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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Borderline Personality Disorder

Intervention / Treatment
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* Drug: vafidemstat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Principal inclusion criteria: Men and women 18-65 years of age. 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. 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. Outpatient known to the site or investigator and has been treated by the site or investigator for at least the last 3 months prior to the Screening visit. Stable living environment for > 6 months before the Screening visit. Body mass index (BMI) of at least 18.5 kg/m2, but no more than 35 kg/m2. Willing and able to adhere to the prohibitions, restrictions and requirements specified in this protocol. Otherwise, healthy, and medically stable based on medical history. Clinical and neurological examinations and laboratory tests, as well as 12-lead ECG performed during screening that confirms subject is healthy and medically stable. Able to read and write fluently and must have adequate hearing and visual acuity to complete the required testing outlined in this protocol. 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. 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. 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]) Female subjects of childbearing potential must have a negative urine pregnancy test at screening and baseline. Signed informed consent by participant prior to the initiation of any study specific procedure. Principal exclusion criteria DSM-5 diagnosis of intellectual disability, autism spectrum disorder, schizophrenia, schizoaffective disorder, bipolar disorder (or related disorders) or major depressive disorder (MDD) with psychosis. Current DSM-5 diagnosis of conduct disorder, anorexia nervosa, bulimia nervosa, binge-eating disorder, oppositional defiant disorder, paranoid personality disorder or obsessive-compulsive disorder. 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. 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. Use of illicit drugs for at least one week before Screening and subjects unwilling to abstain from use of these substances during the study. 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. 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. Positive results for tuberculosis, Human Immunodeficiency Virus (HIV), Hepatitis C or Hepatitis B serology obtained at the Screening Visit. Uncontrolled hypo- or hyperthyroidism at Screening Visit, based on laboratory parameters. Clinically significant infection within the previous 30-days. Chronic drug intake of specific forbidden medication Esketamine in the past 90 days before the Screening visit. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in the past 90 days before the screening visit. Any regular intake of medications acting directly on central nervous system that investigator considers relevant to the study. Member or immediate family of the study personnel or subordinate to any of the study personnel. Enrollment in another investigational study or intake of investigational drug within the previous 3 months. Suicide attempt within the 6-month prior to the Screening visit or significant risk of suicide. Any condition that in the opinion of the investigator makes the subject unsuitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vafidemstat 1.2mg<br>Vafidemstat is administered as capsules. | Drug: vafidemstat<br>* 1.2mg capsule<br>* Other names: ORY-2001;|
| Placebo Comparator: placebo<br>Placebo is administered as capsules. | Drug: Placebo<br>* placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) | Evaluation of the difference on the Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) from baseline to specific week, between the active treatment arm and the placebo arm | From baseline up to week 14 | 
| Efficacy: Borderline Personality Disorder Checklist (BPDCL) | Evaluation of the difference on the Borderline Personality Disorder Checklist (BPDCL), from baseline to specific week, between the active treatment arm and the placebo arm | From baseline up to week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Clinical Global Impression-Severity focused on Agitation/Aggression (CGI-S A/A) | Evaluation of the change over time on the CGI-S A/A | Change up to week 14 | 
| Efficacy: Borderline Personality Disorder Checklist (BPDCL) | Evaluation of the change over time on the BPDCL | Change up to week 14 | 
| Efficacy: Borderline Evaluation of Severity over Time (BEST) | Evaluation of the difference on BEST between the active treatment arm and the placebo arm | Change up to week 14 and from baseline to week 14 | 
| Efficacy: Beck Depression Inventory II (BDI-II) | Evaluation of the difference on BDI-II between the active treatment arm and the placebo arm | Change up to week 14 and from baseline to week 14 | 
| Efficacy: State-Trait Anger Expression Inventory 2 (STAXI-2) | Evaluation of the difference on STAXI-2 between the active treatment arm and the placebo arm | Change up to week 14 and from baseline to week 14 | 
| Efficacy: State-Trait Anxiety Inventory (STAI) | Evaluation of the difference on STAI between the active treatment arm and the placebo arm | Change up to week 14 and from baseline to week 14 | 
| Safety - Adverse events | Treatment emergent adverse events | From baseline to week 14 | 
| Safety - Withdrawn patients | Percentage of withdrawn patients | From baseline to week 14 | 
| Safety endpoints - Columbia-Suicide Severity Rating Scale (C-SSRS). | Columbia-Suicide Severity Rating Scale (C-SSRS) | From baseline to week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Borderline personality disorder, vafidemstat