Ocrelizumab for Psychosis by Autoimmunity (OPA)

Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizo-Affective Type of Psychosis
• Intervention / Treatment: Behavioral: Psychosis and cognitive assessments; Behavioral: Physical and neuro-cognitive evaluations; Diagnostic test: Safety labs and electrocardiogram; Biological: Ocrelizumab infusion

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Joseph C Masdeu, MD, PhD; Phone Number: 202-255-7899; Email: jcmasdeu@houstonmethodist.org
• Study Contact Backup: Name: Haroon Shahid, MD; Phone Number: 713-441-1150; Email: mhshahid@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Research Institute
      • Principal Investigator: Joseph C Masdeu, MD, PhD
      • Contact: Nilene M Crisci, RN; Phone Number: 281-222-1782; Email: ncrisci@houstonmethodist.org
      • Contact: Maushami Gurung, CCRP; Phone Number: 713-441-4889; Email: mgurung@houstonmethodist.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ocrelizumab; Two doses of 300 mg of ocrelizumab will be administered as an intravenous infusion two weeks apart.	Behavioral: Psychosis and cognitive assessments; Administration of MINI, PANSS and Quality of Living scales; Behavioral: Physical and neuro-cognitive evaluations; Physical, neurological and cognitive evaluations.; Diagnostic test: Safety labs and electrocardiogram; Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.; Biological: Ocrelizumab infusion; Two IV infusions of 300 mg of ocrelizumab 2 weeks apart
Placebo Comparator: Placebo; Two placebo intravenous infusions will be administered two weeks apart.	Behavioral: Psychosis and cognitive assessments; Administration of MINI, PANSS and Quality of Living scales; Behavioral: Physical and neuro-cognitive evaluations; Physical, neurological and cognitive evaluations.; Diagnostic test: Safety labs and electrocardiogram; Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on the Positive and Negative Syndrome Scale (PANSS)	It measures symptoms of psychosis	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on quality of life scales for psychiatric patients	(modified to include input by caregivers)	Six months
Score on NIH Cognitive Toolbox	Tablet-implemented tool testing cognitive abilities, including working memory	Six months
Antipsychotic-equivalent medication ordered by patient's psychiatrist	Dose of medications for psychosis transformed to a standard equivalent	Six months

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Joseph C Masdeu, MD, PhD, Houston Methodist Neurological Institute

Publications and helpful links

General Publications

• Masdeu JC, Dalmau J, Berman KF. NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis? Trends Neurosci. 2016 May;39(5):300-310. doi: 10.1016/j.tins.2016.02.006. Epub 2016 Apr 26.
• Masdeu JC. Detecting synaptic autoantibodies in psychoses: need for more sensitive methods. Curr Opin Neurol. 2017 Jun;30(3):317-326. doi: 10.1097/WCO.0000000000000447.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): October 30, 2028

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; schizo-affective psychosis
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Psychotic Disorders; Investigative Techniques; Therapeutics; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Cardiovascular; Behavior Control; Immobilization; Heart Function Tests; Electrodiagnosis; Restraint, Physical; Electrocardiography
• Other Study ID Numbers: Pro00021901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is possible that anonymized data could be shared with other researchers at the conclusion of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes