Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease. (CELLO)
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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 |
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Recruitment Status :
Recruiting
First Posted : May 7, 2021
Last Update Posted : January 31, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Radiologically Isolated Syndrome Multiple Sclerosis | Drug: Ocrelizumab Other: Placebo | Phase 4 |
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ocrelizumab
Three courses of ocrelizumab will be administered over the course of the study.
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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. |
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Placebo Comparator: Placebo
Three courses of placebo will be administered over the course of the study.
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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. |
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
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.
| Ages Eligible for Study: | 18 Years to 40 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Pre-Screening of First-Degree Family Members
Family members must meet the following inclusion criteria for pre-screening:
Signed informed consent form First-degree family member of an individual with clinically definite MS Age 18-55 years No prior exposure to DMT or long-term immunomodulatory medications Willingness to participate in full study protocol, if RIS is discovered
Screening
Patients must meet the following inclusion criteria for screening:
Signed informed consent form
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.
Age 18-55 years No prior exposure to DMT or long-term immunomodulatory medications Willingness to participate in full study protocol
Randomization
Patients must meet the following criteria for study entry and randomization:
Signed Informed Consent Form Aged 18-55 years at time of signing Informed Consent Form Ability to provide written informed consent and be compliant with the study protocol CNS lesions consistent with MS, meeting McDonald 2017 criteria for DIS RIS diagnosis established within last 5 years OR with known accumulation of CNS lesions within last 5 years No alternative diagnosis established during serologic workup for MS mimics 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
Patients who meet any of the following criteria will be excluded from pre-screening, screening and randomization:
Intolerance to gadolinium-based contrast agent Contraindications to MRI 5 years of radiologic stability since first known abnormal MRI, for patients previously diagnosed with RIS History of remitting clinical symptoms consistent with MS lasting 24 hours prior to CNS imaging revealing anomalies suggestive of MS CNS MRI anomalies are better accounted for by another disease process, for patients previously diagnosed with RIS 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 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) 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.
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 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 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
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 less than or equal to 3.0, 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
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
| Contact: Lesa Moemeka | (203) 737-5437 | lesa.moemeka@yale.edu |
| 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, Florida | |
| University of South Florida Morsani Center | Not yet recruiting |
| Tampa, Florida, United States, 33612 | |
| Contact: Amber McPherson 813-974-9423 Amjackson@usf.edu | |
| Principal Investigator: Natalie Moreo, 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 | 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 | 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 | |
| The Boster Center for Multiple Sclerosis | Not yet recruiting |
| Columbus, Ohio, United States, 43235 | |
| Contact: Erin Woodburn 614-826-1298 erin.woodburn@bosterms.com | |
| Principal Investigator: Aaron Boster, MD | |
| 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 | |
| United States, Wisconsin | |
| Medical College of Wisconsin | Not yet recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Contact: Pam Dailey 262-689-1846 pdailey@mcw.edu | |
| Principal Investigator: Ahmed Obeidat, MD, PhD | |
| Responsible Party: | Erin E 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: | January 31, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 Ocrelizumab Immunologic Factors Physiological Effects of Drugs |