Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Interventions
- Biological: Interferon beta-1aBiological: Alemtuzumab
- Registration Number
- NCT00530348
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief Summary
The purpose of this study was to establish the efficacy and safety of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous (SC) interferon beta-1a (Rebif®). The study had enrolled participants who had not previously received MS disease-modifying therapies. Participants had monthly laboratory tests and comprehensive testing every 3 months.
- Detailed Description
Every participant had received active treatment; there was no placebo. Participants who qualified were randomly assigned to treatment with either alemtuzumab or SC interferon beta-1a at a 2:1 ratio (that is, 2 given alemtuzumab for every 1 given interferon beta-1a). Alemtuzumab was administered in two annual courses, once at the beginning of the study and again 1 year later. Interferon beta-1a was self-injected 3 times per week for 2 years. All participants were required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests were performed at least monthly. Participation in this study ended 2 years after the start of treatment for each participant. Additionally, participants who received alemtuzumab might be followed in CAMMS03409 (NCT00930553) an extension study for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab on the extension study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 581
- Given written/signed informed consent
- Age 18 to 50 years old (inclusive) as of the date the informed consent form (ICF) was signed
- Diagnosis of MS per updated McDonald criteria, and cranial magnetic resonance imaging (MRI) scan demonstrating white matter lesions attributable to MS within 5 years of screening
- Onset of MS symptoms (as determined by a neurologist, either at screening or retrospectively) within 5 years of the date the ICF was signed
- Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at screening
- Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior to the date the ICF was signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider and the objective signs could be identified retrospectively
- Received prior therapy for MS other than corticosteroids, for example, alemtuzumab, interferons, intravenous immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone
- Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment
- Any progressive form of MS
- History of malignancy (except basal skin cell carcinoma)
- CD4 + , CD8 + count, B cell, or absolute neutrophil count less than (<) lower limit of normal (LLN) at screening
- Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen deficiency, or clotting factor deficiency)
- Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
- Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that is, above the LLN)
- Active infection or at high risk for infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interferon Beta-1a Interferon beta-1a - Alemtuzumab Alemtuzumab -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Accumulation of Disability (SAD) Up to 2 years 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: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least next 2 scheduled assessments, that is, 6 consecutive months. Onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
Annualized Relapse Rate Up to 2 years Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Were Relapse Free at Year 2 Year 2 Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2 Baseline, Year 2 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). Change was calculated by subtracting Baseline value from value at Year 2.
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2 Baseline, Year 2 MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in MSFC score at Year 2.
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2 Baseline, Year 2 Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)\*100/ (lesion volume at Baseline).
Trial Locations
- Locations (101)
Chernihiv Regional Hospital
🇺🇦Chernihiv, Ukraine
Northwest NeuroSpecialists, PLLC
🇺🇸Tucson, Arizona, United States
North Central Neurology Associates, P.C.
🇺🇸Cullman, Alabama, United States
Neurological Associates
🇺🇸Pompano Beach, Florida, United States
Associates in Neurology, PSC
🇺🇸Lexington, Kentucky, United States
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
University of Nevada School of Medicine
🇺🇸Las Vegas, Nevada, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Empire Neurology
🇺🇸Latham, New York, United States
Advanced Neurosciences Institute
🇺🇸Franklin, Tennessee, United States
Lehigh Valley Hospital Neurosciences and Pain Research
🇺🇸Allentown, Pennsylvania, United States
Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)
🇺🇸Charlotte, North Carolina, United States
Integra Clinical Research
🇺🇸San Antonio, Texas, United States
Neurology Center of San Antonio
🇺🇸San Antonio, Texas, United States
Royal Melbourne Hospital, Department of Neurology, Ward 4 East
🇦🇺Parkville, Victoria, Australia
Clinique Neuro rive-sud, Recherche Sepmus, Inc.
🇨🇦Greenfield park, Quebec, Canada
Krajska zdravotni a.s., Hospital Teplice
🇨🇿Teplice, Czech Republic
Nikolaevskaya Hospital
🇷🇺St. Petersburg, Russian Federation
Hospoital of the Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Department
🇺🇦Kyiv, Ukraine
Danylo Halytsky Lviv National Medical University
🇺🇦Lviv, Ukraine
Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry
🇬🇧London, England, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz
🇵🇱Lodz, Poland
Clinical Centre of Vojvodina, Clinic for neurology
🇷🇸Novi Sad, Serbia
Military Medical Academy
🇷🇸Belgrade, Serbia
Clinical centre Kragujevac
🇷🇸Kragujevac, Serbia
Federal State Institution Siberian Rettitorial Medical Center under Federal Medical-Biological Agency of Russia
🇷🇺Novosibirsk, Russian Federation
City Clinical Hospital #2
🇷🇺Pyatigorsk, Russian Federation
Clinical Neurology Centre Sp. z o.o. (Ltd)
🇵🇱Cracow, Poland
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center
🇺🇸Phoenix, Arizona, United States
Fort Wayne Neurological Center
🇺🇸Fort Wayne, Indiana, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Advanced Neurosciences Research
🇺🇸Fort Collins, Colorado, United States
MidAmerican Neuroscience Institute
🇺🇸Lenexa, Kansas, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Louisville Research Foundation
🇺🇸Louisville, Kentucky, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Hope Neurology PC
🇺🇸Knoxville, Tennessee, United States
The Ohio State University Medical Center, Multiple Sclerosis Center
🇺🇸Columbus, Ohio, United States
Oak Clinic for Multiple Sclerosis
🇺🇸Uniontown, Ohio, United States
MS Center of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Central Texas Neurology
🇺🇸Round Rock, Texas, United States
Baylor College of Medicine, Maxine Mesinger MS Clinic
🇺🇸Houston, Texas, United States
DIABAID
🇦🇷Buenos Aires, Argentina
The Wesley Research Institute
🇦🇺Auchenflower, Queensland, Australia
Griffith University School of Medicine
🇦🇺Southport, Queensland, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
St Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Hospital da Restauracao, Av Governador Agamenon Magalhaes
🇧🇷Recife, Pernambuco, Brazil
Hospital Sao Lucas PUC-RS
🇧🇷Porto Alegre, RS, Brazil
Hospital de Clínicas USP
🇧🇷Sao Paulo, SP, Brazil
University of Calgary and Foothills Medical Cenre
🇨🇦Calgary, Alberta, Canada
UBC Hospital
🇨🇦Vancouver, British Columbia, Canada
The Ottawa Hospital, General Campus
🇨🇦Ottawa, Ontario, Canada
Clinique Nuero-outaouais
🇨🇦Gatineau, Quebec, Canada
Clinical Hospital Centre Rijeka
🇭🇷Rijeka, Croatia
General Hospital Varazdin
🇭🇷Varazdin, Croatia
Oberhavelkliniken Hennigsdorf
🇩🇪Hennigsdorf, Germany
Department of Neurology, 1st Faculty of Medicine and General Teaching Hospital
🇨🇿Praha 2, Czech Republic
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Judisches Krankenhaus Berlin
🇩🇪Berlin, Germany
Clinical Hospital Centre "Sestre Milosrdnice"
🇭🇷Zagreb, Croatia
General Hospital "Sveti Duh"
🇭🇷Zagreb, Croatia
Hopital Purpan
🇫🇷Toulouse, France
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Institute of Human Brain RAS
🇷🇺St. Petersburg, Russian Federation
Universitätsklinik Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Asklepios Klinikum Brandenburg
🇩🇪Teupitz, Germany
Klinikum der Goethe Universität Frankfurt
🇩🇪Frankfurt, Germany
Moscow City Hospital #11
🇷🇺Moscow, Russian Federation
Hospital Medica Sur CIF-BIOTEC
🇲🇽Mexico City, Mexico
Hospital Angeles del Pedregal, Camino de Santa Teresa
🇲🇽Mexico City, Mexico
Independent Public Teaching Hospital No. 4 in Lublin
🇵🇱Lublin, Poland
Heliodor Swiecicki Teaching Hospital of the Poznan University of Medical Sciences
🇵🇱Poznan, Poland
Moscow State Medical Institution City Clinical Hospital #11
🇷🇺Moscow, Russian Federation
Scientific Neurology Center RAMS
🇷🇺Moscow, Russian Federation
Municipal City Hospital #33
🇷🇺Nizhniy Novgorod, Russian Federation
Research Medical Complex "Your Health" Ltd
🇷🇺Kazan, Russian Federation
Sahlgrenska University Hospital
🇸🇪Goteborg, Sweden
Samara Regional Clinical Hospital n.a. Kalinin
🇷🇺Samara, Russian Federation
Clinical Center Nis, Clinic for neurology
🇷🇸Nis, Serbia
State Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
🇷🇺Ufa, Russian Federation
St. Petersburg Pavlov State Medical University
🇷🇺St. Petersburg, Russian Federation
Clinical Centre Serbia, Institute for Neurology
🇷🇸Belgrade, Serbia
Kyiv Municipal Clinical Hospital #4
🇺🇦Kyiv, Ukraine
Department Of Neurosciences, Addenbrookes Hospital
🇬🇧Cambridge, England, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine, Department of Neuroinfection and Multiple Sclerosis
🇺🇦Kharkiv, Ukraine
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Biomedical Research Alliance of NY, LLC
🇺🇸Franklin, Tennessee, United States
Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
🇺🇸Patchogue, New York, United States
Westmead Hospital
🇦🇺Westmead, Australia
Consultants in Neurology, Ltd.
🇺🇸Northbrook, Illinois, United States
Idaho Falls Multiple Sclerosis Center, PLLC
🇺🇸Idaho Falls, Idaho, United States
University of New Mexico, Health Sciences Center, MS Specialty Clinic
🇺🇸Albuquerque, New Mexico, United States
Concord Repatriation General Hospital
🇦🇺Concord, Australia
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States