IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2

University of Cambridge

Status and phase: Enrolling; Phase 2

Conditions: Psychosis; Autoimmune Encephalitis

Treatments: Drug: Rituximab; Drug: Placebo; Drug: Intravenous immunoglobulin

Study type: Interventional

Funder types: Other

Identifiers

NCT03194815

SINAPPS 2

Details and patient eligibility

About

A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel).

Primary objective: To test the efficacy of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.

Secondary objective: To test safety of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.

Full description

Investigators propose a randomised double-blinded placebo-controlled trial to test the hypothesis that immunotherapy is an effective treatment of antibody-associated psychosis, either first episode of psychosis or relapse following previous remission. Immunotherapy for the trial consists of one cycle of intravenous immunoglobulin (IVIG: 2g/kg over days 1-4) followed by two infusions of 1g rituximab (at day 28-35, and then 14 days after the first infusion). The rationale for this regime is that it combines a rapid-action treatment (IVIG) to induce remission with a longer-action therapy (rituximab) to maintain remission. It is based on a protocol where elimination of circulating antibodies is the treatment goal, namely "desensitisation" of potential transplant patients who have multiple anti-HLA antibodies capable of inducing hyperacute rejection and also being tested in various trials on clinicaltrials.gov (NCT00642655, NCT01178216, and NCT01502267). Blinding is required to minimise placebo responses in a trial based on symptomatology.

Enrollment: 70 estimated patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Acute psychosis >2 weeks. This may either be first episode or relapse after remission (remission defined as having mild or absent symptoms of psychosis for at least 6 months)
• Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
• Psychosis symptoms as defined by PANSS ≥4 on at least one of the following items: P1, P2, P3, N1, N4, N6, G5 and G9.

Exclusion criteria

• Current episode of psychosis greater than 24 months duration
• Co-existing severe neurological disease
• Evidence of current acute encephalopathy
• Hepatitis or HIV infection, pregnancy
• Contraindications to any trial drug
• Concurrent enrolment in another CTIMP

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

Intravenous immunoglobulin and Rituximab

Active Comparator group

Description:

One cycle of intravenous immunoglobulin (IVIG) 2g/kg over 2-5 days (days 1-5) followed by (b) two infusions of 1g rituximab (the first infusion starting between days 28-35, and the second infusion 14 days later), each with 100mg methylprednisolone.

Treatment:

Drug: Intravenous immunoglobulin

Drug: Rituximab

Placebo

Placebo Comparator group

Description:

One cycle of 0.9% saline solution over 2-5 days (days 1-5) followed by (b) two infusions of placebo solution alongside placebo pill - in equal volumes to steroid pre-medication and rituximab.

Treatment:

Drug: Placebo