A randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulins and rituximab in patients with antibody-associated psychosis (SINAPPS2)

INTERVENTION: Trade Name: IVIG Product Name: IVIG Pharmaceutical Form: Solution for infusion INN or Proposed INN: Human normal immunoglobulin Concentration unit: g/ml gram(s)/millilitre Concentration type: equal Concentration number: 0.1‐ Pharmaceutical form of the placebo: Solution for infusion in administration system Route of administration of the placebo: Intravenous use Trade Name: Rituximab Product Name: Rituximab Pharmaceutical Form: Solution for infusion INN or Proposed INN: Rituximab Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Solution for infusion in administration system Route of administration of the placebo: Intravenous use CONDITION: Antibody associated Psychosis Therapeutic area: Psychiatry and Psychology [F] ‐ Mental Disorders [F03] PRIMARY OUTCOME: Main Objective: To test the efficacy of immunotherapy (IVIG and rituximab) in patients with acute psychosis associated with anti‐neuronal membranes. Primary end point(s): The primary outcome is time to start of remission, sustained for 6 months. Remission is defined as PANSS=3 on PANSS (Kay 1987) items P1, G9, P3, P2, G5, N1, N4, N6 for previous 6 months (Andreasen et al.2005). Secondary Objective: To test the safety of immunotherapy (IVIG and rituximab) of patients with acute psychosis associated with anti‐neuronal membranes. Timepoint(s) of evaluation of this end point: Month 3, 6, 9, 12 (15,18) SECONDARY OUTCOME: Secondary end point(s): The secondary outcomes are time to first treatment response (whether sustained or not) and relapse rate, and number of adverse effects, serious infections, proportion of patients reaching 20%, 30% and 40% reduction in PANSS total score and changes in the following clinical rating scales: CGI, YMRS, ANNSERS, BACS, GAF. Timepoint(s) of evaluation of this end point: Baseline to 12 months (up 18 months in some cases ‐ the few patients entering remission after month 6, for a further 6 months) INCLUSION CRITERIA: To be included in the trial the patient must have: • Patient or legal representative is willing and able to provide informed consent. • Acute psychosis for at least 2 weeks (defined as symptomatic on the PANSS scale by score equal to or greater than 4 on P1, G9, P3, P2, G5, N1, N4, N6). • This may either be a first episode or relapse after remission (remission defined as PANSS=3 on PANSS items P1, G9, P3, P2, G5, N1, N4, N6 for previous 6 months). • Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 78 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2