LB-102 Phase 2 Trial in Acute Schizophrenia Shows Week 4 Benefit

Key Takeaways

• At week 4, LB-102 50 mg and 75 mg met the primary endpoint versus placebo, while 100 mg was significant on a nominal basis only.
• The trial used once-daily oral dosing in adults aged 18 to 55 years hospitalized for acute exacerbation of schizophrenia in a US multicenter double-blind placebo-controlled phase 2 study.
• Treatment-emergent adverse events, discontinuations due to adverse events, and serious adverse events were reported across groups, with one death occurring in the placebo arm.

The NOVA1 phase 2 trial was a US-based, multicenter, double-blind, placebo-controlled randomized clinical trial conducted from December 2023 to August 2024. It enrolled adults aged 18 to 55 years with schizophrenia who required hospitalization or continued hospitalization for an acute exacerbation of psychotic symptoms. Participants were randomized 3:3:3:1 to oral once-daily placebo or LB-102 50 mg, 75 mg, or 100 mg, with 359 patients included overall. The protocol included screening for up to 14 days, a 28-day inpatient treatment period, a 5-day inpatient stabilization period, and outpatient safety follow-up about 2 weeks after treatment ended. The prespecified primary endpoint was change from baseline to week 4 in PANSS total score, with Hochberg multiplicity correction applied to the 50 mg and 75 mg comparisons.

Baseline characteristics showed a mean age of 39.1 years, 80.8% male participation, and mean PANSS total scores of about 94 across groups. Week 4 PANSS total score changes were placebo -9.3 (SE 1.08); 50 mg -14.3 (SE 1.10), P < .001, Hedges g = 0.61; 75 mg -14.0 (SE 1.11), P = .002, Hedges g = 0.41; 100 mg -16.1 (SE 1.91), nominal P = .002, Hedges g = 0.83. The 50 mg and 75 mg doses were statistically superior after multiplicity control, whereas the 100 mg result was nominal only. Secondary endpoints listed in the abstract included CGI-S measures, PANSS subscales, PANSS Marder factors, and 20% or greater PANSS response. PANSS total score reductions were greater than placebo at all 3 doses, with multiplicity-controlled significance at 50 mg and 75 mg.

Treatment-emergent adverse events occurred in placebo 60 (56%), 50 mg 74 (69%), 75 mg 62 (57%), and 100 mg 27 (75%). Withdrawals due to treatment-emergent adverse events were placebo 2, 50 mg 2, 75 mg 3, and 100 mg 3. Five serious treatment-emergent adverse events were reported overall, with placebo 2, including 1 death, and 1 event in each LB-102 arm. The investigators concluded that the trial supported LB-102 efficacy and safety in adults with acute schizophrenia; the registration identifier was NCT06179108.