Clinical trial NCT01485003: Observational Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus Antibody Negative Participants
Official title: A Multicenter, Observational, Open-Label, Single-Arm Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JCV Antibody Negative Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Relapsing-Remitting Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2011-12-05
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants will be recruited by participating neurologists from among their MS patients who opt to begin treatment with Tysabri.

Brief summary: The primary objective of the study is to determine which baseline and yearly response factors (clinical and para clinical) predict overall disease-free status at Month 12 and Month 24, and clinical disease-free status in subsequent Months 36 and 48. The secondary objectives are: To identify prognostic factors at Baseline that predict overall disease-free status at Month 12, and to assess if yearly overall disease-free response factors predict overall disease-free status at Month 24; To evaluate clinical disease-free status (relapse, Expanded Disability Status Scale \[EDSS\]) at each analysis time point of Months 12, 24, 36, and 48; To identify prognostic factors at Baseline that predict clinical disease-free status at Month 12, and to assess yearly clinical disease-free response factors that predict clinical disease-free status (relapse, EDSS) in subsequent years at Months 24, 36, and 48; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: annualized relapse rate (ARR), sustained EDSS progression and improvement (24-week sustained); To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: magnetic resonance image (MRI) measures: T2, T1, T1 with Gadolinium (Gd), brain atrophy; To evaluate the impact of Tysabri at Month 24 and Month 48 on the following: optical coherence tomography (OCT), Low and High Contrast Visual Acuity Assessment; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: cognitive impairment (Symbol Digit Modalities Test \[SDMT\]), capacity for work (Work Productivity and Activity Impairment Questionnaire \[WPAI\]), quality of life (QoL) (Multiple Sclerosis Impact Scale \[MSIS-29\])


Eligibility criteria: Key Inclusion Criteria:

* Documented diagnosis of Relapsing Multiple Sclerosis (McDonald 2010 Criteria ).
* \<3 year disease duration.
* Must have an Expanded Disability Status Scale (EDSS) score from 0 to 4.0, inclusive.
* Anti-JCV antibody negative test within 6 months of Screening Visit.
* Must satisfy the approved therapeutic indications for Tysabri.
* Must be treatment-naïve to disease-modifying therapy (DMT) or have been treated with DMT (including but not limited to Avonex, Betaseron, Rebif, Copaxone, Extavia, or Gilenya) for ≤36 months total prior to date of informed consent.
* Decision to treat with Tysabri must precede enrollment.

Key Exclusion Criteria:

* Any prior treatment with Tysabri.
* Anti-JCV antibody positive at any timepoint prior to the Screening Visit.
* Contraindications to treatment with Tysabri as described in the US Prescribing Information.
* History of progressive multifocal leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections.
* History of diagnosis of Primary Progressive Multiple Sclerosis (PPM) and/or Secondary Progressive Multiple Sclerosis (SPMS).
* Receiving immunomodulatory or immunosuppressive therapy.
* Prior history of immunosuppressive use (mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab).
* Immunocompromised at the time of enrollment.
* Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
* Women breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception.
* Inability to comply with study requirements.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of Participants who are overall disease activity-free at Months 12 and 24
timeFrame: Baseline and Months 12 and 24
measure: Proportion of participants who are clinical disease activity-free at Months 36 and 48
timeFrame: Baseline and Months 36 and 48
Secondary outcomes:
measure: Identification of baseline prognostic factors that predict overall disease-free status
timeFrame: Baseline and Month 12
measure: Identification of yearly overall disease-free response factors that predict overall disease-free status
timeFrame: Month 12 and Month 24
measure: Number of Participants with Clinical Disease-Free Status Measured by Relapses
timeFrame: Months 12, 24, 36, and 48
measure: Identification of baseline prognostic factors that predict clinical disease-free status
timeFrame: Month 12
measure: Identification of yearly clinical disease-free response factors that predict clinical disease-free status
timeFrame: Months 24, 36 and 48
measure: Annualized Relapse Rate
timeFrame: Months 12, 24, 36, and 48
measure: Percentage of participants with Sustained EDSS progression
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: Sustained EDSS improvement
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: Change form baseline in number of new or newly enlarging T2 hyperintense lesions as assessed by MRI
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: Change from baseline in number of new T1 hypointense lesions as assessed by MRI
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: Change form baseline in number of T1 lesions with Gd-enhancing lesions as assessed by MRI
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: MRI brain atrophy as assessed by MRI
timeFrame: Baseline and Months 12, 24, 36, and 48
measure: Change from baseline in retinal nerve fiber layer (RNFL) thickness as assessed by OCT
timeFrame: Baseline and Month 24 and Month 48
measure: Change from baseline in low contrast visual acuity
timeFrame: Baseline and Month 24 and Month 48
measure: Change from baseline in high contrast visual acuity
timeFrame: Baseline and Month 24 and Month 48
measure: Cognitive impairment as assessed by change from baseline in SDMT
timeFrame: Baseline and Months 12, 24, 36 and 48
measure: Capacity for work as assessed by change from baseline in WPAI questionnaire
timeFrame: Baseline and Months 12, 24, 36 and 48
measure: Quality of Life as measured by MSIS-29
timeFrame: Baseline and Months 12, 24, 36 and 48
measure: Number of Participants with Clinical Disease-Free Status Measured by EDSS
timeFrame: Months 12, 24, 36 and 48
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Research Site
state: Alabama
city: Sun City
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Fort Collins
country: United States
facility: Research Site
state: Colorado
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Lake Barrington
country: United States
facility: Research Site
state: Illinois
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Lexington
country: United States
facility: Research Site
state: Massachusetts
city: Wellesley Hills
country: United States
facility: Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Research Site
state: Massachusetts
city: East Lansing
country: United States
facility: Research Site
state: Michigan
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Freehold
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Patchogue
country: United States
facility: Research Site
state: New York
city: Plainview
country: United States
facility: Research Site
state: New York
city: Staten Island
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Gahanna
country: United States
facility: Research Site
state: Ohio
city: Uniontown
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Perumal J, Balabanov R, Su R, Chang R, Balcer LJ, Galetta SL, Avila RL, Rutledge D, Fox RJ. Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study. CNS Drugs. 2022 Sep;36(9):977-993. doi: 10.1007/s40263-022-00950-0. Epub 2022 Sep 5.
citation: Perumal J, Balabanov R, Su R, Chang R, Balcer L, Galetta S, Campagnolo DI, Avila R, Lee L, Rutledge D, Fox RJ. Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study. Adv Ther. 2021 Jul;38(7):3724-3742. doi: 10.1007/s12325-021-01722-w. Epub 2021 May 20.
citation: Perumal J, Fox RJ, Balabanov R, Balcer LJ, Galetta S, Makh S, Santra S, Hotermans C, Lee L. Outcomes of natalizumab treatment within 3 years of relapsing-remitting multiple sclerosis diagnosis: a prespecified 2-year interim analysis of STRIVE. BMC Neurol. 2019 Jun 8;19(1):116. doi: 10.1186/s12883-019-1337-z.