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

NCT00050778 | Completed Phase 2 Results DMC

• 1 other identifier: CAMMS223
• Study Type: interventional
• Target: 334
• Locations: 5 countries
• Sites: 49

Brief 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 therapies other than steroids. The study was conducted for an initial period of 3 years and a follow-up to 5 years or more.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple Sclerosis; Active Relapsing-Remitting Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 3 years

• 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.

  Up to 3 years

Secondary Outcomes (3)

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

  Year 3

• Percent Change From Baseline in T1 Cerebral Volume at Year 3

  Baseline, Year 3

• Percent Change From Baseline in MRI T2 Lesion Volume at Year 3

  Baseline, Year 3

Study Arms (3)

Interferon Beta-1a

ACTIVE COMPARATOR

Biological: Interferon beta-1a

Alemtuzumab 12 mg

EXPERIMENTAL

Biological: Alemtuzumab 12 mg

Alemtuzumab 24 mg

EXPERIMENTAL

Biological: Alemtuzumab 24 mg

Interventions

Interferon beta-1a BIOLOGICAL

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

Also known as: Rebif®

Interferon Beta-1a

Alemtuzumab 12 mg BIOLOGICAL

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).

Also known as: Lemtrada

Alemtuzumab 12 mg

Alemtuzumab 24 mg BIOLOGICAL

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).

Also known as: Lemtrada

Alemtuzumab 24 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead
• Bayer: collaborator

Study Sites (49)

Mayo Clinic Scottsdale Arizona

Scottsdale, Arizona, 85259, United States

Location

Clinical Trials, Inc

Little Rock, Arkansas, 72205, United States

Location

East Bay Physicians Medical Group

Berkeley, California, 94705, United States

Location

Nerve Pro Research

Irvine, California, 92618, United States

Location

Neuro-Therapeutics, Inc.

Pasadena, California, 91105, United States

Location

Neurological Research Institute of the East Bay

Walnut Creek, California, 938-1343, United States

Location

Neurologic Research Institute/Mile High Research Center

Denver, Colorado, 80218, United States

Location

Neurological Service of Orlando

Orlando, Florida, 32806, United States

Location

Neurological Associates/ Research Dept.

Pompano Beach, Florida, 33060, United States

Location

Neurology Clinical Research, Inc.

Sunrise, Florida, 3335-6637, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Medical Research and Health Education

Columbus, Georgia, 31909, United States

Location

Consultants in Neurology, Ltd

Northbrook, Illinois, 60062, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46805, United States

Location

Associate in Neurology

Lexington, Kentucky, 40503, United States

Location

University of Maryland -Maryland Center for MS

Baltimore, Maryland, 21201, United States

Location

Wayne State University Department of Neurology

Detroit, Michigan, 48201, United States

Location

Michigan Institute for Neurological Disorders

Farmington Hills, Michigan, 48334, United States

Location

Michigan Medical P.C. Neurology

Grand Rapids, Michigan, 49525, United States

Location

Mayo Clinic Rochester Department of Neurology

Rochester, Minnesota, 55905, United States

Location

Nevada Neurological Consultants, Ltd.

Las Vegas, Nevada, 89102, United States

Location

University Hospital an Medical Center

Stony Brook, New York, 11794, United States

Location

ALL-Trials Clinical Research, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Neurological Associates of Tulsa, Inc

Tulsa, Oklahoma, 74137, United States

Location

Neurosciencies and Pain Research

Allentown, Pennsylvania, 18103-6296, United States

Location

Neurology, PC

Knoxville, Tennessee, 37934, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

Dallas Neurological Associate

Richardson, Texas, 75080, United States

Location

Central Texas Neurology Consultants PA

Round Rock, Texas, 78681, United States

Location

Integra Clinical Research, LLC

San Antonio, Texas, 78231, United States

Location

Neurology Center of San Antonio

San Antonio, Texas, 78258, United States

Location

Department of Neurology, University Hospital "Osijek"

Osijek, Croatia

Location

Department of Neurology, Clinical Hospital Centre "Rijeka"

Rijeka, Croatia

Location

Department of Neurology, Clinical Hospital Centre "Zagreb"

Zagreb, Croatia

Location

Department of Neurology, General Hospital "Sveti Duh"

Zagreb, Croatia

Location

Department of Neurology, University Hopsital "Sestre Milosrdnice"

Zagreb, Croatia

Location

Centrum Neurologii Klinicznej

Krakow, Poland

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej

Lodz, Poland

Location

Klinika Neurologii

Lublin, Poland

Location

Oddzial Kliniczny Neurologii

Poznan, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, Poland

Location

Katedra i Klinika Neurologii

Warsaw, Poland

Location

Russian State Medical University

Moscow, 117437, Russia

Location

Neurology Scientific Center RAMS

Moscow, 125367, Russia

Location

Moscow City Hospital #11

Moscow, Russia

Location

Moscow City Hospital #61

Moscow, Russia

Location

Institute of Human brain RAS

Saint Petersburg, 197376, Russia

Location

St. Petersburg State Pavlov Medical University

Saint Petersburg, Russia

Location

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Location

Related Publications (12)

• 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.

  PMID: 16044212 BACKGROUND

• 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.

  PMID: 18946064 RESULT

• 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.

  PMID: 24170099 RESULT

• 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.

  PMID: 23459567 RESULT

• 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.

  PMID: 22442431 RESULT

• 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.

  PMID: 21397567 RESULT

• 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.

  PMID: 20659956 RESULT

• 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.

  PMID: 21960587 RESULT

• 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.

  PMID: 37272540 DERIVED

• 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.

  PMID: 34882037 DERIVED

• 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.

  PMID: 30144037 DERIVED

• 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.

  PMID: 27000249 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Interferon beta-1a; Alemtuzumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-us@sanofi.com

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2002
• First Posted: December 23, 2002
• Study Start: December 1, 2002
• Primary Completion: September 1, 2007
• Study Completion: January 1, 2010
• Last Updated: January 8, 2015
• Results First Posted: August 25, 2009

Record last verified: 2015-01

Locations

US (31); PL (6); CR (5); RU (6); GB (1)