Advanced MRI Measures of Repair in Alemtuzumab Treated Patients

NCT01307332 | Completed Phase 3 DMC

• 2 other identifiers: H10-02482142402
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

There are two parts to this investigator sponsored trial (IST):

1. 1.To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
2. 2.To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis; MS; Relapsing Remitting Multiple Sclerosis; RRMS; Alemtuzumab; Demyelination; Remyelination; Tolerogenic; T cells; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Outcome Measures

Primary Outcomes (1)

• Changes in normal appearing white matter from baseline through month 24.

  The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.

  24 months

Secondary Outcomes (1)

• To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis from baseline through month 48.

  48 months

Study Arms (1)

MabCampath-1h

EXPERIMENTAL

Single arm, single cohort study, all subjects will be dosed with alemtuzumab.

Drug: MabCampath-1h

Interventions

MabCampath-1h DRUG

Drug:10 mg/mL alemtuzumab intravenous infusion. Form: Sterile, clear, colorless solution. Dosage: 2 cycles. Month 0 dosed over 5 consecutive days; month 12 dosed over 3 consecutive days.

Also known as: Alemtuzumab

MabCampath-1h

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
• Age 18 to 50 years old (inclusive)
• Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening
• Onset of MS symptoms within 15 years of screening
• Neurostatus (EDSS) score 0.0 to 5.0 (inclusive)
• MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with 1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician.

You may not qualify if:

• Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferon's, IV immunoglobulin, and glatiramer acetate
• Exposure to natalizumab within 6 months of screening
• Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment
• Has any progressive form of MS
• History of malignancy (exception for basal cell skin carcinoma)
• Previous hypersensitivity reaction to other immunoglobulin product
• Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
• CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count \<LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed
• Seropositivity for human immunodeficiency virus (HIV)
• Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis)
• Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies
• Active infection
• Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis.
• Infection with hepatitis B virus or hepatitis C virus
• Of childbearing potential with a positive serum pregnancy test

Sponsors & Collaborators

• University of British Columbia: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

University of British Columbia Hospital

Vancouver, British Columbia, V6T 2B5, Canada

Location

Related Publications (3)

• 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 BACKGROUND

• 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

• Gilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2020 Jun 15;17(1):189. doi: 10.1186/s12974-020-01847-9.

  PMID: 32539719 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis; Demyelinating Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Leukoencephalopathies; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Anthony Traboulsee, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: March 2, 2011
• Study Start: March 1, 2011
• Primary Completion: September 28, 2018
• Study Completion: September 28, 2018
• Last Updated: October 16, 2018

Record last verified: 2018-10

Locations

CA (1)