Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two - Full Text View

Sponsor:	Genzyme
Collaborator:	Bayer
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00548405

Purpose

The purpose of this study is to establish the efficacy and safety of two different doses of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enroll patients who have received an adequate trial of disease-modifying therapies but continued to relapse while being treated, and who meet a minimum severity of disease as measured by magnetic resonance imaging (MRI). Patients will have monthly laboratory tests and comprehensive testing every 3 months.

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Biological: alemtuzumab Biological: interferon beta-1a (Rebif®)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase 3 Randomized, Rater- and Dose-Blinded Study Comparing 2 Annual Cycles of IV 12 mg and 24 mg Alemtuzumab to 3x Weekly SC Interferon Beta-1a (Rebif®) in Relapsing-Remitting Multiple Sclerosis Patients Who Have Relapsed on Therapy

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Interferon beta Interferon-beta Campath Interferon beta 1a Alemtuzumab Interferons

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Change from baseline in EDSS (Expanded Disability Status Scale) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	840
Study Start Date:	October 2007
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
alemtuzumab 12 mg: Experimental	Biological: alemtuzumab 12 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 12 mg per day administered through IV, once a day for 3 consecutive days at Month 12
alemtuzumab 24mg: Experimental	Biological: alemtuzumab 24 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 24 mg per day administered through IV, once a day for 3 consecutive days at Month 12 Note: The 24 mg alemtuzumab dose is closed to enrollment.
interferon beta-1a (Rebif ®): Active Comparator	Biological: interferon beta-1a (Rebif®) 44 mcg administered 3-times weekly by SC injections for 2 years

Detailed Description:

Every patient will receive active treatment; there is no placebo. The 24 mg alemtuzumab dose is closed to enrollment so newly enrolled patients will be randomly assigned to treatment with either 12 mg alemtuzumab or Rebif® at a 2:1 ratio (ie, 2 given 12 mg or 24 mg alemtuzumab for every 1 given Rebif®). Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif® will be self-injected 3 times per week for 2 years. All patients will be required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests will be performed at least monthly. Participation in this study will end 2 years after the start of treatment for each patient. Additionally, all patients who receive alemtuzumab will be followed in the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab in an Extension Study.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of MS and MRI scan demonstrating white matter lesions attributable to MS
Onset of MS symptoms within 10 years
EDSS score 0.0 to 5.0
≥2 MS attacks within 24 months, with ≥1 attack within 12 months
≥1 MS attack (relapse)during treatment with a beta interferon therapy or glatiramer acetate after having been on that therapy for at least 6 months within 10 years

Exclusion Criteria:

Previous treatment with alemtuzumab
Previous treatment with any investigational drug (i.e. a medication that is not approved at any dose or for any indication)
Treatment with natalizumab, methotrexate, azothioprine or cyclosporine in the past 6 months
Previous treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab, or any other immunosuppressive, or cytotoxic therapy (other than steroid treatment)
Any progressive form of MS
Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS
Major systemic disease that cannot be treated or adequately controlled by therapy
Active infection or high risk for infection
Autoimmune disorder (other than MS)
Impaired hepatic or renal function
History of malignancy, except basal skin cell carcinoma
Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
Known bleeding disorder
Of childbearing potential with a positive serum pregnancy test, pregnant, or lactating
Current participation in another clinical study or previous participation in CAMMS323 (NCT00530348)
Previous hypersensitivity reaction to any immunoglobulin product
Known allergy or intolerance to interferon beta, human albumin, or mannitol
Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver
Inability to undergo MRI with gadolinium administration
Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548405

Show 181 Study Locations

Sponsors and Collaborators

Genzyme

Bayer

Investigators

Study Director:

Medical Monitor

Genzyme Coorporation

More Information

Publications:

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.

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.

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.

Responsible Party:	Genzyme Corporation ( Medical Monitor )
ClinicalTrials.gov Identifier:	NCT00548405 History of Changes
Other Study ID Numbers:	CAMMS32400507, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Study First Received:	October 22, 2007
Last Updated:	July 9, 2010
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; Australia: Department of Health and Ageing Therapeutic Goods Administration; Czech Republic: State Institute for Drug Control; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Sweden: Medical Products Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency; France: Afssaps - French Health Products Safety Agency; Germany: Paul-Ehrlich-Institut; Russia: Ministry of Health and Social Development of the Russian Federation; Ukraine: State Pharmacological Center - Ministry of Health; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Mexico: Federal Commission for Sanitary Risks Protection; Brazil: National Health Surveillance Agency; Italy: The Italian Medicines Agency; Netherlands: Medical Ethics Review Committee (METC); Spain: Spanish Agency of Medicines; Belgium: Federal Agency for Medicinal Products and Health Products; Switzerland: Swissmedic; Austria: Federal Ministry for Health Family and Youth; Denmark: Danish Medicines Agency; Israel: Ministry of Health; Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Genzyme:

Multiple Sclerosis

Additional relevant MeSH terms:

Campath 1G
Alemtuzumab
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferon Type I, Recombinant
Interferons

Interferon beta 1a
Antibodies, Monoclonal
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Adjuvants, Immunologic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 01, 2010