We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ocrevus, RIS
Previous Study | Return to List | Next Study

Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease. (CELLO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04877457
Recruitment Status : Recruiting
First Posted : May 7, 2021
Last Update Posted : October 26, 2022
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Erin Longbrake, Yale University

Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 4 study in which eligible patients with RADIOLOGICALLY ISOLATED SYNDROME (RIS) (as defined by meeting 2017 McDonald criteria for DIS) will be randomized 1:1 to receive ocrelizumab treatment or placebo (standard of care).

Condition or disease Intervention/treatment Phase
Radiologically Isolated Syndrome Multiple Sclerosis Drug: Ocrelizumab Other: Placebo Phase 4

Detailed Description:
This study is designed to investigate the treatment effect of ocrelizumab compared with placebo on clinical and radiological outcomes in patients with RIS (i.e., asymptomatic CNS lesions fulfilling the 2017 McDonald criteria for DIS), as well as neuroimaging, serologic, immunologic and other exploratory biomarkers of MS disease biology in order to improve the understanding of B cell biology in early disease pathophysiology, characterize the emergence of CNS autoimmunity, and the mechanism of action of ocrelizumab in this population.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Randomization and blinding will be employed to minimize bias in treatment assignment and to provide the basis for valid statistical inference.
Primary Purpose: Prevention
Official Title: A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Ocrelizumab in Patients With Radiologically Isolated Syndrome
Actual Study Start Date : February 15, 2022
Estimated Primary Completion Date : July 2028
Estimated Study Completion Date : July 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arm Intervention/treatment
Experimental: Ocrelizumab
Three courses of ocrelizumab will be administered over the course of the study.
Drug: Ocrelizumab
The first course of ocrelizumab will be administered as two 300 mg infusions at Week 0 (Day 1) and Week 2 (Day 15), with the subsequent second- and third-courses given as a single 600 mg infusion at Weeks 24 and 48.

Placebo Comparator: Placebo
Three courses of placebo will be administered over the course of the study.
Other: Placebo
Placebo will be administered at Week 0 (Day 1) and Week 2 (Day 15), with the subsequent second- and third-courses given at Weeks 24 and 48.




Primary Outcome Measures :
  1. Time to development of first new radiologic or clinical evidence of MS [ Time Frame: Up 4 years ]
    The primary efficacy endpoint for this study is to evaluate the efficacy of ocrelizumab compared with placebo on delaying the time to development of new radiological or clinical evidence of MS, defined as the time from baseline to first new T1 gadolinium-enhancing lesions and/or new or enlarging T2 lesions consistent with MS OR first clinical evidence of MS, i.e., neurological event resulting from CNS demyelination as evidenced by acute or progressive clinical syndrome consistent with MS.


Secondary Outcome Measures :
  1. Cumulative number of new or enlarging T2 lesions [ Time Frame: Up to 4 years ]
    MRI scans will be used to determine the number of new or enlarging T2 lesions

  2. Change in T2-lesion volume [ Time Frame: Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks ]
    MRI scans will be used to the change in T2 lesions

  3. Cumulative number of new T1 gadolinium-enhancing lesions [ Time Frame: Up to 4 years ]
    MRI scans will be used to determine the cumulative number of new T1 gadolinium-enhancing lesions

  4. Change in total brain volume [ Time Frame: Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks ]
    MRI scan will be used to determine the change in total brain volume

  5. Change in total spinal cord volume [ Time Frame: Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks ]
    MRI scan will be used to determine the change in total brain volume

  6. Change in serum NfL (sNfL) [ Time Frame: Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 130 weeks, 156 weeks, 182 weeks, 208 weeks ]
    Change in serum Nfl will be used measured



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for screening:

  • Age 18-40
  • No prior exposure to long term immunomodulatory medications
  • One of the following:

    • First degree family member of an individual with clinically definite MS who was identified to have CNS lesions meeting McDonald 2017 criteria for DIS during a pre-screening MRI.
    • Established RIS diagnosis (i.e. CNS lesions consistent with MS, meeting McDonald 2017 criteria for DIS), either diagnosed within the last 5 years or known to have had accumulation of CNS lesions within the last 5 years.

Inclusion criteria for randomization:

  1. Signed Informed Consent Form
  2. Aged 18-40 years at time of signing Informed Consent Form
  3. Ability to provide written informed consent and be compliant with the study protocol
  4. CNS lesions consistent with MS, meeting McDonald 2017 criteria for DIS
  5. RIS diagnosis established within last 5 years OR with known accumulation of CNS lesions within last 5 years
  6. No alternative diagnosis established during serologic workup for MS mimics
  7. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of <1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 24 weeks after the last dose of study treatment.

    • 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 of other than menopause), and has not undergone surgical sterilization (removal of the ovaries and/or uterus)
    • Examples of contraceptive methods with a failure rate of <1% per year 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 patient. Periodic abstinence and withdrawal are not acceptable methods of contraception.
    • Examples of barrier methods supplemented with the use of spermicide include male or female condom, cap, diaphragm, or sponge.

Exclusion criteria:

  1. Intolerance to gadolinium-based contrast agent
  2. Contraindications to MRI
  3. >5 years of radiologic stability since first known abnormal MRI for patients previously diagnosed with RIS
  4. History of remitting clinical symptoms consistent with MS lasting >24 hours prior to CNS imaging revealing anomalies suggestive of MS
  5. CNS MRI anomalies are better accounted for by another disease process
  6. Infection Related

    • Known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
    • History of recurrent aspiration pneumonia requiring antibiotic therapy
    • History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy)
    • Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
  7. Cancer Related

    • History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix or the uterus that have been excised and resolved with documented clean margins on pathology)
  8. Pregnant or lactating, or intending to become pregnant during the treatment phase and 6 months after the last infusion of study drug

    • Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study drug.
  9. Other Medical Conditions

    • History of or currently active primary or secondary immunodeficiency
    • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
    • History of alcohol or other drug abuse within 24 weeks prior to enrollment
    • History or known presence of systemic autoimmune disorders associated with systemic symptoms (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren's syndrome, Behçet's disease)
    • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
    • Significant, uncontrolled disease, as defined by AMA guidelines or similar, such as cardiovascular (including congestive heart failure - NYHA grade 3 or 4, cardiac arrhythmia), uncontrolled hypertension, pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), gastrointestinal, or any other significant disease
    • Known presence or history of other neurologic disorders, including but not limited to, the following:

      • Progressive multifocal leukoencephalopathy, CNS or spinal cord tumor, potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)
      • History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS])
      • Neuromyelitis optica spectrum disorders (NMOSD)
      • Ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord
      • Severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression)
      • Psychosis not yet controlled by a treatment
  10. Drug Related

    • Systemic, high dose corticosteroid therapy within 4 weeks prior to screening
    • Contraindications for, or intolerance to, oral or IV corticosteroids, including IV methylprednisolone, according to the country label, including hypersensitivity to any of the treatment drug constituents
  11. Prior exposure to immunomodulatory medications and/or DMT

    • Prior treatment with any disease modifying therapy for MS including but not limited to: interferon (IFN-β-1a (Avonex, Rebif), IFN-β-1b (Betaseron/Betaferon), glatiramer acetate, dimethyl fumarate (DMF; Tecfidera), diroximel fumarate (Vumerity) fingolimod (Gilenya) or siponimod (Mayzent), ozanimod (Zeposia) natalizumab (Tysabri), alemtuzimab (Lemtrada), cladribine (Mavenclad), rituximab (Rituxan), and other anti-CD20 agents
    • Previous treatment with cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
    • Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
    • Vaccinations: Receipt of a live or live-attenuated vaccine or an inactivated/non-live vaccine within 6 weeks prior to enrollment
  12. Laboratory: Certain laboratory abnormalities or findings at screening, including the following:

    • Positive serum β-hCG
    • Positive for hepatitis B (hepatitis B surface antigen [HBsAg] positive or hepatitis B core antibody [total HBcAb] confirmed by positive viral DNA polymerase chain reaction [PCR])
    • AST or ALT >3.0x upper limit of normal
    • Total white blood cell count, including differential counts, below lower limit of normal
    • Absolute lymphocyte count below lower level of normal
    • Absolute neutrophil count below lower limit of normal
    • Platelet count below lower limit of normal

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04877457


Contacts
Layout table for location contacts
Contact: Lesa Moemeka (203) 737-5437 lesa.moemeka@yale.edu

Locations
Layout table for location information
United States, California
USC, Keck School of Medicine Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Sylvia William    323-442-6833    sylviawi@usc.edu   
Principal Investigator: Lilyana Amezcua, MD, MS         
United States, Connecticut
Yale University Recruiting
North Haven, Connecticut, United States, 06473
Contact: Yale University    203-287-6100    msresearch@yale.edu   
Principal Investigator: Erin Longbrake, MD, PhD         
United States, District of Columbia
Georgetown University Not yet recruiting
Washington, District of Columbia, United States, 20007
Contact: Zsofia Parragh       zp53@georgetown.edu   
Principal Investigator: Benjamin Osborne, MD         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Meredith Hasenoehrl         
Principal Investigator: Farrah Mateen, MD, PhD         
The Elliot Lewis Center for Multiple Sclerosis Care Recruiting
Wellesley, Massachusetts, United States, 02481
Contact: Elizabeth Douglas       elizabethdouglas@elliotlewisms.org   
Principal Investigator: Joshua Katz, MD         
United States, Missouri
Washington University- St. Louis Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Susan sommer       foxs@wustl.edu   
Principal Investigator: Robert Naismith, MD         
United States, Nevada
Cleveland Clinic- Lou Ruvo Center for Brain Health Not yet recruiting
Las Vegas, Nevada, United States, 89106
Contact: Meagan Jensen       healthybrains@ccf.org   
Principal Investigator: Le Hua, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Contact: Faye Bourie    212-241-9002    faye.bourie@mssm.edu   
Principal Investigator: Erin Beck, MD, PhD         
Northwell Not yet recruiting
New York, New York, United States, 10075
Contact: Olivia Colon       ocolon2@northwell.edu   
Principal Investigator: Asaff Harel, MD         
United States, Ohio
Cleveland Clinic Melen Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Megan Elder       elderm3@ccf.org   
Principal Investigator: Daniel Ontaneda, MD, PhD         
United States, Oklahoma
Oklahoma Medical Research Foundation Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Micki Drake       micki-drake@omrf.org   
Principal Investigator: Gabriel Pardo, MD         
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Margaux Giardano       msresearch@pennmedicine.upenn.edu   
Contact: Carly Cherwony       MSresearch@pennmedicine.upenn.edu   
Principal Investigator: Rachel Brandstadter, MD         
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84108
Contact: Trieste Francis       trieste.francis@hsc.utah.edu   
Principal Investigator: Mateo Paz Soldan, MD         
Sponsors and Collaborators
Yale University
Genentech, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Erin Longbrake, Assistant Professor of Neurology, Yale University
ClinicalTrials.gov Identifier: NCT04877457    
Other Study ID Numbers: 2000029952
ML42790 ( Other Identifier: Genentech, Inc. )
First Posted: May 7, 2021    Key Record Dates
Last Update Posted: October 26, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Ocrelizumab
Multiple Sclerosis
Syndrome
Sclerosis
Disease
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs