Ocrelizumab for Multiple Sclerosis

(AMS05 Trial)

Recruiting at 15 trial locations

Overseen By Andrew Goodman

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: OCR

Must not be taking: Fingolimod, Cladribine, Natalizumab, others

Disqualifiers: PPMS, SPMS, PRMS, others

Prior Safety Data This treatment has passed at least one previous human trial

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: 12

123 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if patients with early relapsing multiple sclerosis can stop taking Ocrelizumab after initial treatment without their disease getting worse. Ocrelizumab is a medication given through an IV that helps manage multiple sclerosis by reducing harmful immune cells. The study will monitor patients for new disease activity over several years.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain treatments like systemic corticosteroids and some MS therapies are not allowed before the trial starts. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Ocrelizumab for treating multiple sclerosis?

Ocrelizumab has been shown to significantly reduce relapse rates in relapsing multiple sclerosis and slow disability progression in primary progressive multiple sclerosis, as demonstrated in clinical trials. It is more effective than interferon beta-1a and offers a convenient treatment schedule with infusions every six months. ^{1 2 3 4 5}

Is ocrelizumab safe for humans?

Ocrelizumab, also known as Ocrevus, has been studied for its safety in treating multiple sclerosis. Clinical trials and real-world studies have evaluated its safety profile, showing that it is generally safe for humans, although like any medication, it may have some side effects. ^{1 6 7 8 9}

What makes the drug Ocrelizumab unique for treating multiple sclerosis?

Ocrelizumab is unique because it is the first drug approved for early primary progressive multiple sclerosis and relapsing forms of multiple sclerosis, working by targeting and depleting B cells, which are involved in the disease. It offers a convenient treatment schedule with infusions every six months, and it has shown to be more effective than some existing treatments like interferon in reducing relapse rates and disease progression. ^{1 2 4 5 7}

Research Team

Amit Bar-Or, M.D.

Principal Investigator

University of Pennsylvania, Perelman School of Medicine: Department of Neurology

Eligibility Criteria

This trial is for adults with early Relapsing Multiple Sclerosis (RMS) diagnosed within the last 2 years. Participants must be willing to use effective contraception and have received an FDA-authorized COVID-19 vaccine. Exclusions include pregnancy, certain heart conditions, substance abuse, recent steroid therapy or live vaccines, metal implants affecting MRI scans, other significant diseases or infections like HIV or hepatitis.

Inclusion Criteria

I have had symptoms or an episode of MS within the last 2 years that meets specific criteria.

For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use effective methods of contraception during the treatment period and for at least 6 months after the last dose of study drug

My disease symptoms started less than 2 years ago.

Exclusion Criteria

Known presence or history of other neurological disorders, including but not limited to specific conditions

Pregnancy or lactation

Inability or unwillingness of a participant to give written informed consent or comply with study protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 or more visits (in-person)

Open-label Treatment

Participants receive OCR infusions at Days 0 and 14, followed by 600 mg infusions at Month 6, 12, 18, and 24

24 months

6 visits (in-person)

Blinded Treatment

Participants are randomized to receive either placebo or OCR infusions every 6 months

24 months

4 visits (in-person)

Unblinded Follow-up

Participants who discontinue blinded therapy before Month 48 may choose to receive OCR or other treatment and continue with study assessments

Up to 6 months

Safety Follow-up

Participants have a phone visit 6 months after their last dose to monitor safety

6 months

1 visit (phone)

Treatment Details

Interventions

• Ocrelizumab
• Placebo for Ocrelizumab

Trial Overview The study tests if it's safe and effective to stop Ocrelizumab (OCR) after initial treatment in RMS patients. It starts with standard OCR doses for a year; then participants are randomly assigned to continue OCR, switch from OCR to placebo at different intervals, or receive placebos only for up to four years.

Participant Groups

Group I: Ocrelizumab Arm Experimental Treatment 1 Intervention

All eligible participants will be initiated on OCR using the standard approved administration schedule of two 300 mg infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600 mg infusions at Month 6, 12, 18, and 24. In this arm participants will continue to receive OCR infusions every 6 months through Month 48.

Group II: Placebo Arm Placebo Group 1 Intervention

All eligible participants will be initiated on OCR using the standard approved administration schedule of two 300 mg infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600 mg infusions at Month 6, 12, 18, and 24. In this arm, starting at Month 30, participants will receive placebo infusions every 6 months through Month 48.

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?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

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

Autoimmunity Centers of Excellence (ACE)

Collaborator

Trials

2

Recruited

140+

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

44

Recruited

15,000+

Findings from Research

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 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, an anti-CD20 monoclonal antibody, is effective in reducing disability progression in primary progressive multiple sclerosis, but it can lead to severe late-onset neutropenia as a rare side effect.

In a reported case, a 34-year-old male developed severe neutropenia 42 days after receiving ocrelizumab, requiring hospitalization and treatment, highlighting the need for patient awareness and monitoring for symptoms like fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. Baird-Gunning, J., Yun, J., Stevenson, W., et al.[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, a monoclonal antibody used for treating multiple sclerosis, can be associated with the development of alopecia areata, as observed in five patients (two females and three males).

All patients responded positively to conventional treatments for alopecia areata, such as corticosteroids and minoxidil, indicating that this side effect is potentially reversible with appropriate care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab-induced alopecia areata-A series of five patients from Ontario, Canada: A case report. Chin, LD., AbuHilal, M.[2022]

In a review of 78 studies involving 4498 patients, 61.3% of those treated with ocrelizumab experienced adverse events, with the most common being infections (39.2%) and infusion-related reactions (26.2%).

Ocrelizumab was associated with a higher risk of infections compared to beta-interferon, particularly herpes-related and respiratory infections, while the risk of serious adverse events was similar between ocrelizumab and comparator groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. Ng, HS., Rosenbult, CL., Tremlett, H.[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 the first approved treatment for both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS), demonstrating significant efficacy in slowing disability progression in PPMS patients at 12 and 24 weeks.

The safety profile of ocrelizumab aligns with findings from clinical trials, showing no unexpected safety concerns, which supports its use in managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. Juanatey, A., Blanco-Garcia, L., Tellez, N.[2019]

In a study of 1104 multiple sclerosis patients treated with ocrelizumab over a median follow-up of 1.3 years, 94.5% were free of MRI activity, indicating strong effectiveness in stabilizing the disease.

Ocrelizumab was generally well tolerated, with only 10% of patients reporting side effects, primarily infusion-related reactions and infections, aligning with safety profiles observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. Pontieri, L., Blinkenberg, M., Bramow, S., et al.[2022]

References

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

Ocrelizumab: First Global Approval. [2022]

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

Ocrelizumab: A Review in Multiple Sclerosis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. [2022]

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

Ocrelizumab: A Review in Multiple Sclerosis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab-induced alopecia areata-A series of five patients from Ontario, Canada: A case report. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. [2022]