Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis
NCT ID: NCT05285891
Last Updated: 2025-12-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE4
123 participants
INTERVENTIONAL
2023-01-12
2030-11-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The study will consist of the following periods, with participants undergoing study assessments, including physical exams, neurological exams, EDSS, LCLA, SDMT, MFIS, MSQOL-54, PHQ9, EQ-5D-5L, and frequent co-registered research-quality MRI to sensitively assess for new inflammatory disease activity (new or enlarging T2 lesions), under schedules described in detail below. Biological sampling includes blood samples for functional immune profiling and stool samples for microbiome studies. Biomarker-based assessments are to include but not be limited to NfL and B cell levels.
Screening Period:
After obtaining informed consent, all screening assessments, and procedures to establish eligibility will be performed. These may be completed during one or more study visits within the 30-day screening window. Biological sampling with associated MRIs will include 2 samples obtained prior to initiation of OCR treatment.
Open-label Treatment Period:
Participants that meet all eligibility criteria for enrollment will be initiated on OCR using the standard approved administration and will be followed for 24 months under the standard of care clinical efficacy and safety monitoring described below. Biological sampling occurs at 6, 12, 18, and 24 months as well as prior to the 12 and 24 months visits (14 days +/- 7 days of the visit). MRIs will occur at 6, 12, 18, and 24 months.Participants who discontinue study therapy during the open-label treatment period are asked to return for an early withdrawal visit and a safety follow-up phone call approximately 6 months after their last dose.
Blinded Treatment Period:
At Month 24, participants will be randomized (2:1) to either: (Arm 1) placebo infusions every 6 months; or (Arm 2) continue with OCR infusions every 6 months. The blinded treatment period will extend to Month 48 or until new disease activity is observed. All participants in the blinded treatment period will be closely monitored clinically and with frequent research MRIs using a standard protocol that assesses for the development of any new inflammatory disease activity observed following Month 24. The development of such new inflammatory disease activity will represent the primary study endpoint. It will be defined as one or more of the following: (1) one or more new clinical relapse(s) (see relapse definition in section 3.2) or (2) MRI evidence on frequent (every 3 months) serial scans of new disease activity. The central imaging analysis will identify incident new or enlarging MRI T2 lesions as compared to prevalent brain lesions documented in each participant from Month 24 and thereafter.
Frequent biological sampling will include blood samples collected every 3 months and stool samples collected every 6 months through the 48-month end of study.
Unblinded Follow-up period:
For participants who discontinue blinded study therapy before Month 48, including those meeting the primary endpoint by manifesting new disease activity following Month 24 as defined above, blinded treatment allocation will be revealed and discussed, as described in section 3.5.1. Participants may choose to receive OCR or other treatment and are encouraged to continue with study assessments per the schedule of events. For participants that meet the primary endpoint, OCR will be provided by the study for those who choose to receive OCR after unblinding and continue with study assessments per the schedule of events.
Functional immune response profiles of reconstituting B cells as well as non-B cells (T cells and myeloid cells) will be compared between participants who do, versus those do not, benefit from durable remission of relapsing biology, to identify cellular immune response profiles that may underlie the state of durable tolerance versus lack of durable tolerance.
Safety Follow-up:
Participants who are treated with OCR through Month 48 will have a phone visit 6 months after their last dose. If there are safety concerns, the participant can be brought in for an unscheduled visit.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Ocrelizumab Arm
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.
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.
Placebo Arm
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.
Placebo for Ocrelizumab
Placebo infusions every 6 months from Month 30 through Month 48.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
Placebo for Ocrelizumab
Placebo infusions every 6 months from Month 30 through Month 48.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
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, including IV methylprednisolone administered according to the country label, including:
* Psychosis not controlled by a treatment
* Hypersensitivity to any of the constituents or excipients of the preceding steroids
18. Current or prior treatment with the following MS DMTs: fingolimod and other S1P receptor modulators, cladribine, natalizumab, anti-CD20 molecules, alemtuzumab, and chemotherapeutic agents
19. Treatment with fumarates within 30 days prior to collection of Mo 0/Day 0 mechanistic samples, Mo 0/Day 0 MRI, and Mo 0/Day 0 infusion
20. (a) Current or prior treatment with any approved or experimental immunomodulatory therapies, unless reviewed and approved by the SAC (Section 3.6), or (b) Treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
21. Systemic corticosteroid therapy within 4 weeks prior to the collection of screening mechanistic samples and the screening MRI
22. Systemic corticosteroid therapy within 4 weeks prior to the Mo 0/Day 0 infusion
23. Screening laboratory test results as follows:
* Positive infection screening tests for:
i. Hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) ii. Hepatitis C (HCV) antibody if positive screen for HCV RNA Polymerase Chain Reaction (PCR) iii. Rapid plasma reagin (RPR)
* A reactive RPR test unless followed by a subsequent negative RPR OR
* A reactive RPR test unless successful completion of treatment has been documented as well as a consultation with and clearance by infectious disease department iv. HIV v. At or within twelve months of screening:
* Positive QuantiFERON®-TB Gold test or positive purified protein derivative tuberculin skin test (PPD) (\>5mm induration, regardless of Bacille Calmette-Guerin (BCG) vaccine administration) unless completion of treatment has been documented for active TB OR
* An indeterminate QuantiFERON®-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON®-TB Gold test as well as a consultation with and clearance by infectious disease department
* Levels of serum immunoglobulin G (IgG) \< 3.3g/L
* Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.0 x the upper limit of normal (ULN)
* Platelet count \< 100,000 plt/µL (\<100 x 10⁹/L)
* Hemoglobin \< 10 g/dL
* Absolute neutrophil count \< 1.5 x 10⁹/L
* Absolute lymphocyte count \< 1.2 x 10⁹/L
24. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
18 Years
55 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Autoimmunity Centers of Excellence (ACE)
UNKNOWN
Rho Federal Systems Division, Inc.
INDUSTRY
Genentech, Inc.
INDUSTRY
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Amit Bar-Or, M.D.
Role: STUDY_CHAIR
University of Pennsylvania, Perelman School of Medicine: Department of Neurology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Yale School of Medicine
New Haven, Connecticut, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 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
The University of Texas Health Science Center at Houston, McGovern Medical School
Houston, Texas, United States
Virginia Commonwealth University School of Medicine
Richmond, Virginia, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Amit Bar-Or
Role: CONTACT
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Related Links
Access external resources that provide additional context or updates about the study.
Autoimmunity Centers of Excellence
National Institute of Allergy and Infectious
Division of Allergy, Immunology, and Transplantation
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DAIT AMS05
Identifier Type: -
Identifier Source: org_study_id