Evaluating the Efficacy and Safety of Transitioning Patients From Natalizumab to Ocrelizumab
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Registration Number
- NCT03157830
- Lead Sponsor
- Providence Health & Services
- 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 12 or more continuous infusions of NTZ, 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- Able to understand the purpose and risk of the study and provide signed informed consent document.
- Must have received 12 or more consecutive monthly infusions of NTZ, 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.
- History of primary or secondary progressive multiple sclerosis.
- Any mental condition of such that patient is unable to understand the nature, scope, and possible consequences of the study.
- Patients with a known history of hepatitis B, hepatitis C, tuberculosis, PML, or who are HIV positive.
- Any persistent or severe infection.
- Any malignancy within 5 years, except for basal or squamous cell skin lesions, which have been surgically excised, with no evidence of metastasis.
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Relapse Free Survival at Month 12 12 Months The proportion of relapse-free patients at month 12 after switching from natalizumab to ocrelizumab.
- Secondary Outcome Measures
Name Time Method Relapse Rate at Months 3, 6, and 9 3, 6, and 9 months Proportion of relapse-free patients at months 3, 6, and 9
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
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.
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
Trial Locations
- Locations (5)
RWJBarnabas Health
🇺🇸Livingston, New Jersey, United States
Multiple Sclerosis Center, Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
Kadlec Neuroscience Center
🇺🇸Richland, Washington, United States
Providence MS Center
🇺🇸Portland, Oregon, United States
Providence Multiple Sclerosis Center
🇺🇸Spokane, Washington, United States