An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
3 other identifiers
interventional
1,314
21 countries
163
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2009
Longer than P75 for phase_3
163 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2009
CompletedFirst Posted
Study publicly available on registry
June 30, 2009
CompletedStudy Start
First participant enrolled
August 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2016
CompletedResults Posted
Study results publicly available
May 15, 2017
CompletedMay 15, 2017
May 1, 2017
6.5 years
June 26, 2009
February 16, 2017
May 2, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Annualized Relapse Rate (ARR)
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.
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)
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab
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.
Baseline (Year 0 of initial studies) up to Year 4
Annualized Relapse Rate (ARR) Before and After Alemtuzumab 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.
Year 1 prior to retreatment, Year 1, 2, 3 after retreatment
Number of Participants With Sustained Accumulation of Disability (SAD)
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.
Baseline (Year 0) up to Year 6
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison
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.
Baseline (Year 0 of initial studies) up to Year 4
Secondary Outcomes (20)
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6
Baseline (Year 0) up to Year 6
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
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
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
Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment
Retreatment baseline, Year 1, 2 and 3 after retreatment baseline
- +15 more secondary outcomes
Study Arms (2)
Previously treated with alemtuzumab
EXPERIMENTALAlemtuzumab 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®)
EXPERIMENTALAlemtuzumab 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.
Interventions
Alemtuzumab 12 mg/day IV infusion on 5 consecutive days if the participants had no prior alemtuzumab exposure (ie, first treatment course). All subsequent treatment courses were for 3 days only.
Eligibility Criteria
You may qualify if:
- 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
- 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
- Participated in CAMMS223.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genzyme, a Sanofi Companylead
- Bayercollaborator
Study Sites (176)
North Central Neurology Associates, P.C.
Cullman, Alabama, United States
HOPE Research Institute
Phoenix, Arizona, United States
St. Joseph's Hospital and Medical Center Barrow Neurology Clinics - Barrow Neurological Institute
Phoenix, Arizona, United States
Mayo Clinic Arizona (Scottsdale)
Scottsdale, Arizona, United States
Northwest NeuroSpecialists, PLLC
Tucson, Arizona, United States
East Bay Physicians Medical Group/ Sutter East Bay Medical Foundation
Berkeley, California, United States
Neurology Center North Orange County
La Habra, California, United States
University of Southern California Keck School of Medicine/University of Southern California LAC & USC Medical Center
Los Angeles, California, United States
Neuro-Therapeutics, Inc.
Pasadena, California, United States
Stanford University Medical Center
Stanford, California, United States
University of Colorado Health Science Center - Aurora
Aurora, Colorado, United States
Advanced Neurology of Colorado
Fort Collins, Colorado, United States
Yale MS Research Center
New Haven, Connecticut, United States
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
University of Florida Neuroscience Institute
Jacksonville, Florida, United States
Neurology Associates, P.A.
Maitland, Florida, United States
Neurological Associates
Pompano Beach, Florida, United States
Negroski, Stein, Sutherland and Hanes Neurology
Sarasota, Florida, United States
Axiom Clinical Research of Florida
Tampa, Florida, United States
University of South Florida College of Medicine
Tampa, Florida, United States
Emory University Department of Neurology
Atlanta, Georgia, United States
Shepherd Center Multiple Sclerosis Institute
Atlanta, Georgia, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Consultants in Neurology, LTD
Northbrook, Illinois, United States
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States
Indiana University Multiple Sclerosis Center
Indianapolis, Indiana, United States
Iowa Health Physicians
Des Moines, Iowa, United States
Ruan Neurology Clinic and Clinical Research Center, Mercy Medical Center
Des Moines, Iowa, United States
University of Kansas Medical Center, Department of Neurology
Kansas City, Kansas, United States
MidAmerica Neuroscience Institute
Lenexa, Kansas, United States
Associates in Neurology, P.S.C.
Lexington, Kentucky, United States
Kentucky Neuroscience Research
Louisville, Kentucky, United States
University of Maryland, Maryland Center for MS
Baltimore, Maryland, United States
The MS Center at St. Elizabeth's
Boston, Massachusetts, United States
UMass Memorial Medical Center
Worcester, Massachusetts, United States
University of Michigan Medical School
Ann Arbor, Michigan, United States
Michigan Neurology Association
Clinton, Michigan, United States
Wayne State University, The School of Medicine, Department of Neurology
Detroit, Michigan, United States
Spectrum Health Medical Group, Neurology/Michigan Medical P.C., West Michigan MS Clinic
Grand Rapids, Michigan, United States
Northern Michigan Neurology
Traverse City, Michigan, United States
Saint Luke's Brain & Stroke Institute
Kansas City, Missouri, United States
Renown Institute for Neurosciences
Reno, Nevada, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
MS Center at Holy Name Hospital
Teaneck, New Jersey, United States
University of New Mexico, Dept. of Neurology
Albuquerque, New Mexico, United States
Empire Neurology P.C.
Latham, New York, United States
Winthrop University Hospital Multiple Sclerosis Treatment Center
Mineola, New York, United States
MS Care Center at NYUMC and HJD
New York, New York, United States
The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai
New York, New York, United States
South Shore Neurologic Associates, P.C.
Patchogue, 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
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest University Health Science Department of Neurology
Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
OMRF Multiple Sclerosis Center of Excellence
Oklahoma City, Oklahoma, United States
Lehigh Valley Hospital Neurosciences and Pain Research
Allentown, Pennsylvania, United States
Rhode Island Hospital MS Center - The Neurology Foundation, Inc
Providence, Rhode Island, United States
Neurology Clinic PC
Cordova, Tennessee, United States
Advanced Neurosciences Institute
Franklin, Tennessee, United States
Hope Neurology
Knoxville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine, Maxine Mesinger MS Clinic
Houston, Texas, United States
Central Texas Neurology Consultants
Round Rock, Texas, United States
Integra Clinical Research
San Antonio, Texas, United States
Neurology Center of San Antonio
San Antonio, Texas, United States
MS Center of Greater Washington
Vienna, Virginia, United States
Swedish Medical MS Center
Seattle, Washington, United States
DIABAID
Buenos Aires, Argentina
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Southern Neurology
Kogarah, New South Wales, Australia
Liverpool Hospital
Liverpool, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Gold Coast Hospital
Southport, Queensland, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
St. Vincent's Hospital
Fitzroy, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
The Wesley Research Institute
Auchenflower QLD, Australia
The Queen Elizabeth Hospital
Woodville, SA, Australia
AKH Wien-Universitätskliniken für Neurologie
Vienna, Austria
Cliniques Universitaires Saint-luc
Brussels, Belgium
CHU Ourthe Amblève
Esneux, Belgium
University Hospital Leuven, Campus Gasthuisberg
Leuven, Belgium
Hospital Mae de Deus
Porto Alegre, Brazil
Hospital da Restauração, Neurology department
Recife, PE, Brazil
Irmandade da Santa Casa de Misericórdio de São Paulo, Neurology department
São Paulo, SP, Brazil
Hospital das Clínicas da Faculdade de Medicina da USP, Neurology department
São Paulo,SP, Brazil
University of Calgary, Department of Neurology
Calgary, Alberta, Canada
Kingston General Hospital MS Clinic
Kingston, Ontario, Canada
Clinique Neuro-Outaouais
Gatineau, Quebec, Canada
Recherche Sepmus, Inc.
Greenfield Park, Quebec, Canada
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada
London Health Sciences Centre - University Hospital
London, on, Canada
The Ottawa Hospital - MS Research
Ottawa, Ontario, Canada
University of British Columbia
Vancouver, BC, Canada
Clinical Hospital Osijek
Osijek, Croatia
Clinical Hospital Centre Rijeka
Rijeka, Croatia
General Hospital Varazdin, Department for Neurology
Varaždin, Croatia
Clinical Hospital Centre "Sestre Milosrdnice"
Zagreb, Croatia
Clinical Hospital Centre Zagreb
Zagreb, Croatia
Clinical Hospital Sveti Duh
Zagreb, Croatia
St. Anne's University Hospital Brno
Brno, Czechia
University Hospital Hradec Králové
Hradec Králové, Czechia
General Hospital, 128 21 Praha 2
Prague, Czechia
Hospital Teplice, Neurology Department, MS centrum
Teplice, Czechia
Aarhus Sygehus
Århus C, Denmark
Rigshospitalet Department of Neurology
Copenhagen, Denmark
Hôpital Général
Dijon, France
Groupe Hospitalier Pitié-Salpêtrière, Fédération de Maladies du System Nerveux Central
Paris, France
CHU Pontchaillou
Rennes, France
Hôpital Civil
Strasbourg, France
CHU de Toulouse, Hôpital Purpan
Toulouse, France
Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn
Bonn, DE, Germany
Universitätsklinik Carl Gustav Carus Dresden
Dresden, Germany
Klinikum der JW Goethe Universität
Frankfurt am Main, Germany
Asklepios Klinik Barmbek
Hamburg, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Oberhavel Klinicum GmbH - Krankenhaus Hennigsdorf
Hennigsdorf, Germany
Klinikum Ingolstadt
Ingolstadt, Germany
Jüdisches Krankenhaus Berlin
Mitte, Germany
Klinikum rechts der Isar
München, Germany
Medizinische Fakultät der Universität Rostock,Zentrum für Nervenheilkunde
Rostock, Germany
Universitätsklinikum Ulm, Klinik für Neurologie im RKU
Ulm, Germany
Fachkrankenhaus Hubertusburg GmbH, Klinik für Neurologie und Neurologische Intensivmedizin
Wermsdorf, Germany
Hadassah Medical Center Ein Karem
Ein Karem, Jerusalem, Israel
Sheba Medical Center
Ramat Gan, Israel
Sourasky Tel Aviv Medical Center
Tel Aviv, Israel
Università di Cagliari
Cagliari, Italy
Ospedale S. Antonio Abate di Gallarate
Gallarate (Varese), Italy
Ospedale S. Luigi Gonzaga
Orbassano (TO), Italy
Universita Degli Studi di Roma "La Sapienza"
Roma, Italy
Unidad de Investigación en Salud
Chihuahua, CHH, Mexico
Medica Sur
Mexico City, DFE, Mexico
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Orbis Medisch Concern
Sittard-Geleen, Netherlands
Centrum Neurologii Klinicznej Sp. Zo.o.
Krakow, Poland
Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Kliniczny Nr1 im. Norberta Barlickiego
Lodz, 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
Institute of Psychiatry and Neurology/Instytut Psychiatrii i Neurologii
Warsaw, Poland
Research Medical Complex "Your Health" Ltd
Kazan', Russia
Moscow State Public Medical Institution Clinical Hospital #11, Neurology Department
Moscow, Russia
Neurology Research Center under the Russian Academy of Medical Sciences
Moscow, Russia
Russian State Medical University, Department of Neurology and Neurosurgery
Moscow, Russia
Municipal Treatment and Prevention Institution, City Hospital #33
Nizhny Novgorod, Russia
Federal State Public Medical Institution: Siberian District Medical Center under the Federal Agency
Novosibirsk, Russia
Municipal Public Medical Institution: City Hospital #2 of Pyatigorsk, Neurology Department
Pyatigorsk, Russia
Institute of Human Brain RAS, Laboratory of Neuroimmunology
Saint Petersburg, Russia
St Petersburg State Pavlov Medical University, Dept of Neurology and Neurosurgery with a Hospital
Saint Petersburg, Russia
St. Petersburg General Hospital #2, Neurology Department #2
Saint Petersburg, Russia
St. Petersburg State Public Medical Institution: Nikolayevskaya Hospital
Saint Petersburg, Russia
Samara Regional Clinical Hospital n.a. Kalinin
Samara, Russia
State Public Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov
Ufa, Russia
Clinical Centre Serbia, Institute of Neurology,Dr.Subotica 6,Belgrade
Belgrade, Serbia
Military Medical Academy, Institute of Neurology
Belgrade, Serbia
Clinical Centre Kragujevac, Clinic of Neurology
Kragujevac, Serbia
Clinical Centre Nis, Clinic of Neurology
Niš, Serbia
Clinical Centre Vojvodina
Novi Sad, Serbia
Hospital Universitario Vall d' Hebron
Barcelona, Spain
Hospital Clínico Universitario San Carlos
Madrid, Spain
Hospital Carlos Haya, Neurology Service
Málaga, Spain
Hospital Virgen Macarena
Seville, Spain
SU/Östra sjukhuset
Gothenburg, Sweden
Norrlands Universitets sjukhus
Umeå, Sweden
Institute of Neurology, Psychiatry and Narcology under the AMS of Ukraine, Dep of Neuroinfection& MS
Kharkiv, Ukraine
Kiev Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System
Kiev, Ukraine
Hospital of Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Dept.
Kiev-21, Ukraine
Lviv National Medical University n.a. Danylo Galytsky, Department of Neurology
Lviv, Ukraine
Frenchay Hospital
Bristol, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
University Hospital of Wales, Dept of Neurology
Cardiff, United Kingdom
Royal London Hospital
London, United Kingdom
Salford Royal NHS Foundation Trust
Salford, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Related Publications (18)
CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
PMID: 18946064BACKGROUNDCohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
PMID: 23122652BACKGROUNDColes AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
PMID: 23122650BACKGROUNDZiemssen T, Bass AD, Van Wijmeersch B, Eichau S, Richter S, Hoffmann F, Armstrong NM, Chirieac M, Cunha-Santos J, Singer BA. Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study. Ther Adv Neurol Disord. 2025 Feb 10;18:17562864241306575. doi: 10.1177/17562864241306575. eCollection 2025.
PMID: 39935588DERIVEDColes AJ, Achiron A, Traboulsee A, Singer BA, Pozzilli C, Oreja-Guevara C, Giovannoni G, Comi G, Freedman MS, Ziemssen T, Shiota D, Rawlings AM, Wong AT, Chirieac M, Montalban X. Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study. Ther Adv Neurol Disord. 2023 Sep 21;16:17562864231194823. doi: 10.1177/17562864231194823. eCollection 2023.
PMID: 37745914DERIVEDDayan CM, Lecumberri B, Muller I, Ganesananthan S, Hunter SF, Selmaj KW, Hartung HP, Havrdova EK, LaGanke CC, Ziemssen T, Van Wijmeersch B, Meuth SG, Margolin DH, Poole EM, Baker DP, Senior PA. Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies. Mult Scler J Exp Transl Clin. 2023 Jan 3;9(1):20552173221142741. doi: 10.1177/20552173221142741. eCollection 2023 Jan-Mar.
PMID: 36619856DERIVEDColes AJ, Jones JL, Vermersch P, Traboulsee A, Bass AD, Boster A, Chan A, Comi G, Fernandez O, Giovannoni G, Kubala Havrdova E, LaGanke C, Montalban X, Oreja-Guevara C, Piehl F, Wiendl H, Ziemssen T. Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data. Mult Scler. 2022 Apr;28(5):842-846. doi: 10.1177/13524585211061335. Epub 2021 Dec 9.
PMID: 34882037DERIVEDKuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, Rӧsch N, Kaiser C, Mitchell CP, Leppert D, Havari E, Kappos L. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS. Mult Scler. 2022 Apr;28(4):573-582. doi: 10.1177/13524585211032348. Epub 2021 Aug 11.
PMID: 34378446DERIVEDColes AJ, Arnold DL, Bass AD, Boster AL, Compston DAS, Fernandez O, Havrdova EK, Nakamura K, Traboulsee A, Ziemssen T, Jacobs A, Margolin DH, Huang X, Daizadeh N, Chirieac MC, Selmaj KW. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134. doi: 10.1177/1756286420982134. eCollection 2021.
PMID: 34035833DERIVEDBass AD, Arroyo R, Boster AL, Boyko AN, Eichau S, Ionete C, Limmroth V, Navas C, Pelletier D, Pozzilli C, Ravenscroft J, Sousa L, Tintore M, Uitdehaag BMJ, Baker DP, Daizadeh N, Choudhry Z, Rog D; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years. Mult Scler Relat Disord. 2021 Apr;49:102717. doi: 10.1016/j.msard.2020.102717. Epub 2020 Dec 24.
PMID: 33476880DERIVEDHorakova D, Boster A, Bertolotto A, Freedman MS, Firmino I, Cavalier SJ, Jacobs AK, Thangavelu K, Daizadeh N, Poole EM, Baker DP, Margolin DH, Ziemssen T; CARE-MS I, CARE-MS II, and CAMMS03409 Investigators. Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years. Mult Scler J Exp Transl Clin. 2020 Dec 18;6(4):2055217320972137. doi: 10.1177/2055217320972137. eCollection 2020 Oct-Dec.
PMID: 33414927DERIVEDZiemssen T, Bass AD, Berkovich R, Comi G, Eichau S, Hobart J, Hunter SF, LaGanke C, Limmroth V, Pelletier D, Pozzilli C, Schippling S, Sousa L, Traboulsee A, Uitdehaag BMJ, Van Wijmeersch B, Choudhry Z, Daizadeh N, Singer BA; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study. CNS Drugs. 2020 Sep;34(9):973-988. doi: 10.1007/s40263-020-00749-x.
PMID: 32710396DERIVEDGilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2020 Jun 15;17(1):189. doi: 10.1186/s12974-020-01847-9.
PMID: 32539719DERIVEDComi G, Alroughani R, Boster AL, Bass AD, Berkovich R, Fernandez O, Kim HJ, Limmroth V, Lycke J, Macdonell RA, Sharrack B, Singer BA, Vermersch P, Wiendl H, Ziemssen T, Jacobs A, Daizadeh N, Rodriguez CE, Traboulsee A; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies. Mult Scler. 2020 Dec;26(14):1866-1876. doi: 10.1177/1352458519888610. Epub 2019 Nov 25.
PMID: 31762387DERIVEDVan Wijmeersch B, Singer BA, Boster A, Broadley S, Fernandez O, Freedman MS, Izquierdo G, Lycke J, Pozzilli C, Sharrack B, Steingo B, Wiendl H, Wray S, Ziemssen T, Chung L, Margolin DH, Thangavelu K, Vermersch P. Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies. Mult Scler. 2020 Nov;26(13):1719-1728. doi: 10.1177/1352458519881759. Epub 2019 Nov 1.
PMID: 31675266DERIVEDOkai AF, Amezcua L, Berkovich RR, Chinea AR, Edwards KR, Steingo B, Walker A, Jacobs AK, Daizadeh N, Williams MJ; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study). Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25.
PMID: 31654272DERIVEDArroyo R, Bury DP, Guo JD, Margolin DH, Melanson M, Daizadeh N, Cella D. Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis. Mult Scler. 2020 Jul;26(8):955-963. doi: 10.1177/1352458519849796. Epub 2019 May 30.
PMID: 31144568DERIVEDHavrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, Schippling S, Selmaj KW, Traboulsee A, Compston DAS, Margolin DH, Thangavelu K, Rodriguez CE, Jody D, Hogan RJ, Xenopoulos P, Panzara MA, Coles AJ; CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12;89(11):1107-1116. doi: 10.1212/WNL.0000000000004313. Epub 2017 Aug 23.
PMID: 28835401DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Trial Transparency Team
- Organization
- Sanofi
Study Officials
- STUDY DIRECTOR
Medical Monitor
Genzyme Coorporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2009
First Posted
June 30, 2009
Study Start
August 1, 2009
Primary Completion
February 1, 2016
Study Completion
February 1, 2016
Last Updated
May 15, 2017
Results First Posted
May 15, 2017
Record last verified: 2017-05