An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Interventions
- Biological: alemtuzumab
- Registration Number
- NCT00930553
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief Summary
This open-label, rater-blinded extension study enrolled participants who had relapsing-remitting multiple sclerosis (RRMS) and who participated in one of three prior Genzyme-sponsored studies of alemtuzumab (CAMMS223 \[NCT00050778\], CAMMS323 \[NCT00530348\] also known as CARE-MS I, or CAMMS324 \[NCT00548405\] also known as CARE-MS II). The purposes of this study were:
1. To examine the long term safety and efficacy of alemtuzumab treatment in participants who received alemtuzumab as their study treatment in one of the prior studies.
2. To examine the safety and efficacy of initial alemtuzumab treatment in this study for participants who received Rebif® (interferon beta-1a) as their study treatment in one of the prior studies.
3. To determine the safety and efficacy of additional "as needed" alemtuzumab treatment courses. This applied both to participants who received alemtuzumab for the first time in one of the prior studies or for the first time in this extension study.
- Detailed Description
Alemtuzumab treatment was on a fixed schedule of two treatment courses a year apart for participants who received Rebif® in one of the prior Genzyme-sponsored studies of alemtuzumab or on an as needed schedule (e.g. due to documented evidence of resumed Multiple Sclerosis \[MS\] activity) for participants who had already completed a fixed schedule of treatment with alemtuzumab in one of the prior Genzyme-sponsored studies. There was no comparison treatment in this study. All participants were required to return to their study site every 3 months for neurologic and other assessments. In addition, safety-related laboratory tests and surveys were performed at least monthly. Participation in the extension study was at least 48 months from enrollment. Study duration could be extended to allow participants to remain in the study until a follow-up study was available in their country or through month 60 (month 72 in USA), whichever occurred first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1314
- 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received disease modifying treatments (other than glatiramer acetate or interferon beta); or
- 2.Received Rebif® in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received alternative disease modifying treatments (other than glatiramer acetate or another interferon beta); or
- 3.Participated in CAMMS223.
- NOTE: Criteria 1 and 2 above meant that participants who enrolled in CAMMS323 or CAMMS324 but did not complete the 2-year study period or went on to receive non-study drug DMTs after randomization were not eligible for inclusion in the Extension Study. Participants who enrolled in CAMMS324 after participation in CAMMS223 must meet criteria 1 or 2 to be eligible for inclusion in the Extension Study.
- Any alemtuzumab participant from CAMMS223, CAMMS323, or CAMMS324 who had received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies), or was participating in any other investigational study, unless approved by Genzyme. In addition, these participants must be screened for disqualifying safety concerns before receiving alemtuzumab retreatment.
- Any Rebif® participants from CAMMS223, CAMMS323, or CAMMS324 who met any of the following criteria. In addition, these participants must be screened for disqualifying safety concerns before receiving alemtuzumab treatment. a) Did not wish to receive alemtuzumab; b) Ongoing participation in any other investigational study, unless approved by Genzyme; c) Had received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies); d) Known bleeding disorder or therapeutic anticoagulation; e) Diagnosis of idiopathic thrombocytopenia purpura or other autoimmune hematologic abnormality; f) History of malignancy, except basal cell skin carcinoma; g) Intolerance of pulsed corticosteroids, especially a history of steroid psychosis h) Significant Autoimmune disorder (other than MS); i) Major psychiatric disorder or epileptic seizures not adequately controlled by treatment; j) Active infection or high risk for infection k) Unwilling to use a reliable and acceptable contraceptive method during and for at least 6 months following each alemtuzumab treatment cycle (fertile participants only).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Previously treated with alemtuzumab alemtuzumab Alemtuzumab 12 mg per day administered through IV, once a day for 3 consecutive days (participants might receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period) Previously treated with interferon beta-1a (Rebif®) alemtuzumab Alemtuzumab 12 mg per day administered through IV, once a day for 5 consecutive days during the first cycle and 12 mg per day administered through IV, once a day for 3 consecutive days during the second cycle, 12 months later. Participants might qualify for as-needed retreatment (12 mg per day administered through IV, once a day for 3 consecutive days) after their second fixed annual cycle.
- Primary Outcome Measures
Name Time Method Annualized Relapse Rate (ARR) Year 3, 4, 5, 6 from the Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively) Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab Baseline (Year 0 of initial studies) up to Year 4 Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment Year 1 prior to retreatment, Year 1, 2, 3 after retreatment Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.
Number of Participants With Sustained Accumulation of Disability (SAD) Baseline (Year 0) up to Year 6 SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.
- Secondary Outcome Measures
Name Time Method Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment Baseline (Year 0 of initial studies) up to Year 4 Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment Retreatment baseline, Year 1, 2 and 3 after retreatment baseline EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6 Baseline (Year 0) up to Year 6 SRD was defined as a ≥1 point decrease in EDSS score lasting \>= 6 months. SRD is only applicable to participants with a baseline EDSS score of \>= 2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.
Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 \[NCT00530348\] or CAMMS324 \[NCT00548405\]) value from EDSS scores at specified time points.
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.
Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity Year 3, 4, 5 and 6 Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment Retreatment Baseline, Year 1, 2 and 3 after retreatment Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.
Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison Baseline (Year 0 of initial studies) up to Year 4 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.
Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity Year 3, 4, 5 and 6 Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.
Percentage of Relapse Free Participants Year 3, 4, 5 and 6 Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6 Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension group", "alemtuzumab Treatment CAMMS324 Extension" group, respectively),Year 3, 4, 5 and 6 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study Extension study (CAMMS03409) baseline up to Extension Year 2 SRD was defined as a \>=1 point decrease in EDSS score lasting \>=6 months. SRD is only applicable to participants with a baseline EDSS score of ≥2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Trial Locations
- Locations (176)
University of Southern California Keck School of Medicine/University of Southern California LAC & USC Medical Center
🇺🇸Los Angeles, California, United States
Jeroen Bosch Ziekenhuis
🇳🇱Den Bosch, Netherlands
University of Maryland, Maryland Center for MS
🇺🇸Baltimore, Maryland, United States
Kiev Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System
🇺🇦Kiev, Ukraine
Rigshospitalet Department of Neurology
🇩🇰Copenhagen, Denmark
Aarhus Sygehus
🇩🇰Århus C, Denmark
East Bay Physicians Medical Group/ Sutter East Bay Medical Foundation
🇺🇸Berkeley, California, United States
Northwest NeuroSpecialists, PLLC
🇺🇸Tucson, Arizona, United States
Neurology Center North Orange County
🇺🇸La Habra, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Florida Neuroscience Institute
🇺🇸Jacksonville, Florida, United States
Emory University Department of Neurology
🇺🇸Atlanta, Georgia, United States
Neurology Associates, P.A.
🇺🇸Maitland, Florida, United States
Neurological Associates
🇺🇸Pompano Beach, Florida, United States
Fort Wayne Neurological Center
🇺🇸Fort Wayne, Indiana, United States
Iowa Health Physicians
🇺🇸Des Moines, Iowa, United States
Associates in Neurology, P.S.C.
🇺🇸Lexington, Kentucky, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
MidAmerica Neuroscience Institute
🇺🇸Lenexa, Kansas, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Kansas Medical Center, Department of Neurology
🇺🇸Kansas City, Kansas, United States
MS Center at Holy Name Hospital
🇺🇸Teaneck, New Jersey, United States
Winthrop University Hospital Multiple Sclerosis Treatment Center
🇺🇸Mineola, New York, United States
Advanced Neurosciences Institute
🇺🇸Franklin, Tennessee, United States
Ruan Neurology Clinic and Clinical Research Center, Mercy Medical Center
🇺🇸Des Moines, Iowa, United States
Renown Institute for Neurosciences
🇺🇸Reno, Nevada, United States
Northern Michigan Neurology
🇺🇸Traverse City, Michigan, United States
Spectrum Health Medical Group, Neurology/Michigan Medical P.C., West Michigan MS Clinic
🇺🇸Grand Rapids, Michigan, United States
Michigan Neurology Association
🇺🇸Clinton, Michigan, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of New Mexico, Dept. of Neurology
🇺🇸Albuquerque, New Mexico, United States
Empire Neurology P.C.
🇺🇸Latham, New York, United States
MS Care Center at NYUMC and HJD
🇺🇸New York, New York, United States
South Shore Neurologic Associates, P.C.
🇺🇸Patchogue, New York, United States
Lehigh Valley Hospital Neurosciences and Pain Research
🇺🇸Allentown, Pennsylvania, United States
Oak Clinic for Multiple Sclerosis
🇺🇸Uniontown, Ohio, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
Rhode Island Hospital MS Center - The Neurology Foundation, Inc
🇺🇸Providence, Rhode Island, United States
DIABAID
🇦🇷Buenos Aires, Argentina
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
Swedish Medical MS Center
🇺🇸Seattle, Washington, United States
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
The Wesley Research Institute
🇦🇺Auchenflower QLD, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Gold Coast Hospital
🇦🇺Southport, Queensland, Australia
AKH Wien-Universitätskliniken für Neurologie
🇦🇹Vienna, Austria
Cliniques Universitaires Saint-luc
🇧🇪Brussel, Belgium
The Queen Elizabeth Hospital
🇦🇺Woodville, SA, Australia
Hospital Mae de Deus
🇧🇷Porto Alegre, Brazil
CHU Ourthe Amblève
🇧🇪Esneux, Belgium
University Hospital Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
Recherche Sepmus, Inc.
🇨🇦Greenfield Park, Quebec, Canada
Irmandade da Santa Casa de Misericórdio de São Paulo, Neurology department
🇧🇷São Paulo, SP, Brazil
Hospital Teplice, Neurology Department, MS centrum
🇨🇿Teplice, Czechia
London Health Sciences Centre - University Hospital
🇨🇦London, ON, Canada
University of Calgary, Department of Neurology
🇨🇦Calgary, Alberta, Canada
Kingston General Hospital MS Clinic
🇨🇦Kingston, Ontario, Canada
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
The Ottawa Hospital - MS Research
🇨🇦Ottawa, Ontario, Canada
Clinical Hospital Osijek
🇭🇷Osijek, Croatia
Clinical Hospital Centre Rijeka
🇭🇷Rijeka, Croatia
University of British Columbia
🇨🇦Vancouver, BC, Canada
St. Anne's University Hospital Brno
🇨🇿Brno, Czechia
Medizinische Fakultät der Universität Rostock,Zentrum für Nervenheilkunde
🇩🇪Rostock, Germany
General Hospital, 128 21 Praha 2
🇨🇿Prague, Czechia
University Hospital Hradec Králové
🇨🇿Hradec Kralove, Czechia
Universitätsklinik Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Klinikum Ingolstadt
🇩🇪Ingolstadt, Germany
Hôpital Général
🇫🇷Dijon Cedex, France
Groupe Hospitalier Pitié-Salpêtrière, Fédération de Maladies du System Nerveux Central
🇫🇷Paris Cedex 13, France
CHU Pontchaillou
🇫🇷Rennes Cedex 9, France
Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn
🇩🇪Bonn, DE, Germany
Hôpital Civil
🇫🇷Strasbourg Cedex, France
CHU de Toulouse, Hôpital Purpan
🇫🇷Toulouse Cedex 9, France
Jüdisches Krankenhaus Berlin
🇩🇪Berlin-Mitte, Germany
Klinikum der JW Goethe Universität
🇩🇪Frankfurt am Main, Germany
Asklepios Klinik Barmbek
🇩🇪Hamburg, Germany
Oberhavel Klinicum GmbH - Krankenhaus Hennigsdorf
🇩🇪Hennigsdorf, Germany
Klinikum rechts der Isar
🇩🇪München, Germany
Universita Degli Studi di Roma "La Sapienza"
🇮🇹Roma, Italy
Università di Cagliari
🇮🇹Cagliari, Italy
Universitätsklinikum Ulm, Klinik für Neurologie im RKU
🇩🇪Ulm, Germany
Ospedale S. Luigi Gonzaga
🇮🇹Orbassano (TO), Italy
Hospital Universitario Vall d' Hebron
🇪🇸Barcelona, Spain
Hospital Clínico Universitario San Carlos
🇪🇸Madrid, Spain
Federal State Public Medical Institution: Siberian District Medical Center under the Federal Agency
🇷🇺Novosibirsk, Russian Federation
Municipal Treatment and Prevention Institution, City Hospital #33
🇷🇺Nizhny Novgorod, Russian Federation
Clinical Centre Nis, Clinic of Neurology
🇷🇸Nis, Serbia
Military Medical Academy, Institute of Neurology
🇷🇸Belgrade, Serbia
SU/Östra sjukhuset
🇸🇪Göteborg, Sweden
Norrlands Universitets sjukhus
🇸🇪Umeå, Sweden
Hospital Virgen Macarena
🇪🇸Seville, Spain
Hospital Carlos Haya, Neurology Service
🇪🇸Málaga, Spain
Frenchay Hospital
🇬🇧Bristol, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
HOPE Research Institute
🇺🇸Phoenix, Arizona, United States
St. Joseph's Hospital and Medical Center Barrow Neurology Clinics - Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Indiana University Multiple Sclerosis Center
🇺🇸Indianapolis, Indiana, United States
The MS Center at St. Elizabeth's
🇺🇸Boston, Massachusetts, United States
Wayne State University, The School of Medicine, Department of Neurology
🇺🇸Detroit, Michigan, United States
OMRF Multiple Sclerosis Center of Excellence
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine, Maxine Mesinger MS Clinic
🇺🇸Houston, Texas, United States
Integra Clinical Research
🇺🇸San Antonio, Texas, United States
Neurology Center of San Antonio
🇺🇸San Antonio, Texas, United States
Hospital da Restauração, Neurology department
🇧🇷Recife, PE, Brazil
University Hospital of Wales, Dept of Neurology
🇬🇧Cardiff, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Municipal Public Medical Institution: City Hospital #2 of Pyatigorsk, Neurology Department
🇷🇺Pyatigorsk, Russian Federation
The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai
🇺🇸New York, New York, United States
Rochester Multiple Sclerosis Center
🇺🇸Rochester, New York, United States
SUNY Upstate Medical University, Department of Neurology
🇺🇸Syracuse, New York, United States
Neuro-Therapeutics, Inc.
🇺🇸Pasadena, California, United States
University of Colorado Health Science Center - Aurora
🇺🇸Aurora, Colorado, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
University of South Florida College of Medicine
🇺🇸Tampa, Florida, United States
University of Michigan Medical School
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Science Department of Neurology
🇺🇸Winston-Salem, North Carolina, United States
Hope Neurology
🇺🇸Knoxville, Tennessee, United States
North Central Neurology Associates, P.C.
🇺🇸Cullman, Alabama, United States
Mayo Clinic Arizona (Scottsdale)
🇺🇸Scottsdale, Arizona, United States
Advanced Neurology of Colorado
🇺🇸Fort Collins, Colorado, United States
The George Washington University Medical Faculty Associates
🇺🇸Washington, D.C., District of Columbia, United States
Negroski, Stein, Sutherland and Hanes Neurology
🇺🇸Sarasota, Florida, United States
Consultants in Neurology, LTD
🇺🇸Northbrook, Illinois, United States
Shepherd Center Multiple Sclerosis Institute
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
MS Center of Greater Washington
🇺🇸Vienna, Virginia, United States
St. Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Hospital das Clínicas da Faculdade de Medicina da USP, Neurology department
🇧🇷São Paulo,SP, Brazil
General Hospital Varazdin, Department for Neurology
🇭🇷Varazdin, Croatia
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Sourasky Tel Aviv Medical Center
🇮🇱Tel Aviv, Israel
Hadassah Medical Center Ein Karem
🇮🇱Ein Karem, Jerusalem, Israel
Fachkrankenhaus Hubertusburg GmbH, Klinik für Neurologie und Neurologische Intensivmedizin
🇩🇪Wermsdorf, Germany
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Kliniczny Nr1 im. Norberta Barlickiego
🇵🇱Lodz, Poland
Medica Sur
🇲🇽Mexico City, DFE, Mexico
Ospedale S. Antonio Abate di Gallarate
🇮🇹Gallarate (Varese), Italy
Centrum Neurologii Klinicznej Sp. Zo.o.
🇵🇱Krakow, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Poland
Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Med. im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Orbis Medisch Concern
🇳🇱Sittard-Geleen, Netherlands
Neurology Research Center under the Russian Academy of Medical Sciences
🇷🇺Moscow, Russian Federation
Institute of Psychiatry and Neurology/Instytut Psychiatrii i Neurologii
🇵🇱Warsaw, Poland
Research Medical Complex "Your Health" Ltd
🇷🇺Kazan, Russian Federation
Moscow State Public Medical Institution Clinical Hospital #11, Neurology Department
🇷🇺Moscow, Russian Federation
Russian State Medical University, Department of Neurology and Neurosurgery
🇷🇺Moscow, Russian Federation
Institute of Human Brain RAS, Laboratory of Neuroimmunology
🇷🇺St. Petersburg, Russian Federation
St Petersburg State Pavlov Medical University, Dept of Neurology and Neurosurgery with a Hospital
🇷🇺St. Petersburg, Russian Federation
St. Petersburg State Public Medical Institution: Nikolayevskaya Hospital
🇷🇺St. Petersburg, Russian Federation
St. Petersburg General Hospital #2, Neurology Department #2
🇷🇺St. Petersburg, Russian Federation
Samara Regional Clinical Hospital n.a. Kalinin
🇷🇺Samara, Russian Federation
State Public Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
🇷🇺Ufa, Russian Federation
Clinical Centre Serbia, Institute of Neurology,Dr.Subotica 6,Belgrade
🇷🇸Belgrade, Serbia
Hospital of Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Dept.
🇺🇦Kiev-21, Ukraine
Clinical Hospital Centre "Sestre Milosrdnice"
🇭🇷Zagreb, Croatia
Clinical Centre Kragujevac, Clinic of Neurology
🇷🇸Kragujevac, Serbia
Clinical Centre Vojvodina
🇷🇸Novi Sad, Serbia
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Unidad de Investigación en Salud
🇲🇽Chihuahua, CHH, Mexico
Clinical Hospital Sveti Duh
🇭🇷Zagreb, Croatia
Institute of Neurology, Psychiatry and Narcology under the AMS of Ukraine, Dep of Neuroinfection& MS
🇺🇦Kharkov, Ukraine
Lviv National Medical University n.a. Danylo Galytsky, Department of Neurology
🇺🇦Lviv, Ukraine
Yale MS Research Center
🇺🇸New Haven, Connecticut, United States
Saint Luke's Brain & Stroke Institute
🇺🇸Kansas City, Missouri, United States
Kentucky Neuroscience Research
🇺🇸Louisville, Kentucky, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Clinique Neuro-Outaouais
🇨🇦Gatineau, Quebec, Canada