RECRUITING

Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-01-12

Study Completion:2028-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05285891

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 55 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) for up to 2 years post-event 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 ≤ 2 years 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	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 Magnetic resonance imaging (MRI) 4. Known presence or history of other neurological disorders, including but not limited to the following: 1. Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage 2. Central Nervous System (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 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 NY 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 Intravenous (IV) antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit 12. Active or chronic infection with Human Immunodeficiency Virus (HIV), syphilis or TB (see laboratory tests below) 13. Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection 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 baseline 17. Contraindications to or severe intolerance of oral or IV corticosteroids, including Intravenous (IV) methylprednisolone administered according to the country label, including: 1. Psychosis not controlled by a treatment 2. 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 baseline 20. Current or prior treatment with any experimental therapies (e.g., bone marrow transplant), investigational agent, or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency) 21. Systemic corticosteroid therapy within 4 weeks prior to screening 22. Laboratory test results as follows: * Positive QuantiFERON(R)-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 * An indeterminate QuantiFERON(R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department 23. 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

Inclusion Criteria

Exclusion Criteria

1. Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) for up to 2 years post-event 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 ≤ 2 years
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

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 Magnetic resonance imaging (MRI)
4. Known presence or history of other neurological disorders, including but not limited to the following:
1. Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
2. Central Nervous System (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
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 NY 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 Intravenous (IV) antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
12. Active or chronic infection with Human Immunodeficiency Virus (HIV), syphilis or TB (see laboratory tests below)
13. Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection
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 baseline
17. Contraindications to or severe intolerance of oral or IV corticosteroids, including Intravenous (IV) methylprednisolone administered according to the country label, including:
1. Psychosis not controlled by a treatment
2. 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 baseline
20. Current or prior treatment with any experimental therapies (e.g., bone marrow transplant), investigational agent, or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
21. Systemic corticosteroid therapy within 4 weeks prior to screening
22. Laboratory test results as follows:
* Positive QuantiFERON(R)-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
* An indeterminate QuantiFERON(R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department
23. 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

Contacts and Locations

Study Contact

Amit Bar-Or

CONTACT

(215) 316-5151

Principal Investigator

Amit Bar-Or, M.D.

STUDY_CHAIR

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

Study Locations (Sites)

Yale School of Medicine

New Haven, Connecticut, 06510

United States

MedStar Georgetown University Hospital

Washington, District of Columbia, 20007

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10007

United States

University of Rochester Medical Center

Rochester, New York, 14627

United States

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104

United States

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19104

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

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

Houston, Texas, 77030

United States

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Amit Bar-Or, M.D., STUDY_CHAIR, University of Pennsylvania, Perelman School of Medicine: Department of Neurology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-12

Study Completion Date2028-08-01

Study Record Updates

Study Start Date2023-01-12

Study Completion Date2028-08-01

Terms related to this study

Keywords Provided by Researchers

Ocrelizumab
Multiple sclerosis
Relapse

Additional Relevant MeSH Terms

Multiple Sclerosis