Impact of Ocrelizumab on Cerebrospinal Fluid Biomarkers at Multiple Sclerosis Onset (IMPACT MS)

University of California San Francisco (UCSF)

Status and phase: Active, not recruiting; Phase 4

Conditions: Relapsing Multiple Sclerosis; Clinically Isolated Syndrome

Treatments: Drug: Ocrelizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04466150

RO-IIS-2018-10828

Details and patient eligibility

About

Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment favorably alters CSF markers of chronic inflammation.

Full description

Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome (CIS) patients age 18-50 will be treated with ocrelizumab within 90 days of first clinical MS/CIS presentation and re-dosed as maintenance therapy every 6 months for 3 years to see if treatment favorably alters CSF markers of chronic inflammation

Investigators hope data that will provide a foundation for further studies that treating relapsing MS patients at clinical onset (using a B-cell depleting therapy) may improve longer-term outcomes.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients must meet the following criteria to be included in this study:

• Signed Consent Form

• High-risk clinically isolated syndrome or relapsing MS Diagnosis (based on 2017 International Panel Criteria)

• Age 18-50 inclusive

• Screening within 90 days of first clinical demyelinating event typical of MS with 1 or more inactive lesions typical of MS

• No prior MS disease modifying therapy

• No corticosteroids within 7 days of first ocrelizumab treatment

• EDSS < 4.0

• A negative urine or serum pregnancy test must be available for premenopausal women and for women <12 months after the onset of menopause, unless they have undergone surgical sterilization.

• 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 tube 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 will be excluded from the study based on the following criteria:

• Pregnancy, lactation, or intention to become pregnant during the study
• Progressive MS (primary or secondary)
• Disease other than MS to explain the first demyelinating event; including AQP4 IgG seropositivity
• Unwilling or unsafe to proceed with CSF exams based on coagulopathy or anatomy or other considerations in the judgment of the study investigator
• Unwilling or unsafe to proceed with MRI
• Active hepatitis B virus infection
• Untreated latent or active tuberculosis
• Active hepatitis C virus infection
• HIV infection
• Hypersensitivity to trial medications
• History of life-threatening infusion reaction to MAbs

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Ocrelizumab treated

Active Comparator group

Description:

Participants age 18-50 with a first clinical presentation of MS or high-risk CIS diagnosed within 90 days of screening will be treated with ocrelizumab (300 mg IV x 2 doses given 2 weeks apart) at disease origin and with maintenance ocrelizumab 600 mg every 6 months through 30 months with a final study visit at 3 years

Treatment:

Drug: Ocrelizumab

Observational study cohort

No Intervention group

Description:

Subjects enrolled into an observational study matched for the same disease duration and who are either untreated or treated with alternate MS disease modifying therapies will serve as a parallel reference group