Ocrelizumab for Psychosis by Autoimmunity (OPA)

The Methodist Hospital Research Institute (TMHRI)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Schizophrenia; Schizo-Affective Type of Psychosis

Treatments: Behavioral: Physical and neuro-cognitive evaluations; Biological: Ocrelizumab infusion; Behavioral: Psychosis and cognitive assessments; Diagnostic Test: Safety labs and electrocardiogram

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03971487

Pro00021901

Details and patient eligibility

About

Some people who have what doctors currently call schizophrenia or bipolar disease may actually have a brain disease caused by auto-antibodies. Auto-antibodies are produced when the normal defense mechanism of the body goes wrong and begins to attack the body, similar to "friendly fire." Auto-antibodies attack brain receptors and then the person who has this problem begins to have hallucinations and other manifestations of schizophrenia, like feeling that people can see what they are thinking and also feeling that other people do not like them. If this disease is caused by auto-antibodies, typically the person is well until they are 15 years of age or older, but seldom older than 35 years. Then, in a matter of a few months they begin to have hallucinations and the other symptoms. Doctors still do not know whether some people with schizophrenia or bipolar disease have auto-antibodies attacking their brain. For this reason, in this study some of these patients will receive a treatment that suppresses the auto-antibodies and their symptoms after treatment will be compared with the symptoms of a group of similar patients who are given a preparation that looks like the real treatment, but it is not.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals of either sex, 18-35 years of age.
• Having an active psychotic disorder meeting DSM-5 criteria, including a duration of at least six months, for Schizophrenia Spectrum Disorder, as defined by the Mini International Neuropsychiatric Interview (MINI).
• A total PANSS ≥ 60 and a score ≥ 4 on at least 2 of the PANSS positive symptoms.
• Normal academic performance at least until the age of 15 years and absence of psychiatric symptoms before the same age.
• Ability to assent or consent to the performance of the study and participate in testing procedures.

Exclusion criteria

• The dose of antipsychotic medication (if they are on one) has been changed less than two weeks prior to baseline PANSS testing (Visit 2, see below).
• Patient treated with a medication designed to suppress the immune system, other than standard analgesics or antipyretics, in the six months prior to randomization.
• Vaccinated with a live-attenuated vaccine less than 4 weeks before ocrelizumab infusion or with a non-live vaccine less than 2 weeks before infusion.
• Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus, syphilis, tuberculosis, PML).
• History of brain tumor, stroke, severe head trauma or multiple sclerosis.
• Active cancer, metabolic encephalopathy, severe cardiovascular or renal disease.
• In the judgment of the PI, psychosis related to substance abuse or metabolic disorders.
• Pregnancy or lactation.
• Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
• History of or currently active primary or secondary immunodeficiency.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Contraindications to or intolerance of oral or IV corticosteroids.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Ocrelizumab

Active Comparator group

Description:

Two doses of 300 mg of ocrelizumab will be administered as an intravenous infusion two weeks apart.

Treatment:

Behavioral: Psychosis and cognitive assessments

Diagnostic Test: Safety labs and electrocardiogram

Biological: Ocrelizumab infusion

Behavioral: Physical and neuro-cognitive evaluations

Placebo

Placebo Comparator group

Description:

Two placebo intravenous infusions will be administered two weeks apart.

Treatment:

Behavioral: Psychosis and cognitive assessments

Diagnostic Test: Safety labs and electrocardiogram

Behavioral: Physical and neuro-cognitive evaluations