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

Borderline Personality Disorder Clinical Trial

Official title:

"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)"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04932291
• Other study ID #: CL07-ORY-2001
• Status: Completed
• Phase: Phase 2
• Start date: March 26, 2021
• Est. completion date: November 13, 2023

Study information

• Verified date: September 2023
• Source: Oryzon Genomics S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: November 13, 2023
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Principal 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. 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.

5. Stable living environment for > 6 months before the Screening visit.

6. Body mass index (BMI) of at least 18.5 kg/m2, but no more than 35 kg/m2.

7. Willing and able to adhere to the prohibitions, restrictions and requirements specified in this protocol.

8. Otherwise, healthy, and medically stable based on medical history.

9. Clinical and neurological examinations and laboratory tests, as well as 12-lead ECG performed during screening that confirms subject is healthy and medically stable.

10. Able to read and write fluently and must have adequate hearing and visual acuity to complete the required testing outlined in this protocol.

11. 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.

12. 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.

13. 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])

14. Female subjects of childbearing potential must have a negative urine pregnancy test at screening and baseline.

15. Signed informed consent by participant prior to the initiation of any study specific procedure.

Principal exclusion criteria

1. DSM-5 diagnosis of intellectual disability, autism spectrum disorder, schizophrenia, schizoaffective disorder, bipolar disorder (or related disorders) or major depressive disorder (MDD) with psychosis.

2. Current DSM-5 diagnosis of conduct disorder, anorexia nervosa, bulimia nervosa, binge-eating disorder, oppositional defiant disorder, paranoid personality disorder or obsessive-compulsive disorder.

3. 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.

4. 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.

5. Use of illicit drugs for at least one week before Screening and subjects unwilling to abstain from use of these substances during the study.

6. 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.

7. 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.

8. Positive results for tuberculosis, Human Immunodeficiency Virus (HIV), Hepatitis C or Hepatitis B serology obtained at the Screening Visit.

9. Uncontrolled hypo- or hyperthyroidism at Screening Visit, based on laboratory parameters.

10. Clinically significant infection within the previous 30-days.

11. Chronic drug intake of specific forbidden medication

12. Esketamine in the past 90 days before the Screening visit.

13. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in the past 90 days before the screening visit.

14. Any regular intake of medications acting directly on central nervous system that investigator considers relevant to the study.

15. Member or immediate family of the study personnel or subordinate to any of the study personnel.

16. Enrollment in another investigational study or intake of investigational drug within the previous 3 months.

17. Suicide attempt within the 6-month prior to the Screening visit or significant risk of suicide.

18. Any condition that in the opinion of the investigator makes the subject unsuitable for inclusion in the study.

Related Conditions & MeSH terms

• Borderline Personality Disorder
• Personality Disorders

Intervention

Drug:
• vafidemstat
1.2mg capsule
• Placebo
placebo capsule

Locations

Country	Name	City	State
Bulgaria	Medical Center Hera EOOD - Psychiatry Office	Sofia	Sofia-Grad
Bulgaria	Medical Center Intermedika	Sofia	Sofia-Grad
Bulgaria	DCC "Mladost-M" Ltd, Psychiatr	Varna
Germany	Emovis GmbH	Berlin
Germany	Klinik fur Psychiatrie und Psychotherapie, LMU	München	Bayern
Serbia	Clinic for psychiatric disorders "Laza Lazarevic"	Belgrade
Serbia	Clinical center of Serbia	Belgrade
Serbia	Clinical center Kragujevac	Kragujevac
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
United States	Neurobehavioral Research Inc.	Cedarhurst	New York
United States	Center for Emotioal Fitness	Cherry Hill	New Jersey
United States	University of Chicago Institutional Review Board	Chicago	Illinois
United States	Revive Research Institute	Elgin	Illinois
United States	Core Clinical Research	Everett	Washington
United States	New Life Medical Research Center	Hialeah	Florida
United States	Phoenix Medical Research LLC	Miami	Florida
United States	The Medical Research Network	New York	New York
United States	Excell Research Inc	Oceanside	California
United States	Excell Research, Inc.	Oceanside	California
United States	Adams Clinical Trials, LLC	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Oryzon Genomics S.A.

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Efficacy: Borderline Personality Disorder Checklist (BPDCL)	Evaluation of the change over time on the BPDCL	Change up to week 14
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Safety - Adverse events	Treatment emergent adverse events	From baseline to week 14
Secondary	Safety - Withdrawn patients	Percentage of withdrawn patients	From baseline to week 14
Secondary	Safety endpoints - Columbia-Suicide Severity Rating Scale (C-SSRS).	Columbia-Suicide Severity Rating Scale (C-SSRS)	From baseline to week 14