Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS, ocrelizumab, OCREVUS, Natalizumab, Tysabri
Brief summary
The primary objective of this study is to assess the efficacy of Ocrelizumab (OCR) in Relapsing Multiple Sclerosis patients who have been previously treated with natalizumab (NTZ) by evaluating relapse rate, progression on MRI and disability progression.
Detailed description
This is a multicenter, prospective, open-label, Phase IV clinical trial. Patients with relapsing forms of Multiple Sclerosis (MS), ages 18 to 65, who have received a stable dose of NTZ for 12 or more consecutive months, and have been free of relapses, disability worsening or Magnetic Resonance Imaging (MRI) progression 6 months prior to the transition screening visit will be eligible for the study. After informed consent to participate has been obtained, the patient will have physical exam (PE), non-blinded Expanded Disability Status Scale (EDSS), MRI, Multiple Sclerosis Impact Scale (MSIS-29) and labs done for the screening visit to determine eligibility. Brain MRI with and without contrast will be performed with the standard MS protocol. MRIs will be performed with 3mm slice thickness with no gaps between slices. Patients will receive their first dose of OCR 4 to 6 weeks after the last dose of NTZ. Other baseline measures, including physical exam, EDSS, MSIS-29, and labs will be performed within 4 weeks of screening. Physical exam, non-blinded EDSS, and labs will be performed at month 3, month 6, month 9, and month 12. MSIS-29 will be performed at months 6 and 12. In addition, MRIs will be performed at months 3, 6, and 12.
Interventions
None listed
Sponsors
Genentech, Inc.
Providence Health & Services
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female with relapsing form of MS, age 18 to 65, inclusive, at the time of informed consent. * In the opinion of the investigator, able to understand the purpose and risk of the study and provide signed informed consent document. * Must have received a stable dose of NTZ for 12 or more consecutive months, and have had no evidence of on-NTZ disease activity (clinically or on MRI) for the 6 months prior to the screening visit. * Naïve to OCR. * No evidence, in the opinion of the investigators of significant cognitive limitation or psychiatric disorder that would interfere with the conduct of the study. * EDSS of ≤ 6.0 at screening. * Female patients of childbearing potential must practice effective contraception and continue contraception during the study.
Exclusion criteria
* History of primary or secondary progressive multiple sclerosis. * Evidence of active hepatitis B infection at screening. * Any mental condition of such that patient is unable to understand the nature, scope, and possible consequences of the study. * Patients with untreated hepatitis C or tuberculosis. Patients who have history of progressive multifocal leukoencephalopathy (PML) or known to be HIV positive, per standard care. * Any persistent or severe infection. * Pregnancy or lactation. * Significant or uncontrolled somatic disease or severe depression in the last year. * Inability to complete an MRI. * Previous treatment with B-cell targeted therapies. * Current use of immunosuppressive medication. * Patients who have had evidence of disease activity within the 6 months prior to screening. This includes MS relapse, or new or enlarging T2 lesions or Gd+ enhancing lesions, or disability progression. * Patients with any significant comorbidity that in the opinion of the investigator, would interfere with participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Free Survival at Month 12 | 12 Months | The proportion of relapse-free patients at month 12 after switching from natalizumab to ocrelizumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI Evidence of MS Disease Activity at Months 3, 6, and 12 | 3, 6, and 12 Months | Proportion of patients free from MRI evidence of MS disease activity at months 3, 6, and 12 |
| New or Enlarging T2 Lesions at 3, 6, and 12 Months | 3, 6, and 12 months | Proportion of patients with New or Enlarging T2 lesions at 3, 6, and 12 months. For patients with New or Enlarging T2 lesions, number of New and Enlarging T2 lesions. |
| New Gd+ Lesions Detected at Months 3, 6, and 12 | 3, 6, and 12 months | Proportion of patients with New Gd+ lesions detected at months 3, 6, and 12. For patients with New Gd+ lesions, number of New Gd+ lesions |
| Relapse Rate at Months 3, 6, and 9 | 3, 6, and 9 months | Proportion of relapse-free patients at months 3, 6, and 9 |
| Change in MSIS-29 From Baseline to Months 6 and 12 | 6 and 12 months | Average change in MSIS-29: Multiple Sclerosis Impact Scale (MSIS) is a patient reported outcome (PRO) measure, consisting of two subscales- physical impact of MS (20 items) and psychological impact (9 items). It asks subject to rate the impact MS has their daily life in the past 2 weeks (1=low impact to 4=large impact). Scores from individual items are summed to a total score. Physical impact score ranges from 20-80 and psychological impact scores ranges from 9-36. Higher scores indicate greater impact of MS on QoL. |
| Proportion of Patients That Discontinued OCR | 12 months | Proportion of patients that stop treatment with OCR for any reason |
| Change in the EDSS Score From Baseline to Month 12 | 12 months | Average change in EDSS score. The Expanded Disability Status Scale (EDSS) is an assessment used by neurologist to assess changes in the level of disability over time in patients with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scores are also based on measures of impairment in the 8 functional systems. Higher scores indicate greater impact of MS on QoL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ocrelizumab, OCREVUS Patients eligible for this study will be receiving OCREVUS as part of their routine care for MS treatment, and undergo the standard monitoring tests and procedures for MS patients receiving treatment. In addition, they will complete the EDSS scale on 6 occasions over a 12-month period, and the MSIS-29 on three occasions during the 12 month period for research. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ocrelizumab, OCREVUS |
|---|---|
| Age, Continuous | 43 Years |
| Disease duration | 11 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 43 |
| other Total, other adverse events | 36 / 43 |
| serious Total, serious adverse events | 8 / 43 |
Outcome results
Primary
Relapse Free Survival at Month 12
The proportion of relapse-free patients at month 12 after switching from natalizumab to ocrelizumab.
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab, OCREVUS | Relapse Free Survival at Month 12 | 95.2 Percentage of Participant Survival Rate |
Secondary
Change in MSIS-29 From Baseline to Months 6 and 12
Average change in MSIS-29: Multiple Sclerosis Impact Scale (MSIS) is a patient reported outcome (PRO) measure, consisting of two subscales- physical impact of MS (20 items) and psychological impact (9 items). It asks subject to rate the impact MS has their daily life in the past 2 weeks (1=low impact to 4=large impact). Scores from individual items are summed to a total score. Physical impact score ranges from 20-80 and psychological impact scores ranges from 9-36. Higher scores indicate greater impact of MS on QoL.
Time frame: 6 and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | Change in MSIS-29 From Baseline to Months 6 and 12 | Physical - Baseline to Month 6 | -1.346 score on MSIS29 Scale |
| Ocrelizumab, OCREVUS | Change in MSIS-29 From Baseline to Months 6 and 12 | Psychological - Baseline to Month 6 | -1.283 score on MSIS29 Scale |
| Ocrelizumab, OCREVUS | Change in MSIS-29 From Baseline to Months 6 and 12 | Physical - Baseline to Month 12 | 1.524 score on MSIS29 Scale |
| Ocrelizumab, OCREVUS | Change in MSIS-29 From Baseline to Months 6 and 12 | Psychological - Baseline to Month 12 | -0.6953 score on MSIS29 Scale |
Secondary
Change in the EDSS Score From Baseline to Month 12
Average change in EDSS score. The Expanded Disability Status Scale (EDSS) is an assessment used by neurologist to assess changes in the level of disability over time in patients with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scores are also based on measures of impairment in the 8 functional systems. Higher scores indicate greater impact of MS on QoL.
Time frame: 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | Change in the EDSS Score From Baseline to Month 12 | Baseline | 3.50 Score on EDSS |
| Ocrelizumab, OCREVUS | Change in the EDSS Score From Baseline to Month 12 | Month 12 | 3.50 Score on EDSS |
Secondary
MRI Evidence of MS Disease Activity at Months 3, 6, and 12
Proportion of patients free from MRI evidence of MS disease activity at months 3, 6, and 12
Time frame: 3, 6, and 12 Months
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing prior to MRI scans at month 3. Additionally two patients showed evidence of MRI activity prior to MRI scans.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | MRI Evidence of MS Disease Activity at Months 3, 6, and 12 | Proportion of patients free from MRI evidence of MS disease activity at 3 months | 92.31 percentage of patients free from MRI evi |
| Ocrelizumab, OCREVUS | MRI Evidence of MS Disease Activity at Months 3, 6, and 12 | Proportion of patients free from MRI evidence of MS disease activity at 6 months | 92.31 percentage of patients free from MRI evi |
| Ocrelizumab, OCREVUS | MRI Evidence of MS Disease Activity at Months 3, 6, and 12 | Proportion of patients free from MRI evidence of MS disease activity at 12 months | 92.31 percentage of patients free from MRI evi |
Secondary
New Gd+ Lesions Detected at Months 3, 6, and 12
Proportion of patients with New Gd+ lesions detected at months 3, 6, and 12. For patients with New Gd+ lesions, number of New Gd+ lesions
Time frame: 3, 6, and 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | New Gd+ Lesions Detected at Months 3, 6, and 12 | Proportion of patients with new Gd+ lesions at 3 months | 5.13 percentage of participants with new Gd+ |
| Ocrelizumab, OCREVUS | New Gd+ Lesions Detected at Months 3, 6, and 12 | Proportion of patients with new Gd+ lesions at 6 months | 0 percentage of participants with new Gd+ |
| Ocrelizumab, OCREVUS | New Gd+ Lesions Detected at Months 3, 6, and 12 | Proportion of patients with new Gd+ lesions at 12 months | 0 percentage of participants with new Gd+ |
Secondary
New or Enlarging T2 Lesions at 3, 6, and 12 Months
Proportion of patients with New or Enlarging T2 lesions at 3, 6, and 12 months. For patients with New or Enlarging T2 lesions, number of New and Enlarging T2 lesions.
Time frame: 3, 6, and 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | New or Enlarging T2 Lesions at 3, 6, and 12 Months | Proportion of participants with new or enlarging T1 and/or T2 lesions at 3 months | 4.65 percentage of participants with new or e |
| Ocrelizumab, OCREVUS | New or Enlarging T2 Lesions at 3, 6, and 12 Months | Proportion of participants with new or enlarging T1 and/or T2 lesions at 6 months | 0 percentage of participants with new or e |
| Ocrelizumab, OCREVUS | New or Enlarging T2 Lesions at 3, 6, and 12 Months | Proportion of participants with new or enlarging T1 and/or T2 lesions at 12 months | 0 percentage of participants with new or e |
Secondary
Proportion of Patients That Discontinued OCR
Proportion of patients that stop treatment with OCR for any reason
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab, OCREVUS | Proportion of Patients That Discontinued OCR | 4.65 percentage of participants |
Secondary
Relapse Rate at Months 3, 6, and 9
Proportion of relapse-free patients at months 3, 6, and 9
Time frame: 3, 6, and 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab, OCREVUS | Relapse Rate at Months 3, 6, and 9 | Proportion of relapse-free patients at months 3 | 100 percentage of relapse-free patients |
| Ocrelizumab, OCREVUS | Relapse Rate at Months 3, 6, and 9 | Proportion of relapse-free patients at months 6 | 100 percentage of relapse-free patients |
| Ocrelizumab, OCREVUS | Relapse Rate at Months 3, 6, and 9 | Proportion of relapse-free patients at months 9 | 97.67 percentage of relapse-free patients |