A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-Traumatic Stress Disorder (PTSD)

Phase 2

Completed

• Conditions: Post-Traumatic Stress Disorder
• Interventions: Drug: Placebo; Drug: BNC210

• Registration Number: NCT04951076
• Lead Sponsor: Bionomics Limited

Brief Summary

The purpose of this study is to assess the effects of BNC210 compared to placebo on Post-Traumatic Stress Disorder (PTSD) symptom severity as measured by the Clinician Administered PTSD scale for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) Total Symptom Severity Scores.

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel group, multi-center study with a 12 week, 2-arm treatment period. Participants will attend a Screening visit within 3 weeks before randomization to confirm eligibility. Approximately 200 participants will be randomized using a 1:1 ratio to receive either BNC210 900 mg twice daily (b.i.d.) or matched placebo. Participants will then complete 12 weeks of treatment with their allocated study intervention. Participants will return to their study site at 2-weekly intervals to complete study assessments. Participants are then requested to attend a Follow-up visit at Week 15 (i.e., 3 weeks after their last study intervention is administered).

Study Timeline

• Study First Submitted: 2021-06-27
• Study First Submitted QC: 2021-06-27
• Study First Posted: 2021-07-06
• Study Start: 2021-07-27
• Primary Completion: 2023-07-25
• Study Completion: 2023-08-14
• Status Verified: 2024-12
• Results First Submitted: 2024-12-17
• Results First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Results First Posted: 2025-02-06
• Last Update Posted: 2025-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

• Participants with a current diagnosis of PTSD as defined by the CAPS-5 for DSM-5, with a CAPS-5 Total Symptom Severity Score of ≥30 at Screening and Baseline and no >25% decrease in Score from Screening to Baseline
• The index trauma event must have occurred in adulthood, i.e., when the participant was ≥18 years of age
• Suitable contraception use in line with protocol requirements
• Ability to swallow tablets

Exclusion Criteria

• A period of less than 6 months since the index trauma event
• Current and ongoing exposure to the trauma that caused the PTSD
• Complex PTSD
• Severe depression as measured by a score of ≥ 35 on the Montgomery Asberg Depression Rating Scale (MADRS)
• Borderline personality disorder, bipolar disorder and other psychotic disorders
• Use of antidepressant medications within 30 days (fluoxetine within 90 days) of Screening. The use of alprazolam, flunitrazepam and chronic daily use of other benzodiazepines within 90 day of Screening.
• Failed more than three trials of antidepressant medication(s) prescribed for the treatment of PTSD.
• Concurrent trauma-based psychotherapy such as Cognitive Behavior Therapy, Prolonged Exposure Therapy, Eye Movement Desensitization and Reprocessing Therapy. Participants may however continue to receive supportive counseling that has been in place for a minimum of three months prior to Screening.
• Any moderate or severe substance use disorder in the past 12 months
• Any clinically significant medical history or findings as determined by the Investigator that could interfere with the objectives of the study or put the participant at risk

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
BNC210	BNC210	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline on the Clinician Administered Post-Traumatic Stress Disorder (PTSD) Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) Total Symptom Severity Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks,12 weeks	The CAPS-5 is a 30-item structured interview used to diagnose PTSD and assess PTSD symptoms over the past month. Information about the frequency and intensity of each item is combined into a severity rating, and the CAPS-5 total symptom severity score is calculated by adding the severity scores for the 20 PTSD symptoms in the DSM-5. Scores range from 0 to 80, with higher scores indicating greater severity of PTSD symptoms.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline on Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Criterion B Symptom Cluster Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	Criterion B (Intrusive Thoughts) is a 5-item sub section of the CAPS-5 scale that assesses intrusion symptoms associated with the traumatic event(s) of PTSD, with each item rated on a scale from 0 (not present) to 4 (extreme / incapacitating). Scores range from 0 to 20, with higher scores indicating greater severity of intrusion symptoms.
Change From Baseline on Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Criterion C Symptom Cluster Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	Criterion C (Avoidance) is a 2-item sub section of the CAPS-5 scale that assesses avoidance of stimuli associated with the traumatic event(s) of PTSD, with each item rated on a scale from 0 (not present) to 4 (extreme / incapacitating). Scores range from 0 to 8, with higher scores indicating greater severity of avoidance symptoms.
Change From Baseline on Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Criterion D Symptom Cluster Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	Criterion D (Negative Alterations in Cognitions and Mood) is a 7-item sub section of the CAPS-5 scale that assesses negative alterations in cognitions and mood associated with the traumatic event(s) of PTSD, with each item rated on a scale from 0 (not present) to 4 (extreme / incapacitating). Scores range from 0 to 28, with higher scores indicating greater severity of negative alterations in cognitions and mood symptoms.
Change From Baseline on Clinician Administered PTSD Scale for DSM-5 (CAPS-5) Criterion E Symptom Cluster Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	Criterion E (Arousal and Reactivity) is a 6-item sub section of the CAPS-5 scale that assesses marked alterations in arousal and reactivity associated with the traumatic event(s) of PTSD, with each item rated on a scale from 0 (not present) to 4 (extreme / incapacitating). Scores range from 0 to 24, with higher scores indicating greater severity of arousal and reactivity symptoms.
Change From Baseline on Montgomery Asberg Depression Rating Scale (MADRS) Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	The MADRS is a 10-item clinician-rated questionnaire to measure the presence and severity of depressive episodes. Each item is rated on a scale of 0 to 6. The score from each item is combined into a total score ranging from 0 to 60, with higher scores indicating greater severity of depressive episodes.
Change From Baseline on Hamilton Anxiety Rating Scale (HAM-A) Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	The HAM-A is an interview questionnaire that measures severity of anxiety symptoms based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints and behavior during the interview. Each parameter is rated on a scale of 0 (not present) to 4 (very severe). The score from each parameter is combined into a total score. Scores range from 0 to 56, with higher scores indicating greater severity of anxiety symptoms.
Change From Baseline on Clinician Global Impression - Severity (CGI-S) Scale Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	The CGI-S is a rating scale designed to assess the overall severity of the participant's symptoms. Severity is rated on a scale from 1 (normal, not at all ill) to 7 (among the most extremely ill of participants), with a higher score indicating greater severity of symptoms.
Change From Baseline on Patient Global Impression - Severity (PGI-S) Scale Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	Change from Baseline on patient-reported global functioning; The PGI-S is a patient self-reported counterpart of the CGI-S designed to assess the patient's impression of their perceived severity of overall symptoms.Severity is rated on the PGI-S from 1 (normal) to 6 (very severe), with a higher score indicating greater severity of symptoms.
Change From Baseline on Insomnia Severity Index (ISI) Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks, 12 weeks	The ISI is a brief self-report instrument measuring both nocturnal and diurnal symptoms of insomnia. The ISI comprises seven items, each scored from 0 to 4. The scores from each of the 7 questions are added up to get a total score of 0 to 28, with a higher score indicating a higher level of symptom severity.
Change From Baseline on Sheehan Disability Scale (SDS) Scores After 12 Weeks	Baseline, 4 weeks, 8 weeks,12 weeks	The SDS is a rating scale designed to measure impairment in three domains: work/school, social life, and family life/home responsibilities. Each item is rated on a scale of 0 (not at all) to 10 (extremely), for a total score of 0 to 30, with a higher score indicating a higher degree of impairment.
Change From Baseline on PTSD Checklist for DSM-5 (PCL-5) Scores After 12 Weeks	Baseline, 12 weeks	The PCL-5 is a 20-item self-report assessment of the 20 DSM-5 symptoms of PTSD. Each symptom is rated on a scale from 0 (not at all) to 4 (extremely). Scores range from 0 to 80, with higher scores indicating greater severity of PTSD symptoms.

Trial Locations

Locations (2)

ATTTUNE Study Clinical Trial Site; 🇺🇸 Jacksonville, Florida, United States

ATTUNE Study Clinical Trial Site; 🇬🇧 Stockton-on-Tees, United Kingdom