Study to Test the Efficacy and Safety of Vafidemstat in Adult Borderline Personality Disorder Population

Oryzon Genomics S.A.211 enrolled

Overview

PORTICO is a Phase IIb study to evaluate the efficacy and safety of vafidemstat in an adult borderline personality disorder (BPD) population.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

211

Conditions

Borderline Personality Disorder

Interventions

vafidemstatDRUG

1.2mg capsule

PlaceboDRUG

placebo capsule

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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 exclusion criteria 1. Failure to perform screening or baseline procedures. 2. DSM-5 diagnosis of intellectual disability, autism spectrum disorder, schizophrenia, schizoaffective disorder, bipolar disorder (or related disorders) or major depressive disorder (MDD) with psychosis. 3. Current DSM-5 diagnosis of conduct disorder, anorexia nervosa, bulimia nervosa, binge-eating disorder, oppositional defiant disorder, paranoid personality disorder or obsessive-compulsive disorder. 4. Current DSM-5 diagnosis of panic disorder or post-traumatic stress disorder (PTSD). However, subjects with PTSD, generalized anxiety disorder (GAD), social anxiety disorder (SAD), MDD without psychosis, attention deficit hyperactivity disorder (ADHD) are eligible if symptoms have been stable for at least 90 days prior to the Screening visit, these disorders are not the primary focus of treatment, changes in any treatment for these disorders would not likely be required for the duration of the study, and in the investigator´s opinion these disorders will not interfere with the assessment and/or accuracy of the study endpoints. 5. History of moderate or severe substance or alcohol use disorder according to DSM-5, with the exception of nicotine and caffeine, within 6-months before screening. 6. Use of illicit drugs for at least one week before Screening and subjects unwilling to abstain from use of these substances during the study. Use of alcohol or cannabinoids is not allowed within 24 hours prior to a study visit. Regarding cannabis, patient self-report of abstinence within 24 hours will be used for inclusion decision-making versus the urine drug test results. 7. Hospitalization or medication change for any reason, two months prior to the Screening visit or during the Screening period, that makes the subject medically or mentally unsuitable for trial participation. 8. Clinically significant, advanced or unstable disease that is likely to result in rapid deterioration of the subject's condition or affect their safety during the study. 9. Positive results for tuberculosis, Human Immunodeficiency Virus (HIV), Hepatitis C or Hepatitis B serology obtained at the Screening Visit. 10. Uncontrolled hypo- or hyperthyroidism at Screening Visit, based on laboratory parameters. 11. Clinically significant infection within the previous 30-days. 12. Chronic drug intake of specific forbidden medication 13. Esketamine in the past 90 days before the Screening visit. 14. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in the past 90 days before the screening visit. 15. Any regular intake of medications acting directly on central nervous system that investigator considers relevant to the study. 16. Member or immediate family of the study personnel or subordinate to any of the study personnel. 17. Enrollment in another investigational study or intake of investigational drug within the previous 3 months. 18. Suicide attempt within the 6-month prior to the Screening visit or significant risk of suicide. 19. Any condition that in the opinion of the investigator makes the subject unsuitable for inclusion in the study.

Locations (21)

Excell Research Inc

Oceanside, California, United States

Excell Research, Inc.

Outcomes

Primary Outcomes

Efficacy: Difference in the CGI-S A/A From Baseline 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).

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the BPDCL-Total Score From Baseline 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.

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Secondary Outcomes

Efficacy: Difference in the BEST-Total Score From Baseline 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Oceanside, California, United States

New Life Medical Research Center

Hialeah, Florida, United States

Phoenix Medical Research LLC

Miami, Florida, United States

University of Chicago Institutional Review Board

Chicago, Illinois, United States

Revive Research Institute

Elgin, Illinois, United States

Adams Clinical Trials, LLC

Watertown, Massachusetts, United States

Center for Emotioal Fitness

Cherry Hill, New Jersey, United States

Neurobehavioral Research Inc.

Cedarhurst, New York, United States

The Medical Research Network

New York, New York, United States

...and 11 more locations

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the BDI-II Total Score From Baseline 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.

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the STAXI-2-State Anger Subscale Score From Baseline 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

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the STAXI-2-Trait Anger Subscale Score From Baseline to Average of Weeks 8 to 12

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the STAXI-2-Anger Expression Index Subscale Score From Baseline to Average of Weeks 8 to 12

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the STAI-State Anxiety From Baseline 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.

Time frame: From Baseline-Week 0 to average of Weeks 8 to 12

Efficacy: Difference in the CGI-S A/A Over Time (From Baseline 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).

Time frame: From Baseline-Week 0 to Week 12

Efficacy - Difference in the BPDCL-Total Score Over Time (From Baseline 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.

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the BEST-Total Score Over Time (From Baseline 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.

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy - Difference in the BDI-II Total Score Over Time (From Baseline 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.

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the STAXI 2-State Anger Subscale Score Over Time (From Baseline 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

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the STAXI 2-Trait Anger Subscale Score Over Time (From Baseline to Week 12)

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the STAXI 2-Anger Expression Index Subscale Score Over Time (From Baseline to Week 12)

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the STAI-State Anxiety Over Time (From Baseline 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.

Time frame: Over time: from Baseline-Week 0 to Week 12

Efficacy: Difference in the STAI-Trait Anxiety Over Time (From Baseline to Week 12)

Time frame: Over time: from Baseline-Week 0 to Week 12

Safety: Number of Subjects Experiencing Treatment-emergent Adverse Events (TEAEs)

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.

Time frame: From Baseline-Week 0 to Week 14