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Cited by 5Posttraumatic Stress Disorder ResearchNicotinic Acetylcholine Receptors StudyVagus Nerve Stimulation Research

BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder

Papapetropoulos, Spyridon, Doolin, Elizabeth, O’Connor, Susan, Paul, Dharam, Odontiadis, Michael, Jaros, Mark, Rolan, Paul, Stein, Murray B.·2025·NEJM Evidence
DOI 10.1056/evidoa2400380
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Abstract

BACKGROUND: Post-traumatic stress disorder (PTSD) is a serious, debilitating, and prevalent psychiatric condition occurring in people who are traumatized and experience intense, disturbing thoughts and feelings that persist. BNC210 is a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator developed to treat PTSD. METHODS: , Fifth Edition) (CAPS-5) total symptom severity score of 30 or more were eligible (range: 0 to 80; in all scales used in this trial a higher score indicates a more severe condition). We randomly assigned patients 1:1 to a BNC210 dose of 900 mg twice daily or placebo for 12 weeks. The primary end point was a change from baseline to week 12 in CAPS-5 total score for BNC210 versus placebo. RESULTS: In the modified intent-to-treat population (n=182), an improvement in the CAPS-5 total score was observed with BNC210 compared with placebo (least squares [LS] mean difference: -4.03; Cohen's d effect size: 0.40; P=0.048) at week 12. A LS mean difference in CAPS-5 score of -4.11 was observed as early as week 4. The LS mean difference to week 12 for depressive symptoms measured on the Montgomery-Åsberg Depression Rating Scale (range: 0 to 60; minimal clinically important difference [MCID] ≥2]) was -3.19 and for sleep measured on the Insomnia Severity Index (range: 0 to 28; MCID 6) was -2.19. Treatment-emergent adverse events (AEs) occurred in 70 (66.7%) patients in the BNC210 group and 56 (53.8%) in the placebo group, most commonly headache, nausea, fatigue, and hepatic enzyme elevations. In the BNC210 treatment group, 21 patients withdrew from treatment for AEs, while 10 did so in the placebo group. There were no serious AEs or deaths reported for the BNC210 group. CONCLUSIONS: BNC210 improved PTSD symptom severity at week 12 with indications of effect as early as week 4. Our trial establishes equipoise for additional larger trials that are needed to determine the clinical utility of BNC210 for the treatment of PTSD. (Funded by Bionomics Limited; ClinicalTrials.gov number, NCT04951076.).

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Authors
Papapetropoulos, S., Doolin, E., O’Connor, S., Paul, D., Odontiadis, M., Jaros, M., Rolan, P., & Stein, M. B.
Affiliations
  • Bionomics (Australia) (AU)
  • Bionomics Limited, Adelaide, SA, Australia
  • Summit Analytical, Denver
  • The University of Adelaide (AU)
  • University of California San Diego (US)
ORCID
Venue
NEJM Evidence
Publisher
Massachusetts Medical Society
Published
2025-01
Volume
4
Issue
1
Pages
EVIDoa2400380-EVIDoa2400380
ISSN
2766-5526 (ISSN-L)
DOI
10.1056/evidoa2400380
OpenAlex
W4405152262
Cited by
5
References
39
Citations by year
2026: 1 · 2025: 3 · 2024: 1
FWCI
2.52
Type
journal article
Language
en
Open access
closed
Locations
  • NEJM Evidence (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
post-traumatic stress disorder, alpha7 nicotinic acetylcholine receptor, negative allosteric modulators, CAPS-5, depressive symptoms, insomnia, treatment-emergent adverse events, hepatic enzyme elevation, PTSD pharmacotherapy, sleep disorders
MeSH terms
Adolescent, Adult, Aged, Double-Blind Method, Female, Humans, Isoxazoles, Male, Middle Aged, Phenylurea Compounds, Stress Disorders, Post-Traumatic, Young Adult, alpha7 Nicotinic Acetylcholine Receptor

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