Ocrelizumab for Psychosis

(OPA Trial)

Overseen By Joseph C Masdeu, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infection, Cancer, Severe cardiovascular, others

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but if you are on antipsychotic medication, the dose should not have changed less than two weeks before the baseline testing. Also, you cannot participate if you have been treated with immune-suppressing medication in the six months before the trial.

How does the drug Ocrelizumab differ from other treatments for psychosis?

Ocrelizumab is unique because it is a humanized monoclonal antibody that targets B cells, which is a different approach compared to typical psychosis treatments. It is administered as an infusion every six months, which is less frequent than many other medications. ^{1 2 3 4 5}

Who Is on the Research Team?

Joseph C Masdeu, MD, PhD

Principal Investigator

HOUSTON METHODIST NEUROLOGICAL INSTITUTE

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-35 who have been diagnosed with an active psychotic disorder, such as schizophrenia or schizoaffective disorder. They should have had normal academic performance until age 15 and no psychiatric symptoms before then. Participants must score a certain level on the PANSS, which measures psychosis severity.

Inclusion Criteria

I have been diagnosed with a long-term psychotic disorder.

I had normal school performance and no psychiatric symptoms until age 15.

A total PANSS ≥ 60 and a score ≥ 4 on at least 2 of the PANSS positive symptoms

Exclusion Criteria

I haven't had a live vaccine in the last 4 weeks or any vaccine in the last 2 weeks before my ocrelizumab infusion.

My antipsychotic medication dose hasn't changed in the last 2 weeks.

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of 300 mg of ocrelizumab or placebo as intravenous infusions two weeks apart

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Regular assessments (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ocrelizumab

Trial Overview The study tests Ocrelizumab, a drug that may suppress auto-antibodies causing brain disease leading to hallucinations and other psychosis symptoms. It includes physical evaluations, safety labs, ECGs, and cognitive assessments. Patients are compared to those receiving a placebo (a non-active treatment).

How Is the Trial Designed?

Group I: Ocrelizumab Active Control 4 Interventions

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

Group II: Placebo Placebo Group 3 Interventions

Two placebo intravenous infusions will be administered two weeks apart.

Ocrelizumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in European Union as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in Canada as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Ocrelizumab is a humanized anti-CD20 monoclonal antibody specifically designed to deplete B cells, which are implicated in the development of multiple sclerosis (MS).

Approved in March 2017 in the USA for treating both relapsing and primary progressive forms of MS, ocrelizumab represents a significant advancement in MS therapy, with its approval in the EU currently pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. Frampton, JE.[2022]

Ocrelizumab is the first drug approved by the European Medicines Agency for treating both early primary progressive multiple sclerosis and relapsing forms of multiple sclerosis, highlighting its significance in MS treatment.

The review discusses the safety and effectiveness of ocrelizumab, indicating it has undergone rigorous evaluation to support its use in adults with multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2018]

Ocrelizumab is an effective treatment for both relapsing forms of multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), showing significant reductions in relapse rates and disease progression over at least 7.5 years of treatment.

The drug is generally well tolerated, with no new safety concerns identified during long-term use, and offers the convenience of infusions every six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. Lamb, YN.[2023]

Ocrelizumab significantly reduces annualized relapse rates in adults with relapsing multiple sclerosis (RMS) compared to interferon β-1a, based on results from two 96-week trials.

In patients with primary progressive multiple sclerosis (PPMS), ocrelizumab significantly lowers the risk of confirmed disability progression over 120 weeks compared to placebo, and it is generally well tolerated with mostly mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. Syed, YY.[2022]

Ocrelizumab, a monoclonal antibody used to treat primary progressive multiple sclerosis, is associated with an increased risk of herpesvirus-related infections, particularly cytomegalovirus (CMV) infections.

While gastrointestinal side effects like inflammatory bowel disease (IBD) are rare with ocrelizumab, this case report highlights a complex situation where ocrelizumab-induced colitis overlapped with a CMV infection, complicating the management of the patient's multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab-induced colitis and cytomegalovirus infection and their disadvantageous interaction with underlying multiple sclerosis. Lieb, S., Heni, M., Rauschenberg, S., et al.[2023]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A Review in Multiple Sclerosis. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Ocrelizumab-induced colitis and cytomegalovirus infection and their disadvantageous interaction with underlying multiple sclerosis. [2023]