Study of Subcutaneous Daclizumab in Patients With Active, Relapsing Forms of Multiple Sclerosis

A Phase II Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study of Subcutaneous Daclizumab in Patients With Active, Relapsing Forms of Multiple Sclerosis

This research study is being conducted in the U.S. and Europe to evaluate the safety and efficacy of daclizumab for the treatment of multiple sclerosis (MS).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Daclizumab (Anti-CD25 Humanized Monoclonal Antibody)

Detailed Description

PDL BioPharma, Inc. was formerly known as Protein Design Labs, Inc.

• Study Type: Interventional
• Enrollment: 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre-MS Research Program
    • Edmonton, Alberta, Canada, T6G-2C8
      • University of Alberta
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Center
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
  • Quebec
    • Gatineau, Quebec, Canada, PQ J8Y 1W7
      • Clinique SEP/NM
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
    • Scottsdale, Arizona, United States, 85013
      • Mayo Clinic
  • California
    • Berkeley, California, United States, 94705
      • Sutter East Bay Medical Foundation
  • Florida
    • Maitland, Florida, United States, 32751
      • Neurology Associates, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • The Multiple Sclerosis Center of Atlanta
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • KUMC Neurology
  • Louisiana
    • Shreveport,, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Maryland Center for MS
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University MS Center
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Grand Rapids, Michigan, United States, 49525
      • Michigan Medical P.C. Neurology
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • MS Center at Dartmouth
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Gimble MS Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Albany, New York, United States, 12205
      • Upstate Clinical Research
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10003
      • Hospital for Joint Diseases, MS Care Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • MS Center/CMC Meyers Park
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75214
      • The MS Center at Texas Neurology
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah CAMT
  • Washington
    • Seattle, Washington, United States, 98101
      • MS Hub Medical Group
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic, PS
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female age 18 to 55 years, inclusive.
• Diagnosis of MS by McDonald criteria.
• EDSS <7.0.
• On stable IFN-beta regimen for at least 6 months.
• The occurrence of either of the following within 9 months prior to screening: ≥1 MS relapse OR A qualifying MRI, defined as an MRI that showed at least one confirmed Gd-CEL of the brain or spinal cord, was performed independently of the study while the patient was on a stable IFN-beta regimen, and is deemed acceptable by the central reader.
• For females, women of non-childbearing potential or women of childbearing potential who provide a negative serum pregnancy test at screen and within 24 hours of first dose of study drug, and who agree to use effective contraception during the Treatment and Follow-up periods of the study.
• Willing and able to comply with the protocol, provision of informed consent in accordance with institutional and regulatory guidelines, and, for US sites only, authorization to use protected health information.

Exclusion Criteria:

• Pregnant or breast-feeding woman.
• Non-ambulatory patient.
• Clinically significant abnormality on screening ECG.
• Malignancy within the past 5 years, except for adequately treated non-melanoma skin carcinoma or in situ carcinoma of the cervix.
• History of HIV infection, positive serology for HBV (hepatitis B virus) or HCV (hepatitis C virus).
• Varicella (VZV) or herpes zoster virus infection, or any severe viral infection, within 6 weeks before screening or exposure to VZV within 21 days of screening.
• Abnormal hematology, as defined by the following laboratory values: *Hemoglobin ≤8.5 g/dL, *Lymphocytes ≤1.0 x 10^9/L, *Platelets ≤100 x 10^9/L, *Neutrophils ≤1.5 x 10^9/L.
• Significant organ dysfunction, including but not limited to cardiac, renal, liver, non-MS related CNS, pulmonary, vascular, gastrointestinal, endocrine, or metabolic dysfunction, or other disease or condition, which in the opinion of the PI (principal investigator) would make the patient an unsuitable candidate for the study. Guidelines for levels of unacceptable dysfunction include: *creatinine ≥1.6 mg/dL; *AST and ALT ≥2.5 times upper limit of normal (ULN); *alkaline phosphatase ≥2.5 times ULN; *history of myocardial infarction, congestive heart failure, or arrhythmias within 6 months prior to randomization.
• Use of any of the following: *Any of the following types of live virus vaccine from 4 weeks before randomization: measles/mumps/rubella vaccine, varicella zoster virus vaccine, oral polio vaccine, and nasal influenza vaccine. Use of these vaccines, however, by household contacts does not affect the eligibility of patients to enroll or continue in the study; *Systemic corticosteroids, adrenocorticotropic hormone, or plasma exchange within 4 weeks before the baseline MRI scan (no more than 72 hours before Day 0); *Azathioprine, mycophenolate mofetil, methotrexate, glatiramer acetate, or intravenous immune globulin within 6 months before randomization; *An immunomodulatory agent within 6 months before randomization, except for interferon-beta products required per protocol; *An investigational agent within 6 months before randomization unless this agent is non-immunomodulatory and the medical monitor or steering committee rules that its use is acceptable on the theoretical basis of a lapse of at least 5 serum half-lives since administration of the last possible dose; *A monoclonal antibody (eg, Rituxan®/ Rituximab) within 6 months before randomization; *Daclizumab at any time prior to randomization; *Cladribine, mitoxantrone, cyclophosphamide, CamPath® (alemtuzumab), natalizumab (TYSABRI®/Antegren) or other drugs targeting alpha 4 integrin, total lymphoid irradiation, or bone marrow transplant at any time
• Patients for whom MRI is contraindicated, ie, have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed.
• Primary progressive MS.
• Clinically unstable for 30 days before randomization (Patients who experienced a relapse, with or without steroid treatment, during the screening period may be re-screened after 30 days.)
• Elective surgery performed from 2 weeks prior to randomization or scheduled through Week 44
• Infection (viral, fungal, bacterial) requiring hospitalization or IV antibiotics within 8 weeks before randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Number of new or enlarged gadolinium contrast enhancing lesions (Gd-CELs) on monthly brain MRIs collected between Weeks 8 to 24 in daclizumab- vs. placebo-treated patients

Secondary Outcome Measures

Outcome Measure
Pharmacokinetics
Clinical improvement
Immunogenicity

Collaborators and Investigators

• Sponsor: PDL BioPharma, Inc.
• Investigators: Principal Investigator: Richard Dickson, M.D., Wenatchee Valley Medical Center; Principal Investigator: Steven Pugh, M.D., Rockwood Clinic, PS; Principal Investigator: Daniel Wynn, M.D., Consultants in Neurology; Principal Investigator: Theodore J. Phillips, M.D., The MS Center at Texas Neurology; Principal Investigator: Joanna Cooper, Sutter East Bay Medical Foundation; Principal Investigator: James R. Storey, Upstate Clinical Research; Principal Investigator: Malcolm Gottesman, M.D., Winthrop University Hospital; Principal Investigator: Herman Sullivan, M.D., Michigan Medical P.C. Neurology; Principal Investigator: Timothy Vollmer, M.D., St. Joseph's Hospital and Medical Center, Phoenix; Principal Investigator: Jeffery Dunn, M.D., MS Hub Medical Group; Principal Investigator: S. Mitchell Freedman, M.D., Raleigh Neurology Associates; Principal Investigator: Joseph Herbert, M.D., Hospital for Joint Diseases, MS Care Center; Principal Investigator: Omar Khan, M.D., Wayne State University MS Center; Principal Investigator: Marcelo Kremenchutzky, M.D., London Health Sciences Centre; Principal Investigator: Sharon Lynch, M.D., CLMC Neurology; Principal Investigator: Alireza Minagar, M.D., Louisiana State University Health Sciences Center; Principal Investigator: Jeffrey English, M.D., The Multiple Sclerosis Center of Atlanta; Principal Investigator: Andrew Goodman, M.D., University of Rochester; Principal Investigator: Michael Kaufman, M.D., MS Center/CMC; Principal Investigator: Florian P. Thomas, M.D., St. Louis University Hospital; Principal Investigator: Clyde Markowitz, M.D., University of Pennsylvania; Principal Investigator: Jayne Martin, M.D., Michigan State University; Principal Investigator: Maria Melanson, M.D., Health Sciences Center; Principal Investigator: MaryAnn Picone, M.D., Gimble MS Center; Principal Investigator: Christopher Bever, M.D, Maryland Center for MS; Principal Investigator: Gregg G. Blevins, M.D., University of Alberta; Principal Investigator: Kasper Lloyd, M.D., MS Center at Dartmouth; Principal Investigator: Yves Lapierrre, M.D., Montreal Neurological Institute; Principal Investigator: John W. Rose, M.D., University of Utah CAMT; Principal Investigator: Michael Yeung, M.D., Foothills Medical Centre; Principal Investigator: Neil Lava, M.D., Albany Medical College; Principal Investigator: Jonathan L. Carter, M.D., Mayo Clinic; Principal Investigator: Francois Jacques, M.D., Clinique SEP/NM; Principal Investigator: William Honeycutt, M.D., Neurology Associates, P.A.; Principal Investigator: Istvan Pirko, M.D., University of Cincinnati; Principal Investigator: Ed Fox, M.D., Central Texas Neurology

Publications and helpful links

General Publications

• Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, Fong A, Rose JW; CHOICE investigators. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol. 2010 Apr;9(4):381-90. doi: 10.1016/S1474-4422(10)70033-8. Epub 2010 Feb 15. Erratum In: Lancet Neurol. 2010 Aug;9(8):759. Wadinger, K [corrected to Wandinger, K].

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Study Completion: October 1, 2006

Study Registration Dates

• First Submitted: April 22, 2005
• First Submitted That Met QC Criteria: April 22, 2005
• First Posted (ESTIMATE): April 25, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): August 5, 2008
• Last Update Submitted That Met QC Criteria: August 2, 2008
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Keywords: Multiple Sclerosis, MS, CNS, Daclizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Antibodies; Antibodies, Monoclonal; Daclizumab
• Other Study ID Numbers: DAC-1012