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?

This trial explores whether ocrelizumab, an immunotherapy drug, can help treat psychosis, which includes symptoms like hallucinations and unusual thoughts. Researchers believe that some individuals with schizophrenia or bipolar disorder might have a brain issue caused by their immune system mistakenly attacking the brain. The trial will compare ocrelizumab to a placebo (a treatment that looks real but isn’t) to determine if it reduces these symptoms. Individuals who have experienced psychotic symptoms for at least six months and had no psychiatric issues before age 15 might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ocrelizumab, the treatment being tested, is generally safe. In earlier studies for conditions like multiple sclerosis, some participants who took ocrelizumab experienced infections, but this was similar to those who took a placebo (a harmless pill with no active medicine). This suggests the treatment does not significantly increase the risk of infections. Importantly, the FDA has already approved ocrelizumab for treating other diseases, providing some confidence about its safety. However, individual reactions can vary, so discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for psychosis?

Ocrelizumab is unique because it targets CD20-positive B cells, which are thought to play a role in the development of psychosis. This mechanism is different from the dopamine and serotonin pathways targeted by most current antipsychotic medications. Researchers are excited about ocrelizumab because it offers a new approach by potentially modulating the immune system, which could lead to improved outcomes for patients who do not respond well to existing treatments. Additionally, its administration via intravenous infusion may provide a more controlled delivery compared to oral medications.

What evidence suggests that Ocrelizumab might be an effective treatment for psychosis?

Research has shown that ocrelizumab can help control the immune system, potentially benefiting conditions caused by the body's own antibodies. This treatment targets and reduces certain immune cells that might mistakenly attack the brain. In this trial, participants will receive either ocrelizumab or a placebo to evaluate its effectiveness in reducing symptoms like hallucinations in some people with schizophrenia or bipolar disorder. Other studies have demonstrated that ocrelizumab reduces relapse activity by 97%, effectively preventing symptoms from returning. While primarily studied in conditions like multiple sclerosis, its ability to manage immune responses suggests it might help if psychosis is linked to these antibodies. ^{1 3 6 7 8}

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.

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

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

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 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, 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]

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 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]

Citations

1. gene.com gene.com/media/press-releases/15078/2025-09-23/genentech-presents-new-data-for-ocrevus-

Genentech: Press Releases | Tuesday, Sep 23, 2025 Ocrevus shows 30% reduction in the risk of time to onset of 12-week composite confirmed disability progression (cCDP) in adults with advanced ...

2. ocrevus-hcp.com ocrevus-hcp.com/ocrevus-zunovo/efficacy.html

OCREVUS ZUNOVO® (ocrelizumab & hyaluronidase-ocsq) Learn about efficacy outcomes in OCREVUS ZUNOVO® (ocrelizumab and hyaluronidase-ocsq) clinical trials. See full safety for more information.

3. roche.com roche.com/media/releases/med-cor-2024-09-16

FDA approves OCREVUS ZUNOVO™ as the first and only ... Out of the exploratory outcomes measured, OCREVUS ZUNOVO was consistent with IV, demonstrating suppression of relapse activity (97%) and MRI ...

4. roche.com roche.com/investors/updates/inv-update-2025-04-02b

Roche provides update on Phase III OCREVUS high dose ... The rates of disability progression were low and consistent with rates observed in the previous pivotal studies of OCREVUS IV 600 mg. In ...

5. gene.com gene.com/media/press-releases/15036/2024-09-13/fda-approves-ocrevus-zunovo-as-the-first

FDA Approves Ocrevus Zunovo™ as the First and Only ... Out of the exploratory outcomes measured, Ocrevus Zunovo was consistent with IV, demonstrating suppression of relapse activity (97%) and MRI ...

6. ocrevus-hcp.com ocrevus-hcp.com/ocrevus-zunovo/safety.html

Safety | OCREVUS ZUNOVO® (ocrelizumab & hyaluronidase ... In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS was not associated with an ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761371s000lbl.pdf

Ocrevus Zunovo - accessdata.fda.gov The safety of ocrelizumab has been evaluated in active-controlled clinical trials of ocrelizumab administered intravenously in patients with relapsing forms ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8264886/

Clinical outcomes of patients with multiple sclerosis treated ... Phase III trials showed ocrelizumab significantly reduced risk of relapse recurrence, 3 and 6 months sustained disability progression, gadolinium-enhancing (Gd ...