Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis

NCT05285891 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: DAIT AMS05
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Multiple Sclerosis

Keywords

Ocrelizumab; Multiple sclerosis; Relapse

Outcome Measures

Primary Outcomes (1)

• Absence of clinical relapse

  Durable remission of relapsing disease activity. This is defined as the absence of new relapsing disease activity from Month 24 through Month 48. This includes absence of clinical relapse as well as absence of evidence of MS disease activity by MRI defined by new or enlarging T2 lesions.

  From Month 24 to Month 48

Secondary Outcomes (7)

• 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

Study Arms (2)

Ocrelizumab Arm

EXPERIMENTAL

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.

Drug: Ocrelizumab

Placebo Arm

PLACEBO COMPARATOR

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.

Drug: Placebo for Ocrelizumab

Interventions

Ocrelizumab DRUG

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.

Also known as: Ocrevus

Ocrelizumab Arm

Placebo for Ocrelizumab DRUG

Placebo infusions every 6 months from Month 30 through Month 48.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Have a length of disease duration, from first symptom, of ≤ 3 years at time of informed consent
• 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:
• 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)
• Examples of contraceptive methods include bilateral tubal ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices, and copper intrauterine devices
• 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
• Barrier methods must always be supplemented with the use of a spermicide

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• History of primary progressive multiple sclerosis (PPMS), progressive relapsing multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI
• 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
• Pregnancy or lactation
• Female participants of childbearing potential must have a negative urine pregnancy test at screening
• Any concomitant disease that may require chronic systemic treatment with corticosteroids or immunosuppressants during the course of the study
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• 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
• Functional status of New York Heart Association (NYHA) Class III or higher for heart failure at the screening visit
• 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
• Active or chronic infection with human immunodeficiency virus (HIV), syphilis or TB (see laboratory tests below)

Sponsors & Collaborators

• Autoimmunity Centers of Excellence (ACE): collaborator
• Rho Federal Systems Division, Inc.: collaborator
• Genentech, Inc.: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10007, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14627, United States

RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The University of Texas Health Science Center at Houston, McGovern Medical School

Houston, Texas, 77030, United States

RECRUITING

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23298, United States

RECRUITING

Related Links

• Autoimmunity Centers of Excellence
• National Institute of Allergy and Infectious
• Division of Allergy, Immunology, and Transplantation

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Amit Bar-Or, M.D.

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

  STUDY CHAIR

Central Study Contacts

Amit Bar-Or

CONTACT

(215) 316-5151

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 18, 2022
• Study Start: January 12, 2023
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access

Locations

US (12)