, subjects receiving psychotherapy will need to have it started at least 3 months before the Screening visit and remain in psychotherapy throughout the trial. Subjects not receiving psychotherapy should not initiate psychotherapy during the trial. 12. Fertile male and female subjects must use highly efficient contraception, from the Screening visit until 30 days after last dose of the IMP, defined as: A method with less than 1% failure rate (e.g., permanent sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner) OR The use of two methods of contraception (e.g., one barrier method \[condom, diaphragm or cervical/vault caps\] with spermicide and one hormonal contraceptive \[e.g., combined oral contraceptives, patch, vaginal ring, injectable and implants\]) 13. Female subjects of childbearing potential must have a negative urine pregnancy test at screening and baseline. 14. Signed informed consent by participant prior to the initiation of any study specific procedure. Main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Difference in the CGI-S A/A From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the CGI-S A/A from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mg) and the placebo arm (full analysis set). * Full scale name: Clinical Global Impression-Severity focused on Agitation/Aggression * Scale construct: the CGI-S A/A is a clinician's global rating of the BPD patients' severity of agitation and aggression symptoms at the time of evaluation. * Scale items: 1. * Scale range values: 0 to 7. Higher scores reflect greater severity of BPD-related agitation and agression symptoms. * Scale score: 0 (min) - 7 (max). |
| Efficacy: Difference in the BPDCL-Total Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the BPDCL-Total Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mg) and the placebo arm (full analysis set). * Full scale name: Borderline Personality Disorder Checklist. * Scale construct: the BPDCL is a patient-reported outcome measure of BPD symptoms' severity over the past 2 weeks. The Total Score is a global score representing overall BPD symptom burden. * Scale items: 47 items. * Scale range values: 1 to 5 for each item. * Scale score: Total Score=47 (min) - 235 (max) as the sum of the 47 items scores. Higher scores reflect greater severity of BPD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Difference in the STAXI-2-Anger Expression Index Subscale Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to average of Weeks 8-12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
| Efficacy: Difference in the STAI-State Anxiety From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change over time on the STAI-State Anxiety and Trait Anxiety Raw Scores, from Baseline to average of Weeks 8 to 12, between active treatment arm (Vafidemstat 1.2 mg) and Placebo arm (full analysis set). * Full scale name: State-Trait Anxiety Inventory. * Scale construct: STAI is a 40-item patient-reported outcome measuring two types of anxiety: state-anxiety or current state anxiety (20 items), or trait-anxiety or general anxiety level as a personal characteristic (20 items). * Scale items: 40 items. 20 items measure state-anxiety (current), 20 items measure trait-anxiety (personal characteristic). * Scale range values: 1 to 4 per item. State-anxiety items: 1= Not At All, 4=Very Much So. Trait-anxiety items: 1=Almost Never, 4=Almost Always. * Scale score: 20 (min)-80 (max) as the sum of the 20 items scores for state-anxiety or trait-anxiety independently. State-anxiety: higher scores reflect higher current anxiety. Trait-anxiety, higher scores reflect greater tendency towards anxiety. |
| Efficacy: Difference in the CGI-S A/A Over Time (From Baseline to Week 12) | From Baseline-Week 0 to Week 12 | Change on the CGI-S A/A from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mg) and the placebo arm (full analysis set). * Full scale name: Clinical Global Impression-Severity focused on Agitation/Aggression * Scale construct: the CGI S-A/A is a clinician's global rating of the BPD patients' severity of agitation and aggression symptoms at the time of evaluation. * Scale items: 1. * Scale range values: 0 to 7. Higher scores reflect greater severity of BPD-related agitation and agression symptoms. * Scale score: 0 (min) - 7 (max). |
| Efficacy - Difference in the BPDCL-Total Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the BPDCL-Total Score from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mg) and the placebo arm (full analysis set). * Full scale name: Borderline Personality Disorder Checklist. * Scale construct: the BPDCL is a patient-reported outcome measure of BPD symptoms' severity over the past 2 weeks. The Total Score is a global score representing overall BPD symptom burden. * Scale items: 47 items. * Scale range values: 1 to 5 for each item. * Scale score: Total Score=47 (min) - 235 (max) as the sum of the 47 items scores. Higher scores reflect greater severity of BPD symptoms. |
| Efficacy: Difference in the BEST-Total Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the BEST-Total Score from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mgr) and the Placebo arm (full analysis set). * Full scale name: Borderline Evaluation of Severity Over Time. * Scale construct: the BEST is a 15-item patient-reported outcome measure of BPD symptoms' severity and coping responses over the past 2 weeks. * Scale items: 15 items comprising 3 subscales (subscale A-Thoughts and Feelings=8 items; subscale B-Negative Behaviors=4 items; subscale C-Positive Behaviors=3 items). * Scale range values: 1 to 5 for each item. * Scale score: 12 (min) - 72 (max) as per the formula 15 + A + B - C. Higher scores reflect greater severity of BPD symptoms. |
| Efficacy - Difference in the BDI-II Total Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the BDI-II-Total Score from Baseline to Week 12, between the active treatment arm (Vafidemstat 1.2 mg) and the Placebo arm (full analysis set). * Full scale name: Beck Depression Inventory-II. * Scale construct: the BDI-II is a 21-item patient-reported outcome measure of depressive symptoms' severity over the past two weeks. * Scale items: 21. * Scale range values: 0 to 3 for each item. * Scale score: 0 (min)-63 (max), sum of the 21 items scores. Higher scores reflect greater severity of depressive symptoms. |
| Efficacy: Difference in the STAXI 2-State Anger Subscale Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to Week 12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger, at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
| Efficacy: Difference in the STAXI 2-Trait Anger Subscale Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to Week 12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger, at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
| Efficacy: Difference in the STAXI 2-Anger Expression Index Subscale Score Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to Week 12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger, at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
| Efficacy: Difference in the STAI-State Anxiety Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change over time on the STAI-State Anxiety and Trait Anxiety Raw Scores, from Baseline to Week 12, between active treatment arm (Vafidemstat 1.2 mg) and Placebo arm (full analysis set). * Full scale name: State-Trait Anxiety Inventory. * Scale construct: STAI is a 40-item patient-reported outcome measuring two types of anxiety: state-anxiety or current state anxiety (20 items), or trait-anxiety or general anxiety level as a personal characteristic (20 items). * Scale items: 40 items. 20 items measure state-anxiety (current), 20 items measure trait-anxiety (personal characteristic). * Scale range values: 1 to 4 per item. State-anxiety items: 1= Not At All, 4=Very Much So. Trait-anxiety items: 1=Almost Never, 4=Almost Always. * Scale score: 20 (min)-80 (max) as the sum of the 20 items scores for state-anxiety or trait-anxiety independently. State-anxiety: higher scores reflect higher current anxiety. Trait-anxiety, higher scores reflect greater tendency towards anxiety. |
| Efficacy: Difference in the STAI-Trait Anxiety Over Time (From Baseline to Week 12) | Over time: from Baseline-Week 0 to Week 12 | Change over time on the STAI-State Anxiety and Trait Anxiety Raw Scores, from Baseline to Week 12, between active treatment arm (Vafidemstat 1.2 mg) and Placebo arm (full analysis set). * Full scale name: State-Trait Anxiety Inventory. * Scale construct: STAI is a 40-item patient-reported outcome measuring two types of anxiety: state-anxiety or current state anxiety (20 items), or trait-anxiety or general anxiety level as a personal characteristic (20 items). * Scale items: 40 items. 20 items measure state-anxiety (current), 20 items measure trait-anxiety (personal characteristic). * Scale range values: 1 to 4 per item. State-anxiety items: 1= Not At All, 4=Very Much So. Trait-anxiety items: 1=Almost Never, 4=Almost Always. * Scale score: 20 (min)-80 (max) as the sum of the 20 items scores for state-anxiety or trait-anxiety independently. State-anxiety: higher scores reflect higher current anxiety. Trait-anxiety, higher scores reflect greater tendency towards anxiety. |
| Safety: Number of Subjects Experiencing Treatment-emergent Adverse Events (TEAEs) | From Baseline-Week 0 to Week 14 | Number of subjects experiencing treatment-emergent adverse events (TEAEs) in the active treatment arm (Vafidemstat 1.2 mg) 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. TEAEs as per severity of the adverse event: mild / moderate / severe. TEAEs as per outcome of the adverse event at the end of the trial: resolved / not resolved / resolving / resolved with sequelae / outcome=death / outcome=unknown. |
| Efficacy: Difference in the BEST-Total Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the 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). * Full scale name: Borderline Evaluation of Severity Over Time. * Scale construct: the BEST is a 15-item patient-reported outcome measure of BPD symptoms' severity and coping responses over the past 2 weeks. * Scale items: 15 items comprising 3 subscales (subscale A-Thoughts and Feelings=8 items; subscale B-Negative Behaviors=4 items; subscale C-Positive Behaviors=3 items). * Scale range values: 1 to 5 for each item. Subscale A \& B: 1=None/Slight, 5=Extreme. Subscale C: 1=Almost Never, 5=Almost Always. * Scale score: 12 (min) - 72 (max) as per the formula 15 + A + B - C. Higher scores reflect greater severity of BPD symptoms.0 |
| Efficacy: Difference in the STAXI-2-State Anger Subscale Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to average of Weeks 8-12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
| Efficacy: Difference in the BDI-II Total Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the BDI-II-Total Score from Baseline to average of Weeks 8 to 12, between the active treatment arm (Vafidemstat 1.2 mg) and the Placebo arm (full analysis set). * Full scale name: Beck Depression Inventory-II. * Scale construct: the BDI-II is a 21-item patient-reported outcome measure of depressive symptoms' severity over the past two weeks. * Scale items: 21. * Scale range values: 0 to 3 for each item. * Scale score: 0 (min)-63 (max), sum of the 21 items scores. Higher scores reflect greater severity of depressive symptoms. |
| Efficacy: Difference in the STAXI-2-Trait Anger Subscale Score From Baseline to Average of Weeks 8 to 12 | From Baseline-Week 0 to average of Weeks 8 to 12 | Change on the State-Trait Anger Expression Inventory 2 (STAXI-2) State Anger (SA), Trait Anger (TA) and Anger Expression Index (AEI) Subscales from Baseline to average of Weeks 8-12 between Vafidemstat and Placebo * Construct: STAXI-2 is a 57-item patient-reported outcome measure of intensity and expression of anger as an emotional state: State Anger at that moment (how I feel right now), whereas Trait Anger reflects anger intensity and expression over a longer period of time (how I generally feel) and AEI measures how I generally behave when angry or furious. STAXI-2 was used in PORTICO as a measure of agitation and aggression * Items: SA=15; TA=10; AEI=32 (in 4 subscales: AX-O=Anger Out; AX-I=Anger In; AC-O=Anger Control Out; AC-I=Anger Control In) * Range values: 1-4 each item * Subscale scores: sum of items. SA=15 min-60 max; TA=10 min-40 max; AEI=4 subscores 8 min-32 max each, combined as AEI=(AX-O+AX-I)-(AC-O+AC-I). Higher scores mean higher agitation and aggression |
Countries
Bulgaria, Germany, Serbia, Spain, United States
Contacts
STUDY_DIRECTORMichael Ropacki, MD
Oryzon Genomics
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 30 years |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants |
| Race/Ethnicity, Customized Other | 10 Participants |
| Race/Ethnicity, Customized White | 87 Participants |
| Region of Enrollment Bulgaria | 28 participants |
| Region of Enrollment Germany | 20 participants |
| Region of Enrollment Serbia | 7 participants |
| Region of Enrollment Spain | 17 participants |
| Region of Enrollment United States | 56 participants |
| Sex: Female, Male Female | 158 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 0 / 104 |
| other Total, other adverse events | 27 / 106 | 40 / 104 |
| serious Total, serious adverse events | 1 / 106 | 0 / 104 |
Outcome results
None listed