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

Purpose

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:

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.
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.
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.

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Biological: alemtuzumab	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Interferon Interferon Beta-1a Alemtuzumab

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Time to Sustained Accumulation of Disability (SAD) [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]
Relapse Rate [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to sustained reduction in disability (SRD) as measured by the EDSS (Expanded Disability Status Scale) [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]
Change over time in EDSS scores [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]
Change over time in MRI findings [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]
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 [ Time Frame: Prior study baseline through Extension Month 48 ] [ Designated as safety issue: No ]

Enrollment:	1322
Study Start Date:	August 2009
Estimated Study Completion Date:	February 2016
Estimated Primary Completion Date:	February 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Previously treated with alemtuzumab Patients treated with alemtuzumab in prior Genzyme-sponsored studies of alemtuzumab who show documented evidence of resumed disease activity	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)
Experimental: Previously treated with interferon beta-1a (Rebif®) Patients treated with interferon beta-1a (Rebif®) in prior Genzyme-sponsored studies of alemtuzumab who meet treatment eligibility criteria.	Biological: 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.

Detailed 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, but some patients may need additional safety follow-up via a separate mechanism beyond the 48 months.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930553

Show 176 Study Locations

Sponsors and Collaborators

Genzyme

Bayer

Investigators

Study Director:

Medical Monitor

Genzyme Coorporation

More Information

Publications:

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.

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.

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT00930553 History of Changes
Other Study ID Numbers:	CAMMS03409, 2009-010788-18
Study First Received:	June 26, 2009
Last Updated:	February 13, 2013
Health Authority:	United States: Food and Drug Administration Argentina: Ministry of Health Austria: Agency for Health and Food Safety Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Brazil: National Health Surveillance Agency (ANVISA) Canada: Health Canada Croatia: Ministry of Health and Social Care Czech Republic: State Institute for Drug Control Denmark: Danish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Paul-Ehrlich-Institut Israel: Ministry of Health Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Mexico: Federal Commission for Sanitary Risks Protection Netherlands: Medical Ethics Review Committee (METC) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: Ministry of Health of the Russian Federation Serbia and Montenegro: Agency for Drugs and Medicinal Devices Spain: Ministry of Health Sweden: Medical Products Agency Ukraine: State Pharmacological Center - Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genzyme:

Multiple Sclerosis

Additional relevant MeSH terms:

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 beta 1a

Campath 1G
Antibodies, Neoplasm
Alemtuzumab
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 19, 2013