Ocrelizumab for Early Multiple Sclerosis

(IMPACT MS Trial)

Overseen By Naomi Okinishi, BS MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Disqualifiers: Pregnancy, Progressive MS, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment favorably alters CSF markers of chronic inflammation.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken any MS disease-modifying therapy before, and you must not have used corticosteroids within 7 days of the first ocrelizumab treatment.

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

Ocrelizumab has been shown to significantly reduce relapse rates and slow disease progression in patients with relapsing and primary progressive multiple sclerosis, as demonstrated in clinical trials like OPERA I and II and ORATORIO. 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 approved for treating multiple sclerosis and has undergone safety evaluations. Clinical trials and reviews have assessed its safety, noting that it can cause some adverse events (unwanted side effects), but it is generally considered safe for use in humans with multiple sclerosis. ^{1 6 7 8 9}

How is the drug Ocrelizumab unique for treating early multiple sclerosis?

Ocrelizumab (Ocrevus) is unique because it specifically targets and depletes B cells, a type of immune cell involved in the progression of multiple sclerosis, which helps reduce inflammation and slow disease progression. It is administered as an intravenous infusion, which is different from some other treatments that may be taken orally or through other routes. ^{10 11 12 13 14}

Research Team

Bruce Cree, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults aged 18-50 newly diagnosed with relapsing MS or high-risk CIS, who haven't received any MS treatments and can start treatment within 90 days of their first symptoms. Participants must not be pregnant, planning pregnancy, or breastfeeding and agree to effective contraception.

Inclusion Criteria

I had my first MS-like symptoms and an MRI showing inactive lesions within the last 90 days.

I agree to use effective birth control or remain abstinent during and after the study.

Signed Consent Form

Exclusion Criteria

I have not been treated for latent or active tuberculosis.

You currently have a hepatitis C virus infection.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 90 days

Initial Treatment

Participants receive ocrelizumab (300 mg IV x 2 doses given 2 weeks apart) at disease origin

2 weeks

Maintenance Treatment

Participants receive maintenance ocrelizumab 600 mg every 6 months

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Ocrelizumab

Trial Overview The study tests whether Ocrelizumab given at the onset of MS alters markers in cerebrospinal fluid that indicate chronic inflammation. It's aimed at understanding early intervention impacts on disease progression.

Participant Groups

Group I: Observational study cohort Active Control 1 Intervention

Subjects enrolled into an observational study matched for the same disease duration and who are either untreated or treated with alternate MS disease modifying therapies will serve as a parallel reference group

Group II: Ocrelizumab treated Active Control 1 Intervention

Participants age 18-50 with a first clinical presentation of MS or high-risk CIS diagnosed within 90 days of screening will be treated with ocrelizumab (300 mg IV x 2 doses given 2 weeks apart) at disease origin and with maintenance ocrelizumab 600 mg every 6 months through 30 months with a final study visit at 3 years

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Valhalla Foundation

Collaborator

Trials

1

Recruited

30+

Valhalla Foundation

Collaborator

Trials

2

Recruited

1,200+

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

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 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]

In a post hoc analysis of pivotal trials, ocrelizumab significantly reduced the risk of confirmed disability progression in multiple sclerosis patients with higher baseline disability (Expanded Disability Status Scale scores ≥4.0).

The analysis included patients from the OPERA trials (relapsing MS) and ORATORIO trial (primary progressive MS), showing that ocrelizumab was more effective than interferon β-1a and placebo in slowing disability progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. Wolinsky, JS., Engmann, NJ., Pei, J., et al.[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]

Niraparib (Zejula) is effective for treating recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, providing a targeted therapy option for these specific cancer types.

Ocrelizumab (Ocrevus) has shown efficacy in managing both relapsing and primary progressive multiple sclerosis, while dupilumab (Dupixent) is effective for patients with moderate-to-severe atopic dermatitis, highlighting its role in managing chronic inflammatory skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

The study is investigating the efficacy of Olvimulogene nanivacirepvec (Olvi-Vec) combined with platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer, aiming to improve progression-free survival (PFS).

This phase III trial will enroll approximately 186 patients and compare the experimental treatment to standard chemotherapy, with results expected to be presented in 2025, addressing a critical need for more effective therapies in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer. Holloway, RW., Thaker, P., Mendivil, AA., et al.[2023]

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

Ocrelizumab: A Review in Multiple Sclerosis. [2023]

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

Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension. [2021]

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

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. [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]

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

Pharmaceutical Approval Update. [2020]

11. England pubmed.ncbi.nlm.nih.gov

A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer. [2021]

12. England pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer. [2023]

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

Profiling the immune landscape in mucinous ovarian carcinoma. [2023]

14. England pubmed.ncbi.nlm.nih.gov

APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis. [2023]