Randomized, Blinded Discontinuation Trial of Ocrelizumab in Early Relapsing Multiple Sclerosis (AMS05)

Plain English Summary

Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis is a Phase 4 clinical trial sponsored by National Institute of Allergy and Infectious Diseases (NIAID) studying Multiple Sclerosis. This study tests if stopping Ocrelizumab (a medication for MS) after 2 years is safe and effective for people with early relapsing MS. It is for individuals diagnosed with early relapsing multiple sclerosis (MS) within the last 3 years. Participants will receive Ocrelizumab for 2 years, then be randomly assigned to continue Ocrelizumab or receive a placebo for another 2 years. Alternative treatments for early MS include other disease-modifying therapies that are taken continuously. The trial aims to enroll 123 participants.

Official Summary

This study is a prospective, multi-center, randomized, double blinded, placebo-controlled study of OCR treatment-discontinuation in patients with early RMS. 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. At Month 24, participants will be randomized (2:1) to one of two Arms with randomized treatment beginning at Month 30: Arm 1: placebo infusions every 6 months; or Arm 2: OCR infusions every 6 months. The treatment period will be for a total of 48 months.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have been diagnosed with early relapsing MS within the last 3 years and meet specific criteria. You cannot join if you have a different form of MS (like progressive MS), have certain medical conditions, or have implants that prevent MRI scans. Participants must be able to provide informed consent and comply with the study schedule. Women of childbearing potential must agree to use effective contraception. This trial is studying Multiple Sclerosis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures whether patients experience a clinical relapse (a new or worsening MS symptom) between months 24 and 48, indicating if stopping the drug leads to disease activity. The specific primary outcome measures are: Absence of clinical relapse (From Month 24 to Month 48). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This is a Phase 4 (post-marketing) study of a treatment that has already received FDA approval. Phase 4 trials monitor long-term safety, effectiveness in broader patient populations, and potential interactions with other treatments in real-world settings. These studies can involve thousands of patients and help identify rare side effects that may not have appeared in earlier, smaller trials.

Why This Trial Matters

This trial is important because it aims to understand if patients with early relapsing MS can safely stop Ocrelizumab after an initial treatment period, potentially reducing long-term medication expos This research targets Multiple Sclerosis, where improved treatment options are needed.

Investor Insight

This trial investigates a common treatment for MS, suggesting a potential shift in treatment paradigms if discontinuation proves viable, impacting a significant market for MS therapies. This treatment is already approved and on the market. This post-marketing study monitors real-world outcomes.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of stopping Ocrelizumab versus continuing it. Understand that you will receive infusions every 6 months for the first 2 years, and then be randomly assigned to receive either Ocrelizumab or a placebo for the next 2 years. Be prepared for regular study visits, MRI scans, and blood tests throughout the 4-year study period. This trial is currently recruiting participants. The trial is being conducted at 12 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 123 participants

Interventions

• DRUG: Ocrelizumab — Two 300 mg intravenous (IV) OCR infusions separated by 14 days (i.e., Days 0 and 14) for a total of 600 mg, followed by 600 mg OCR infusions every 6 months from Month 6 through Month 48.
• DRUG: Placebo for Ocrelizumab — Placebo infusions every 6 months from Month 30 through Month 48.

Primary Outcomes

• Absence of clinical relapse (From Month 24 to Month 48)

Secondary Outcomes

• The change in Expanded Disability Status Scale (EDSS) score (Month 24 to Month 48)
• Proportion of participants with a serious adverse event (SAE) (Month 0 to Month 48)
• Proportion of participants who experience at least one Grade 3 or higher adverse event (Month 0 to Month 48)
• Proportion of participants with infections, Grade 3 or higher (Month 0 to Month 48)
• Proportion of participants with malignancies (Month 0 to Month 48)

Full Eligibility Criteria

Inclusion Criteria:

1. Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) with a dissemination in time that can be met clinically, by Magnetic Resonance Imaging (MRI), or based on oligoclonal band (OCB) positivity
2. Have a length of disease duration, from first symptom, of ≤ 3 years at time of informed consent
3. 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:

   1. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
   2. Examples of contraceptive methods include bilateral tubal ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices, and copper intrauterine devices
   3. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception
   4. Barrier methods must always be supplemented with the use of a spermicide

Exclusion Criteria:

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. History of primary progressive multiple sclerosis (PPMS), progressive relapsing multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)
3. Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI
4. Known presence or history of other neurological disorders, including but not limited to the following:

   * Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
   * CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, CNS sarcoidosis, or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments
5. Pregnancy or lactation

   • Female participants of childbearing potential must have a negative urine pregnancy test at screening
6. Any concomitant disease that may require chronic systemic treatment with corticosteroids or immunosuppressants during the course of the study
7. Lack of peripheral venous access
8. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
9. Significant, inadequately controlled (e.g., diagnostic evaluations indicated or change in medications warranted) disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that in the opinion of the investigator may preclude participant from participating in the study
10. Functional status of New York Heart Association (NYHA) Class III or higher for heart failure at the screening visit
11. Known active bacterial, viral, fungal, mycobacterial infection or other infection (including tuberculosis (TB) or atypical mycobacterial disease but excluding limited superficial fungal or viral infections of the skin or nails) or any severe episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to Mo 0/Day 0 infusion or oral antibiotics within 2 weeks prior to Mo 0/Day 0 infusion
12. Active or chronic infection with human immunodeficiency virus (HIV), syphilis or TB (see laboratory tests below)
13. Evidence of past hepatitis B (including treated hepatitis B) or untreated hepatitis C infection (treated hepatitis C is not considered exclusionary). Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection (see laboratory tests below).
14. Known active malignancy or active monitoring for recurrence of malignancy, including solid tumors and hematological malignancies, except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix or the uterus that have been excised with clear margins
15. Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home
16. Receipt of live or live-attenuated vaccines within 4 weeks prior to Mo 0/Day 0 infusion
17. Contraindications to or severe intolerance of oral or IV corticosteroids

Trial Locations

• Yale School of Medicine, New Haven, Connecticut, United States
• MedStar Georgetown University Hospital, Washington D.C., District of Columbia, United States
• Northwestern University, Chicago, Illinois, United States
• Massachusetts General Hospital, Boston, Massachusetts, United States
• University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, United States
• Icahn School of Medicine at Mount Sinai, New York, New York, United States
• University of Rochester Medical Center, Rochester, New York, United States
• Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
• University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States
• University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ...and 2 more locations

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis
• Relapsing-Remitting Multiple Sclerosis
• Early Multiple Sclerosis
• Neurological Disorders
• Autoimmune Diseases
• Inflammatory Diseases
• Central Nervous System Disorders
• Immunosuppression
• Monoclonal Antibody Therapy
• Neuroinflammation

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