A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis

January 6, 2015 updated by: Genzyme, a Sanofi Company

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

This was a Phase II, randomized, open-label, rater-blinded, three-arm study comparing two different doses of alemtuzumab (Lemtrada™) and one dose of subcutaneous (SC) interferon beta-1a (Rebif®) in participants with early, active relapsing-remitting multiple sclerosis (MS) who had not been previously treated with MS therapies other than steroids. The study was conducted for an initial period of 3 years and a follow-up to 5 years or more.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aims of MS therapy are to prevent the progression of disease and accumulation of long-term disability. The hypothesis underlying this study was that aggressive treatment of inflammation in the brain early in the course of MS would protect the participant from disease progression and accumulating disability.

This protocol compared two different doses of alemtuzumab and high-dose, high frequency of SC interferon beta-1a to evaluate the safety profiles of the respective treatments and to evaluate efficacy in terms of:

  • Slowing the sustained accumulation of disability in participant with MS;
  • Reducing the frequency of relapses experienced by participant with MS; and
  • Reducing the harmful effects of MS on the brain, as assessed by magnetic resonance imaging (MRI)

Participants who received alemtuzumab during the initial 36-month treatment period may have been eligible for re-treatment with alemtuzumab in the extension study CAMMS03409 (NCT00930553) to evaluate:

  • How long the effects of prior alemtuzumab treatment lasted;
  • If additional treatments with alemtuzumab continued to reduce the effects of MS; and
  • What kind of side effects participants experienced upon retreatment with alemtuzumab

Study Type

Interventional

Enrollment (Actual)

334

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Osijek, Croatia
        • Department of Neurology, University Hospital "Osijek"
      • Rijeka, Croatia
        • Department of Neurology, Clinical Hospital Centre "Rijeka"
      • Zagreb, Croatia
        • Department of Neurology, Clinical Hospital Centre "Zagreb"
      • Zagreb, Croatia
        • Department of Neurology, General Hospital "Sveti Duh"
      • Zagreb, Croatia
        • Department of Neurology, University Hopsital "Sestre Milosrdnice"
  • Poland
      • Krakow, Poland
        • Centrum Neurologii Klinicznej
      • Lodz, Poland
        • Samodzielny Publiczny Zakład Opieki Zdrowotnej
      • Lublin, Poland
        • Klinika Neurologii
      • Poznan, Poland
        • Oddzial Kliniczny Neurologii
      • Warszawa, Poland
        • Instytut Psychiatrii i Neurologii
      • Warszawa, Poland
        • Katedra i Klinika Neurologii
  • Russian Federation
      • Moscow, Russian Federation
        • Moscow City Hospital #11
      • Moscow, Russian Federation, 117437
        • Russian State Medical University
      • Moscow, Russian Federation, 125367
        • Neurology Scientific Center RAMS
      • Moscow, Russian Federation
        • Moscow City Hospital #61
      • St. Petersburg, Russian Federation, 197376
        • Institute of Human Brain Ras
      • St. Petersburg, Russian Federation
        • St. Petersburg State Pavlov Medical University
  • United Kingdom
    • England
      • Cambridge, England, United Kingdom
        • Addenbrooke's Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Scottsdale Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Clinical Trials, Inc
    • California
      • Berkeley, California, United States, 94705
        • East Bay Physicians Medical Group
      • Irvine, California, United States, 92618
        • Nerve Pro Research
      • Pasadena, California, United States, 91105
        • Neuro-Therapeutics, Inc.
      • Walnut Creek, California, United States, 938-1343
        • Neurological Research Institute of the East Bay
    • Colorado
      • Denver, Colorado, United States, 80218
        • Neurologic Research Institute/Mile High Research Center
    • Florida
      • Orlando, Florida, United States, 32806
        • Neurological Service of Orlando
      • Pompano Beach, Florida, United States, 33060
        • Neurological Associates/ Research Dept.
      • Sunrise, Florida, United States, 3335-6637
        • Neurology Clinical Research, Inc.
      • Tampa, Florida, United States, 33609
        • Axiom Clinical Research of Florida
    • Georgia
      • Columbus, Georgia, United States, 31909
        • Medical Research and Health Education
    • Illinois
      • Northbrook, Illinois, United States, 60062
        • Consultants in Neurology, Ltd
    • Indiana
      • Fort Wayne, Indiana, United States, 46805
        • Fort Wayne Neurological Center
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Associate in Neurology
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland -Maryland Center for MS
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University Department of Neurology
      • Farmington Hills, Michigan, United States, 48334
        • Michigan Institute for Neurological Disorders
      • Grand Rapids, Michigan, United States, 49525
        • Michigan Medical P.C. Neurology
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester Department of Neurology
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Nevada Neurological Consultants, Ltd.
    • New York
      • Stony Brook, New York, United States, 11794
        • University Hospital an Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • All-Trials Clinical Research, LLC
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74137
        • Neurological Associates of Tulsa, Inc
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103-6296
        • Neurosciencies and Pain Research
    • Tennessee
      • Knoxville, Tennessee, United States, 37934
        • Neurology, PC
    • Texas
      • Houston, Texas, United States
        • Baylor College of Medicine
      • Richardson, Texas, United States, 75080
        • Dallas Neurological Associate
      • Round Rock, Texas, United States, 78681
        • Central Texas Neurology Consultants PA
      • San Antonio, Texas, United States, 78258
        • Neurology Center of San Antonio
      • San Antonio, Texas, United States, 78231
        • Integra Clinical Research, Llc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent form (ICF)
  • Male or non-pregnant, non-lactating female participants, 18 to 50 years of age (inclusive) as of signing the ICF
  • Diagnosis of MS per McDonald's update of the Poser criteria, including cranial MRI consistent with those criteria (McDonald, 2001, Ann Neurol)
  • Onset of first MS symptoms within 3 years prior to Screening as of signing the ICF
  • Expanded Disability Status Scale (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 (that is, the initial event if within 2 years of study entry plus at least 1 relapse, or at least 2 relapses if the initial event was between 2 and 3 years prior to study entry)
  • In addition to the clinical criteria, at least 1 enhancing lesion on any 1 of up to 4 screening gadolinium-enhanced MRI brain 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 (IVIG), glatiramer acetate, and mitoxantrone
  • Personal history of thyroid autoimmune disease
  • Personal history of clinically significant autoimmune disease (for example, inflammatory bowel disease, diabetes, lupus, severe asthma)
  • History of thyroid carcinoma (previous thyroid adenoma was acceptable and was not considered an exclusion criterion)
  • History of malignancy (except for basal cell skin carcinoma if disease-free for at least 5 years)
  • Any disability acquired from trauma or another illness that, in the opinion of the Investigator, interfered with evaluation of disability due to MS
  • Previous treatment with alemtuzumab
  • History of anaphylaxis following exposure to humanized monoclonal antibodies
  • Inability to undergo MRI with gadolinium administration
  • Female participants of childbearing potential with a positive serum pregnancy test at screening or Baseline
  • Male and female participants who did not agree to use effective contraceptive method(s) during the study
  • Impaired renal function (that is, serum creatinine greater than or equal to 2 times the upper limit of normal [ULN])
  • Untreated, major depressive disorder
  • Epileptic seizures that were not adequately controlled by treatment
  • Suicidal ideation
  • Major systemic disease or other illness that, in the opinion of the Investigator, have compromised participant safety or interfered with the interpretation of study results
  • Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-thyroid stimulating hormone (TSH) receptor antibodies; known seropositivity for human immunodeficiency (HIV)
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
  • Presence of a monoclonal paraprotein
  • Participants who had any form of MS other than relapsing-remitting
  • Participants currently participating in a clinical study of an experimental or unapproved/unlicensed therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Interferon Beta-1a
Biological: Interferon beta-1a
Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 36 months.
Other Names:
  • Rebif®
Experimental: Alemtuzumab 12 mg
Biological: Alemtuzumab 12 mg
Alemtuzumab 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ [CD4+] T-cell count was >=100*10^6 cells per liter).
Other Names:
  • Lemtrada
Experimental: Alemtuzumab 24 mg
Biological: Alemtuzumab 24 mg
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Other Names:
  • Lemtrada

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability of Participants With Sustained Accumulation of Disability (SAD)
Time Frame: Up to 3 years
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) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
Up to 3 years
Annualized Relapse Rate
Time Frame: Up to 3 years
Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment
Time Frame: Year 3
Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.
Year 3
Percent Change From Baseline in T1 Cerebral Volume at Year 3
Time Frame: Baseline, Year 3
Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100*([brain volume at Year 3] minus [brain volume at Baseline]) divided by [brain volume at Baseline]).
Baseline, Year 3
Percent Change From Baseline in MRI T2 Lesion Volume at Year 3
Time Frame: Baseline, Year 3
Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100*([lesion volume at Year 3] minus [lesion volume at Baseline]) divided by [lesion volume at Baseline]).
Baseline, Year 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Collaborators

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

December 19, 2002

First Submitted That Met QC Criteria

December 20, 2002

First Posted (Estimate)

December 23, 2002

Study Record Updates

Last Update Posted (Estimate)

January 8, 2015

Last Update Submitted That Met QC Criteria

January 6, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAMMS223

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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