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A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
This study is ongoing, but not recruiting participants.
First Received: December 19, 2002   Last Updated: July 13, 2009   History of Changes
Sponsor: Genzyme
Collaborator: Bayer
Information provided by: Genzyme
ClinicalTrials.gov Identifier: NCT00050778
  Purpose

This is a Phase II, randomized, open-label, three-arm study comparing two different doses of alemtuzumab and Rebif® in patients with early, active relapsing-remitting Multiple Sclerosis (MS) who have not been previously treated with MS therapies other than steroids.


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

Study Type: Interventional
Study Design: Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase II, Randomized, Open-Label, Three-Arm Study Comparing Low- and High Dose Alemtuzumab and High-Dose Subcutaneous Interferon Beta-1a (Rebif®) in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Genzyme:

Primary Outcome Measures:
  • Sustained Accumulation of Disability (SAD), Confirmed Through 6 Months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Patients Who Are Relapse Free at 3 Years After Initial Treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Magnetic Resonance Imaging (MRI) T1 to Determine Rate of Cerebral Atrophy (Decrease in Cerebral Volume) as Seen on MRI Brain Scan at 3 Years After Initial Treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Change in MRI T2 Lesion Volume at 3 Years After Initial Treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 334
Study Start Date: December 2002
Estimated Study Completion Date: June 2013
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator Biological: interferon beta-1a (Rebif®)
44 mcg administered 3-times weekly by SC injections for 36 months.
2: 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; optional re-treatment at Month 24 depending on investigator discretion and laboratory assessments.

After initial 36-month treatment period, eligible consenting patients will receive re-treatment on either a fixed schedule (2 annual cycles of 12 mg per day for 3 consecutive days) or an as-needed schedule (up to 2 cycles at least 12 months apart of 12 mg per day for 3 consecutive days only upon MS relapse or new brain abnormalities on MRI)

3: 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; optional re-treatment at Month 24 depending on investigator discretion and laboratory assessments.

After the initial 36-month treatment period, eligible consenting patients will receive retreatment on either a fixed schedule (2 annual cycles of 12 mg per day for 3 consecutive days) or an as-needed schedule (up to 2 cycles at least 12 months apart of 12 mg per day for 3 consecutive days only upon MS relapse or new brain abnormalities on MRI)


Detailed Description:

The aims of treatment for multiple sclerosis (MS) therapy are to prevent the progression of disease and accumulation of long-term disability. The hypothesis underlying this study is that aggressive treatment of inflammation in the brain early in the course of MS will protect the patient from disease progression and accumulating disability.

This protocol compares two different doses of alemtuzumab and Rebif® to evaluate the kind of side effects that patients experience and to evaluate wich drug is better at:

  • Slowing the sustained accumulation of disability in patients with MS
  • Reducing the frequency of relapses that patients with MS experience);
  • Reducing the effects of MS on the brain, as assessed by magnetic resonance imaging (MRI)

Patients who receive alemtuzumab during the initial 36-month treatment period may be eligible for additional alemtuzumab retreatment on either a fixed or an as-needed schedule to evaluate:

  • How long the effects of prior alemtuzumab treatment last;
  • If additional treatments with alemtuzumab continue to reduce the effects of MS; and
  • What kind of side effects patients experience once patients begin taking alemtuzumab again
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent form.
  • Male or non-pregnant, non-lactating female patients, 18 to 50 years of age (inclusive).
  • Diagnosis of MS per McDonald's update of the Poser criteria, including cranial MRI consistent with those criteria.
  • Onset of first MS symptoms within 3 years prior to screening.
  • EDSS score 0.0 to 3.0 (inclusive) at the screening and baseline visits.
  • At least 2 completed clinical episodes of MS in the 2 years prior to study entry (ie, the initial event if within 2 years of study entry plus ≥1 relapse, or ≥2 relapses if the initial event was between 2 and 3 years prior to study entry).
  • In addition to the clinical criteria (3 to 6 above), ≥1 enhancing lesion on any 1 of the up to 4 screening gadolinium-enhanced MRI scans during a maximum 3-month run-in period (inclusive of the Month 0 baseline scan).

Exclusion Criteria:

  • Previous immunotherapy for MS other than steroids, including treatment with interferons, intravenous immunoglobulin, glatiramer acetate, and mitoxantrone.
  • Personal history of thyroid autoimmune disease.
  • Personal history of clinically significant autoimmune disease (eg, inflammatory bowel disease, diabetes, lupus, severe asthma).
  • History of thyroid carcinoma (previous thyroid adenoma is acceptable and is not to be considered an exclusion criterion).
  • History of malignancy (except for basal cell skin carcinoma in which situation the patient is eligible only if disease-free for more or equal to 5 years).
  • Any disability acquired from trauma or another illness that, in the opinion of the investigator, could interfere with evaluation of disability due to MS.
  • Previous treatment with CAMPATH.
  • History of anaphylaxis following exposure to humanized monoclonal antibodies.
  • Inability to undergo MRI with gadolinium administration.
  • Female patients with childbearing potential with a positive serum pregnancy test at screening or baseline. (NB: Serum pregnancy testing will be performed on each occasion.).
  • Male and female patients who do not agree to use effective contraceptive method(s) during the study.
  • Impaired renal function (ie, serum creatinine larger or equal to 2 times the Institutional upper limit of normal [ULN]).
  • Untreated, major depressive disorder (MDD).
  • Epileptic seizures that are not adequately controlled by treatment.
  • Suicidal ideation.
  • Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results.
  • Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-TSH receptor antibodies; known seropositivity for HIV.
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis.
  • Presence of a monoclonal paraprotein.
  • Patients who, in the opinion of the investigator, have any form of MS other than relapsing-remitting
  • Patients currently participating in a clinical trial of an experimental or unapproved/unlicensed therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00050778

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
United States, Arkansas
Clinical Trials, Inc
Little Rock, Arkansas, United States, 72205
United States, California
Multiple Sclerosis Service
Walnut Creek, California, United States, 94596
East Bay Region Associates in Neurology
Berkeley, California, United States, 94705
Neuro-Therapeutics, Inc.
Pasadena, California, United States, 91105
Nerve Pro Research
Irvine, California, United States, 92618
United States, Colorado
Colorado Neurology & Headache Center
Denver, Colorado, United States, 80218
United States, Florida
Tampa Neurology Associates
Tampa, Florida, United States, 33609
Neurological Services of Orlando
Orlando, Florida, United States, 32806
Neurological Associates
Sunrise, Florida, United States, 33351
United States, Georgia
Sleep Medicine and Neurology
Columbus, Georgia, United States, 31901
Medical Research & Health Education Foundation
Columbus, Georgia, United States, 31909
United States, Illinois
Consultants in Neurology, Ltd.
Northbrook, Illinois, United States, 60062
United States, Indiana
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States, 46805
United States, Kentucky
Associates in Neurology, P.S.C.
Lexington, Kentucky, United States, 40503
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
Michigan Medical P.C. , West Michigan MS Clinic
Grand Rapids, Michigan, United States, 49525
Wayne State University, The School of Medicine, Dept of Neurology
Detroit, Michigan, United States, 48201
Michigan Institute for Neurological Disorders
Farmington, Michigan, United States, 48334
United States, Minnesota
Mayo Clinic and Foundation
Rochester, Minnesota, United States, 55905
United States, Nevada
Nevada Neurological Consultants
Henderson, Nevada, United States, 89052
United States, New York
University Hospital Stony Brook
Stony Brook, New York, United States, 11794
United States, North Carolina
Triad Neurology Services
Winston-Salem, North Carolina, United States, 27103
United States, Oklahoma
Neurological Associates of Tulsa, Inc.
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Neurosciences Research, MS Center
Allentown, Pennsylvania, United States, 18103
United States, Tennessee
Knoxville Neurology Associates, Baptist Hospital
Knoxville, Tennessee, United States, 37920
United States, Texas
Central Texas Neurology Consultants
Austin, Texas, United States, 78681
Neurology Center of San Antonio
San Antonio, Texas, United States, 78212
Dallas Neurological Associates
Richardson, Texas, United States, 75080
Baylor College of Medicine, Dept. of Neurology
Houston, Texas, United States
Integra Clinical Research, LLC
San Antonio, Texas, United States, 78229
Croatia
Zagreb, Croatia
Rijeka, Croatia
Osijek, Croatia
Poland
Lodz, Poland
Krakow, Poland
Lublin, Poland
Poznan, Poland
Warsaw, Poland
Russian Federation
Moscow, Russian Federation
St. Petersburg, Russian Federation
United Kingdom, England
Cambridge, England, United Kingdom
Sponsors and Collaborators
Genzyme
Bayer
Investigators
Study Director: Medical Monitor Genzyme
  More Information

Additional Information:
Publications:
Responsible Party: Genzyme Corporation ( Medical Monitor )
Study ID Numbers: CAMMS223
Study First Received: December 19, 2002
Results First Received: November 3, 2008
Last Updated: July 13, 2009
ClinicalTrials.gov Identifier: NCT00050778     History of Changes
Health Authority: United States: Food and Drug Administration;   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   Croatia: Ministry of Health and Social Care;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Russia: Ministry of Health and Social Development of the Russian Federation

Keywords provided by Genzyme:
Multiple Sclerosis
Active Relapsing-Remitting Multiple Sclerosis

Additional relevant MeSH terms:
Anti-Infective Agents
Autoimmune Diseases
Immunologic Factors
Demyelinating Diseases
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Nervous System Diseases
Interferons
Adjuvants, Immunologic
Interferon-beta
Sclerosis
Antiviral Agents
Multiple Sclerosis, Relapsing-Remitting
Pharmacologic Actions
Multiple Sclerosis
Pathologic Processes
Therapeutic Uses
Alemtuzumab
Interferon beta 1a
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on November 30, 2009