An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

Official title:

An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00930553
• Other study ID #: CAMMS03409
• Secondary ID: 2009-010788-18LT
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2009
• Last updated: March 11, 2016
• Start date: August 2009
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Ministry of HealthAustria: Agency for Health and Food SafetyAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance Agency (ANVISA)Canada: Health CanadaCroatia: Ministry of Health and Social CareCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutIsrael: Ministry of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionNetherlands: Medical Ethics Review Committee (METC)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSpain: Ministry of HealthSweden: Medical Products AgencyUkraine: State Pharmacological Center - Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This open-label, rater-blinded extension study will enroll patients who have 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 are:

1. To examine the long term safety and efficacy of alemtuzumab treatment in patients 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 patients who received Rebif® (interferon beta-1a) as their study treatment in one of the prior studies.

3. To determine if and when further alemtuzumab treatment is needed, and the safety and efficacy of this "as needed" treatment. This applies both to patients who received alemtuzumab for the first time in one of the prior studies or for the first time in this extension study.

Description:

Alemtuzumab treatment will either be on a fixed schedule of two treatment cycles a year apart for patients 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 MS activity) for patients who have already completed a fixed schedule of treatment with alemtuzumab in one of the prior Genzyme-sponsored studies. There is no comparison treatment in this study. All patients will be required to return to their study site every 3 months for neurologic and other assessments. In addition, safety-related laboratory tests and surveys will be performed at least monthly. Participation in the extension study will last 48 months from enrollment. Study duration may be extended per protocol amendments to allow patients to remain in the study through the time of drug approval or until a long term follow up study is available in each respective country.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1322
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and have 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 have 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 mean that patients 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 are not eligible for inclusion in the Extension Study. Patients who enrolled in CAMMS324 after participation in CAMMS223 must meet criteria 1 or 2 to be eligible for inclusion in the Extension Study.

Exclusion Criteria:

• Any alemtuzumab patient from CAMMS223, CAMMS323, or CAMMS324 who has received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies), or is participating in any other investigational study, unless approved by Genzyme. In addition, these patients must be screened for disqualifying safety concerns before receiving alemtuzumab retreatment.

• Any Rebif® patient from CAMMS223, CAMMS323, or CAMMS324 who meets any of the following criteria. In addition, these patients must be screened for disqualifying safety concerns before receiving alemtuzumab treatment. a)Does not wish to receive alemtuzumab; b) Ongoing participation in any other investigational study, unless approved by Genzyme; c)Has 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 patients only).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Biological:
• alemtuzumab
12 mg per day administered through IV, once a day for 3 consecutive days (patients may receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period)
• 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. Patients may 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.

Locations

Country	Name	City	State
Argentina	DIABAID	Buenos Aires
Australia	The Wesley Research Institute	Auchenflower QLD
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Gold Coast Hospital	Southport	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville, SA
Austria	AKH Wien-Universitätskliniken für Neurologie	Vienna
Belgium	Cliniques Universitaires Saint-luc	Brussel
Belgium	CHU Ourthe Amblève	Esneux
Belgium	University Hospital Leuven, Campus Gasthuisberg	Leuven
Brazil	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
Canada	University of Calgary, Department of Neurology	Calgary	Alberta
Canada	Clinique Neuro-Outaouais	Gatineau	Quebec
Canada	Recherche Sepmus, Inc.	Greenfield Park	Quebec
Canada	Kingston General Hospital MS Clinic	Kingston	Ontario
Canada	London Health Sciences Centre - University Hospital	London, ON
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	The Ottawa Hospital - MS Research	Ottawa, Ontario
Canada	University of British Columbia	Vancouver, BC
Croatia	Clinical Hospital Osijek	Osijek
Croatia	Clinical Hospital Centre Rijeka	Rijeka
Croatia	General Hospital Varazdin, Department for Neurology	Varazdin
Croatia	Clinical Hospital Centre "Sestre Milosrdnice"	Zagreb
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Croatia	Clinical Hospital Sveti Duh	Zagreb
Czech Republic	St. Anne's University Hospital Brno	Brno
Czech Republic	University Hospital Hradec Králové	Hradec Kralove
Czech Republic	General Hospital, 128 21 Praha 2	Prague
Czech Republic	Hospital Teplice, Neurology Department, MS centrum	Teplice
Denmark	Aarhus Sygehus	Århus C
Denmark	Rigshospitalet Department of Neurology	Copenhagen
France	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	Hôpital Civil	Strasbourg Cedex
France	CHU de Toulouse, Hôpital Purpan	Toulouse Cedex 9
Germany	Jüdisches Krankenhaus Berlin	Berlin-Mitte
Germany	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	Hannover
Germany	Oberhavel Klinicum GmbH - Krankenhaus Hennigsdorf	Hennigsdorf
Germany	Klinikum Ingolstadt	Ingolstadt
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
Israel	Hadassah Medical Center Ein Karem	Ein Karem, Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Sourasky Tel Aviv Medical Center	Tel Aviv
Italy	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
Mexico	Unidad de Investigación en Salud	Chihuahua, CHH
Mexico	Medica Sur	Mexico City, DFE
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Orbis Medisch Concern	Sittard-Geleen
Poland	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
Russian Federation	Research Medical Complex "Your Health" Ltd	Kazan
Russian Federation	Moscow State Public Medical Institution Clinical Hospital #11, Neurology Department	Moscow
Russian Federation	Neurology Research Center under the Russian Academy of Medical Sciences	Moscow
Russian Federation	Russian State Medical University, Department of Neurology and Neurosurgery	Moscow
Russian Federation	Municipal Treatment and Prevention Institution, City Hospital #33	Nizhny Novgorod
Russian Federation	Federal State Public Medical Institution: Siberian District Medical Center under the Federal Agency	Novosibirsk
Russian Federation	Municipal Public Medical Institution: City Hospital #2 of Pyatigorsk, Neurology Department	Pyatigorsk
Russian Federation	Samara Regional Clinical Hospital n.a. Kalinin	Samara
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 General Hospital #2, Neurology Department #2	St. Petersburg
Russian Federation	St. Petersburg State Public Medical Institution: Nikolayevskaya Hospital	St. Petersburg
Russian Federation	State Public Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov	Ufa
Serbia	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	Nis
Serbia	Clinical Centre Vojvodina	Novi Sad
Spain	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
Sweden	SU/Östra sjukhuset	Göteborg
Sweden	Norrlands Universitets sjukhus	Umeå
Ukraine	Institute of Neurology, Psychiatry and Narcology under the AMS of Ukraine, Dep of Neuroinfection& MS	Kharkov
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
United Kingdom	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 States	University of New Mexico, Dept. of Neurology	Albuquerque	New Mexico
United States	Lehigh Valley Hospital Neurosciences and Pain Research	Allentown	Pennsylvania
United States	University of Michigan Medical School	Ann Arbor	Michigan
United States	Emory University Department of Neurology	Atlanta	Georgia
United States	Shepherd Center Multiple Sclerosis Institute	Atlanta	Georgia
United States	University of Colorado Health Science Center - Aurora	Aurora	Colorado
United States	University of Maryland, Maryland Center for MS	Baltimore	Maryland
United States	East Bay Physicians Medical Group/ Sutter East Bay Medical Foundation	Berkeley	California
United States	The MS Center at St. Elizabeth's	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Michigan Neurology Association	Clinton Twp	Michigan
United States	Neurology Clinic PC	Cordova	Tennessee
United States	North Central Neurology Associates, P.C.	Cullman	Alabama
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	Wayne State University, The School of Medicine, Department of Neurology	Detroit	Michigan
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Advanced Neurosciences Institute	Franklin	Tennessee
United States	Advanced Neurology of Colorado	Ft. Collins	Colorado
United States	Spectrum Health Medical Group, Neurology/Michigan Medical P.C., West Michigan MS Clinic	Grand Rapids	Michigan
United States	Baylor College of Medicine, Maxine Mesinger MS Clinic	Houston	Texas
United States	Indiana University Multiple Sclerosis Center	Indianapolis	Indiana
United States	University of Florida Neuroscience Institute	Jacksonville	Florida
United States	Saint Luke's Brain & Stroke Institute	Kansas City	Missouri
United States	University of Kansas Medical Center, Department of Neurology	Kansas City	Kansas
United States	Hope Neurology	Knoxville	Tennessee
United States	Neurology Center North Orange County	La Habra	California
United States	Empire Neurology P.C.	Latham	New York
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	MidAmerica Neuroscience Institute	Lenexa	Kansas
United States	Associates in Neurology, P.S.C.	Lexington	Kentucky
United States	University of Southern California Keck School of Medicine/University of Southern California LAC & USC Medical Center	Los Angeles	California
United States	Kentucky Neuroscience Research	Louisville	Kentucky
United States	Neurology Associates, P.A.	Maitland	Florida
United States	Winthrop University Hospital Multiple Sclerosis Treatment Center	Mineola	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale MS Research Center	New Haven	Connecticut
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	Consultants in Neurology, LTD	Northbrook	Illinois
United States	OMRF Multiple Sclerosis Center of Excellence	Oklahoma City	Oklahoma
United States	Neuro-Therapeutics, Inc.	Pasadena	California
United States	South Shore Neurologic Associates, P.C.	Patchogue	New York
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	Neurological Associates	Pompano Beach	Florida
United States	Rhode Island Hospital MS Center - The Neurology Foundation, Inc	Providence	Rhode Island
United States	Renown Institute for Neurosciences	Reno	Nevada
United States	Rochester Multiple Sclerosis Center	Rochester	New York
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	Negroski, Stein, Sutherland and Hanes Neurology	Sarasota	Florida
United States	Mayo Clinic Arizona (Scottsdale)	Scottsdale	Arizona
United States	Swedish Medical MS Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	SUNY Upstate Medical University, Department of Neurology	Syracuse	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	University of South Florida College of Medicine	Tampa	Florida
United States	MS Center at Holy Name Hospital	Teaneck	New Jersey
United States	Northern Michigan Neurology	Traverse City	Michigan
United States	Northwest NeuroSpecialists, PLLC	Tucson	Arizona
United States	Oak Clinic for Multiple Sclerosis	Uniontown	Ohio
United States	MS Center of Greater Washington	Vienna	Virginia
United States	The George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Wake Forest University Health Science Department of Neurology	Winston Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  Czech Republic,  Denmark,  France,  Germany,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Russian Federation,  Serbia,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (3)

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. — View Citation

Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. Epub 2005 Jul 27. — View Citation

Fox E, Sullivan H, Gazda S. Open label, single-arm, Phase II study of alemtuzumab in patients with active relapsing-remitting multiple sclerosis who have failed licensed beta-interferon therapies. Poster presentation P06.07 at the 59th Annual Meeting of the American Academy of Neurology (AAN) on 03 May 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Sustained Accumulation of Disability (SAD)		Prior study baseline through Extension Month 48	No
Primary	Relapse Rate		Prior study baseline through Extension Month 48	No
Secondary	Time to sustained reduction in disability (SRD) as measured by the EDSS (Expanded Disability Status Scale)		Prior study baseline through Extension Month 48	No
Secondary	Change over time in EDSS scores		Prior study baseline through Extension Month 48	No
Secondary	Change over time in MRI findings		Prior study baseline through Extension Month 48	No
Secondary	Change over time in self-reported quality of life as assessed by the Medical Outcome Study SF-36 Version 2, FAMS (Functional Assessment of Multiple Sclerosis), and EQ-5D findings		Prior study baseline through Extension Month 48	No