Phase 3 clinical development program of LB-102 in schizophrenia: A double-blind placebo-controlled trial (NOVA-2) and an open-label extension study (NOVA-3)

Introduction

Schizophrenia remains a high-burden psychiatric disorder in which available antipsychotics often provide incomplete benefit across symptom domains and are constrained by tolerability liabilities, including extrapyramidal symptoms, sedation, metabolic effects, and broader functional burden. LB-102 is an investigational novel benzamide D₂/D₃/5-HT₇ antagonist under development as a once-daily treatment for schizophrenia and other neuropsychiatric disorders. In the phase 2 NOVA-1 trial, LB-102 met the primary endpoint, demonstrating a statistically significant improvement from baseline in the Positive and Negative Syndrome Scale (PANSS) total score versus placebo at all evaluated doses after 4 weeks of inpatient treatment for a psychotic relapse. The NOVA-1 trial also showed that LB-102 was generally safe and well tolerated, with low rates of extrapyramidal symptoms, including akathisia, minimal sedation, and few gastrointestinal side effects. The phase 3 clinical development program for LB-102 in schizophrenia is designed to confirm LB-102’s efficacy in adults experiencing a psychotic relapse and to assess its long-term safety, tolerability, and effectiveness for the treatment of adults with stable schizophrenia.

Objectives

To describe the phase 3 clinical development program for LB-102 in schizophrenia, including a pivotal trial to further evaluate its efficacy and safety in patients experiencing a psychotic relapse (NOVA-2) and a 52-week open-label extension trial (NOVA-3) to evaluate its long-term safety and tolerability in patients with stable schizophrenia.

Methods

NOVA-2 (NCT07363577) is a pivotal phase 3, multicentre, randomised, double-blind, placebo-controlled, fixed-dose clinical trial in adults (18-65yrs) with schizophrenia experiencing a psychotic relapse. The ~456 planned participants will be randomised (1:1:1) to once-daily, oral LB-102 50 mg, LB-102 100 mg, or placebo for 6 weeks of inpatient treatment. Key inclusion criteria include a diagnosis of schizophrenia (DSM-5) and PANSS total score 80-120 at screening and baseline. The primary efficacy endpoint is the change from baseline to Week 6 in PANSS total score. Secondary efficacy endpoints include the Clinical Global Impressions–Severity of illness scale (CGI-S), PANSS Positive and Negative Subscales, PANSS Marder factor scores, a dedicated scale to measure cognitive performance, and Personal and Social Performance scale (PSP). LB-102 safety, tolerability, and pharmacokinetics will also be assessed.

NOVA-3 (NCT07369154) is a phase 3, 52-week, multicentre, open-label, flexible-dose (50 mg–100 mg) clinical trial designed to assess the long-term safety and tolerability of LB-102 for the treatment of adults with stable schizophrenia. Eligible participants are adults (18-65yr) with stable schizophrenia (PANSS total score ≤70 and CGI-S score ≤3 at screening) who are experiencing inadequate response or issues with side effects, general tolerability, or overall effectiveness of their current antipsychotic medication or who have completed their participation in NOVA-2. With ~900 participants estimated for enrolment, NOVA-3 will assess the 52-week safety and tolerability of LB-102 treatment, as well as its effectiveness (PANSS, CGI-S, cognitive performance, PSP) over 52 weeks of treatment.

Conclusions

The phase 3 NOVA-2 and NOVA-3 clinical trials represent a robust and scientifically rigorous late-stage development program to evaluate the potential multidimensional efficacy of LB-102 in adults with schizophrenia and its short- and long-term safety and tolerability profile.

References

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