Clinical trial NCT00530348: Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One
Official title: A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2007-09-17
Enrollment: 581
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With Sustained Accumulation of Disability (SAD)
timeFrame: Up to 2 years
measure: Annualized Relapse Rate
timeFrame: Up to 2 years
Secondary outcomes:
measure: Percentage of Participants Who Were Relapse Free at Year 2
timeFrame: Year 2
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2
timeFrame: Baseline, Year 2
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2
timeFrame: Baseline, Year 2
measure: Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2
timeFrame: Baseline, Year 2
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates, P.C.
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute, St. Joseph's Hospital & Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Northwest NeuroSpecialists, PLLC
state: Arizona
city: Fort Collins
country: United States
facility: Advanced Neurosciences Research
state: Colorado
city: Pompano Beach
country: United States
facility: Neurological Associates
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Idaho Falls
country: United States
facility: Idaho Falls Multiple Sclerosis Center, PLLC
state: Idaho
city: Northbrook
country: United States
facility: Consultants in Neurology, Ltd.
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lenexa
country: United States
facility: MidAmerican Neuroscience Institute
state: Kansas
city: Lexington
country: United States
facility: Associates in Neurology, PSC
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Research Foundation
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Las Vegas
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico, Health Sciences Center, MS Specialty Clinic
state: New Mexico
city: Latham
country: United States
facility: Empire Neurology
state: New York
city: Patchogue
country: United States
facility: Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center (CMC), Neurosciences & Spine Institute (NSSI)
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Medical Center, Multiple Sclerosis Center
state: Ohio
city: Uniontown
country: United States
facility: Oak Clinic for Multiple Sclerosis
state: Ohio
city: Oklahoma City
country: United States
facility: MS Center of Oklahoma
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital Neurosciences and Pain Research
state: Pennsylvania
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Franklin
country: United States
facility: Biomedical Research Alliance of NY, LLC
state: Tennessee
city: Knoxville
country: United States
facility: Hope Neurology PC
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine, Maxine Mesinger MS Clinic
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Neurology Center of San Antonio
state: Texas
city: Buenos Aires
country: Argentina
facility: DIABAID
city: Auchenflower
country: Australia
facility: The Wesley Research Institute
state: Queensland
city: Southport
country: Australia
facility: Griffith University School of Medicine
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital, Department of Neurology, Ward 4 East
state: Victoria
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Recife
country: Brazil
facility: Hospital da Restauracao, Av Governador Agamenon Magalhaes
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas PUC-RS
state: RS
city: Sao Paulo
country: Brazil
facility: Hospital de Clínicas USP
state: SP
city: Calgary
country: Canada
facility: University of Calgary and Foothills Medical Cenre
state: Alberta
city: Vancouver
country: Canada
facility: UBC Hospital
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Gatineau
country: Canada
facility: Clinique Nuero-outaouais
state: Quebec
city: Greenfield park
country: Canada
facility: Clinique Neuro rive-sud, Recherche Sepmus, Inc.
state: Quebec
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Varazdin
country: Croatia
facility: General Hospital Varazdin
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre "Sestre Milosrdnice"
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: General Hospital "Sveti Duh"
city: Praha 2
country: Czech Republic
facility: Department of Neurology, 1st Faculty of Medicine and General Teaching Hospital
city: Teplice
country: Czech Republic
facility: Krajska zdravotni a.s., Hospital Teplice
city: Toulouse
country: France
facility: Hopital Purpan
city: Berlin
country: Germany
facility: Judisches Krankenhaus Berlin
city: Dresden
country: Germany
facility: Universitätsklinik Carl Gustav Carus Dresden
city: Frankfurt
country: Germany
facility: Klinikum der Goethe Universität Frankfurt
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hennigsdorf
country: Germany
facility: Oberhavelkliniken Hennigsdorf
city: Teupitz
country: Germany
facility: Asklepios Klinikum Brandenburg
city: Mexico City
country: Mexico
facility: Hospital Angeles del Pedregal, Camino de Santa Teresa
city: Mexico City
country: Mexico
facility: Hospital Medica Sur CIF-BIOTEC
city: Cracow
country: Poland
facility: Clinical Neurology Centre Sp. z o.o. (Ltd)
city: Lodz
country: Poland
facility: Independent Public Healthcare Facility, Norbert Barlicki University Hospital No. 1 of the Medical University of Lodz
city: Lublin
country: Poland
facility: Independent Public Teaching Hospital No. 4 in Lublin
city: Poznan
country: Poland
facility: Heliodor Swiecicki Teaching Hospital of the Poznan University of Medical Sciences
city: Kazan
country: Russian Federation
facility: Research Medical Complex "Your Health" Ltd
city: Moscow
country: Russian Federation
facility: Moscow City Hospital #11
city: Moscow
country: Russian Federation
facility: Moscow State Medical Institution City Clinical Hospital #11
city: Moscow
country: Russian Federation
facility: Scientific Neurology Center RAMS
city: Nizhniy Novgorod
country: Russian Federation
facility: Municipal City Hospital #33
city: Novosibirsk
country: Russian Federation
facility: Federal State Institution Siberian Rettitorial Medical Center under Federal Medical-Biological Agency of Russia
city: Pyatigorsk
country: Russian Federation
facility: City Clinical Hospital #2
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital n.a. Kalinin
city: St. Petersburg
country: Russian Federation
facility: Institute of Human Brain RAS
city: St. Petersburg
country: Russian Federation
facility: Nikolaevskaya Hospital
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Pavlov State Medical University
city: Ufa
country: Russian Federation
facility: State Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
city: Belgrade
country: Serbia
facility: Clinical Centre Serbia, Institute for Neurology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: Clinical centre Kragujevac
city: Nis
country: Serbia
facility: Clinical Center Nis, Clinic for neurology
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina, Clinic for neurology
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Chernihiv
country: Ukraine
facility: Chernihiv Regional Hospital
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology under the Academy of Medical Sciences of Ukraine, Department of Neuroinfection and Multiple Sclerosis
city: Kyiv
country: Ukraine
facility: Hospoital of the Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Department
city: Kyiv
country: Ukraine
facility: Kyiv Municipal Clinical Hospital #4
city: Lviv
country: Ukraine
facility: Danylo Halytsky Lviv National Medical University
city: Cambridge
country: United Kingdom
facility: Department Of Neurosciences, Addenbrookes Hospital
state: England
city: London
country: United Kingdom
facility: Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry
state: England
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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