Clinical trial NCT03157830: Evaluating the Efficacy and Safety of Transitioning Patients From Natalizumab to Ocrelizumab
Official title: Evaluating the Efficacy and Safety of Transitioning Patients From Natalizumab to Ocrelizumab
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
MS
ocrelizumab
OCREVUS
Natalizumab
Tysabri
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2017-05-17
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female patients with relapsing forms of MS, ages 18 to 65, must have received a stable dose of NTZ for 12 or more consecutive months, and have been free of relapses, disability worsening or MRI progression 6 months prior to switching from NTZ to OCR therapy are eligible to participate.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Relapse Free Survival at Month 12
timeFrame: 12 Months
Secondary outcomes:
measure: Relapse Rate at Months 3, 6, and 9
timeFrame: 3, 6, and 9 months
measure: MRI Evidence of MS Disease Activity at Months 3, 6, and 12
timeFrame: 3, 6, and 12 Months
measure: New or Enlarging T2 Lesions at 3, 6, and 12 Months
timeFrame: 3, 6, and 12 months
measure: New Gd+ Lesions Detected at Months 3, 6, and 12
timeFrame: 3, 6, and 12 months
measure: Change in the EDSS Score From Baseline to Month 12
timeFrame: 12 months
measure: Change in MSIS-29 From Baseline to Months 6 and 12
timeFrame: 6 and 12 months
measure: Proportion of Patients That Discontinued OCR
timeFrame: 12 months
Other outcomes:
Locations:
city: Livingston
country: United States
facility: RWJBarnabas Health
state: New Jersey
city: Portland
country: United States
facility: Providence MS Center
state: Oregon
city: Richland
country: United States
facility: Kadlec Neuroscience Center
state: Washington
city: Seattle
country: United States
facility: Multiple Sclerosis Center, Swedish Neuroscience Institute
state: Washington
city: Spokane
country: United States
facility: Providence Multiple Sclerosis Center
state: Washington
Study officials:
affiliation: Providence Brain & Spine Institute
name: Kyle Smoot, MD
role: PRINCIPAL_INVESTIGATOR
References: