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Multiple Sclerosis, Relapsing-RemittingPhase 2NCT00050778

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

A Phase 2 study testing Interferon beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg in people with Multiple Sclerosis, Relapsing-Remitting, run by Genzyme, a Sanofi Company at 49 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Multiple Sclerosis, Relapsing-Remitting
What is being tested?
Interferon beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
334 participants
Where
49 sitesin 5 countries
Study dates
Dec 2002to Jan 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

49 sites in 5 countries.

49 sites in 5 countries

United States31 sites

  • Neurosciencies and Pain Research

    Allentown, Pennsylvania, 18103-6296

  • University of Maryland -Maryland Center for MS

    Baltimore, Maryland, 21201

  • East Bay Physicians Medical Group

    Berkeley, California, 94705

  • Medical Research and Health Education

    Columbus, Georgia, 31909

  • Neurologic Research Institute/Mile High Research Center

    Denver, Colorado, 80218

  • Wayne State University Department of Neurology

    Detroit, Michigan, 48201

  • Michigan Institute for Neurological Disorders

    Farmington Hills, Michigan, 48334

  • Fort Wayne Neurological Center

    Fort Wayne, Indiana, 46805

  • Michigan Medical P.C. Neurology

    Grand Rapids, Michigan, 49525

  • Baylor College of Medicine

    Houston, Texas

  • Nerve Pro Research

    Irvine, California, 92618

  • Neurology, PC

    Knoxville, Tennessee, 37934

  • Nevada Neurological Consultants, Ltd.

    Las Vegas, Nevada, 89102

  • Associate in Neurology

    Lexington, Kentucky, 40503

  • Clinical Trials, Inc

    Little Rock, Arkansas, 72205

  • Consultants in Neurology, Ltd

    Northbrook, Illinois, 60062

  • Neurological Service of Orlando

    Orlando, Florida, 32806

  • Neuro-Therapeutics, Inc.

    Pasadena, California, 91105

  • Neurological Associates/ Research Dept.

    Pompano Beach, Florida, 33060

  • Dallas Neurological Associate

    Richardson, Texas, 75080

  • Mayo Clinic Rochester Department of Neurology

    Rochester, Minnesota, 55905

  • Central Texas Neurology Consultants PA

    Round Rock, Texas, 78681

  • Integra Clinical Research, LLC

    San Antonio, Texas, 78231

  • Neurology Center of San Antonio

    San Antonio, Texas, 78258

  • Mayo Clinic Scottsdale Arizona

    Scottsdale, Arizona, 85259

  • University Hospital an Medical Center

    Stony Brook, New York, 11794

  • Neurology Clinical Research, Inc.

    Sunrise, Florida, 3335-6637

  • Axiom Clinical Research of Florida

    Tampa, Florida, 33609

  • Neurological Associates of Tulsa, Inc

    Tulsa, Oklahoma, 74137

  • Neurological Research Institute of the East Bay

    Walnut Creek, California, 938-1343

  • ALL-Trials Clinical Research, LLC

    Winston-Salem, North Carolina, 27103

Other trials in United States

Poland6 sites

  • Centrum Neurologii Klinicznej

    Krakow

  • Samodzielny Publiczny Zakład Opieki Zdrowotnej

    Lodz

  • Klinika Neurologii

    Lublin

  • Oddzial Kliniczny Neurologii

    Poznan

  • Instytut Psychiatrii i Neurologii

    Warsaw

  • Katedra i Klinika Neurologii

    Warsaw

Other trials in Poland

Russia6 sites

  • Russian State Medical University

    Moscow, 117437

  • Neurology Scientific Center RAMS

    Moscow, 125367

  • Moscow City Hospital #11

    Moscow

  • Moscow City Hospital #61

    Moscow

  • Institute of Human brain RAS

    Saint Petersburg, 197376

  • St. Petersburg State Pavlov Medical University

    Saint Petersburg

Other trials in Russia

Croatia5 sites

  • Department of Neurology, University Hospital "Osijek"

    Osijek

  • Department of Neurology, Clinical Hospital Centre "Rijeka"

    Rijeka

  • Department of Neurology, Clinical Hospital Centre "Zagreb"

    Zagreb

  • Department of Neurology, General Hospital "Sveti Duh"

    Zagreb

  • Department of Neurology, University Hopsital "Sestre Milosrdnice"

    Zagreb

Other trials in Croatia

United Kingdom1 site

  • Addenbrooke's Hospital

    Cambridge, England

Other trials in United Kingdom

About this 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

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.

Read the 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
Being tested
Interferon beta-1a, Alemtuzumab 12 mg, Alemtuzumab 24 mg
Keywords
Multiple Sclerosis, Active Relapsing-Remitting Multiple Sclerosis
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interferon beta-1aBiological

    Also called Rebif®

    Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 36 months.

  • Alemtuzumab 12 mgBiological

    Also called Lemtrada

    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).

  • Alemtuzumab 24 mgBiological

    Also called Lemtrada

    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).

Study groups in NCT00050778
Study groupRoleWhat they receive
Interferon Beta-1aActive comparatorNot described
Receives: Biological: Interferon beta-1a
Alemtuzumab 12 mgExperimentalNot described
Receives: Biological: Alemtuzumab 12 mg
Alemtuzumab 24 mgExperimentalNot described
Receives: Biological: Alemtuzumab 24 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Probability of Participants With Sustained Accumulation of Disability (SAD)

    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.

    Measured: Up to 3 years

  2. Annualized Relapse Rate

    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.

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment

    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.

    Measured: Year 3

  2. Percent Change From Baseline in T1 Cerebral Volume at 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]).

    Measured: Baseline, Year 3

  3. Percent Change From Baseline in MRI T2 Lesion Volume at 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]).

    Measured: Baseline, Year 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2002 (estimated)
  2. Study startDec 2002
  3. Primary completionSep 2007
  4. Study completionJan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
334 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00050778
Sponsor's protocol ID
CAMMS223
Status last verified
Jan 2015
First submitted
19 Dec 2002
Last updated
8 Jan 2015
Data monitoring committee
Yes

Publications

  • 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. doi: 10.1007/s00415-005-0934-5. Epub 2005 Jul 27.

    PubMed 16044212

  • 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.

    PubMed 18946064

  • Daniels GH, Vladic A, Brinar V, Zavalishin I, Valente W, Oyuela P, Palmer J, Margolin DH, Hollenstein J. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab. 2014 Jan;99(1):80-9. doi: 10.1210/jc.2013-2201. Epub 2013 Dec 20.

    PubMed 24170099

  • Graves J, Galetta SL, Palmer J, Margolin DH, Rizzo M, Bilbruck J, Balcer LJ. Alemtuzumab improves contrast sensitivity in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2013 Sep;19(10):1302-9. doi: 10.1177/1352458513475722. Epub 2013 Mar 4.

    PubMed 23459567

  • Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3;78(14):1069-78. doi: 10.1212/WNL.0b013e31824e8ee7. Epub 2012 Mar 21.

    PubMed 22442431

  • Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011 Apr;10(4):338-48. doi: 10.1016/S1474-4422(11)70020-5.

    PubMed 21397567

  • Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, Lake SL, Palmer J, Thompson SJ, Wilkins A, Webber DJ, Compston DA, Coles AJ. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010 Aug;133(Pt 8):2232-47. doi: 10.1093/brain/awq176. Epub 2010 Jul 21.

    PubMed 20659956

  • Cuker A, Coles AJ, Sullivan H, Fox E, Goldberg M, Oyuela P, Purvis A, Beardsley DS, Margolin DH. A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Blood. 2011 Dec 8;118(24):6299-305. doi: 10.1182/blood-2011-08-371138. Epub 2011 Sep 29.

    PubMed 21960587

  • Riera R, Torloni MR, Martimbianco ALC, Pacheco RL. Alemtuzumab for multiple sclerosis. Cochrane Database Syst Rev. 2023 Jun 5;6(6):CD011203. doi: 10.1002/14651858.CD011203.pub3.

    PubMed 37272540

  • Coles AJ, Jones JL, Vermersch P, Traboulsee A, Bass AD, Boster A, Chan A, Comi G, Fernandez O, Giovannoni G, Kubala Havrdova E, LaGanke C, Montalban X, Oreja-Guevara C, Piehl F, Wiendl H, Ziemssen T. Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data. Mult Scler. 2022 Apr;28(5):842-846. doi: 10.1177/13524585211061335. Epub 2021 Dec 9.

    PubMed 34882037

  • Li Z, Richards S, Surks HK, Jacobs A, Panzara MA. Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis. Clin Exp Immunol. 2018 Dec;194(3):295-314. doi: 10.1111/cei.13208. Epub 2018 Oct 1.

    PubMed 30144037

  • Fox EJ, Wynn D, Coles AJ, Palmer J, Margolin DH; CAMMS223 Investigators. Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients. J Neurol Sci. 2016 Apr 15;363:188-94. doi: 10.1016/j.jns.2016.02.025. Epub 2016 Feb 12.

    PubMed 27000249

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Interferon beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg in people with Multiple Sclerosis, Relapsing-Remitting, run by Genzyme, a Sanofi Company at 49 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Poland, Russia, Croatia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Probability of Participants With Sustained Accumulation of Disability (SAD) (time frame: Up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00050778, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2015.

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