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

• ClinicalTrials.gov Identifier: NCT00109161
• Recruitment Status: Completed
• First Posted: April 25, 2005
• Last Update Posted: August 5, 2008
• Sponsor: PDL BioPharma, Inc.
• Information provided by: Facet Biotech

Tracking Information

• First Submitted Date: April 22, 2005
• First Posted Date: April 25, 2005
• Last Update Posted Date: August 5, 2008
• Study Start Date: April 2005
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: June 23, 2005): 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
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2005)

• Pharmacokinetics
• Immunogenicity
• Clinical improvement

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Subcutaneous Daclizumab in Patients With Active, Relapsing Forms of Multiple Sclerosis
• Official Title: A Phase II Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study of Subcutaneous Daclizumab in Patients With Active, Relapsing Forms of Multiple Sclerosis
• Brief Summary: 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).
• Detailed Description: PDL BioPharma, Inc. was formerly known as Protein Design Labs, Inc.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Multiple Sclerosis
• Intervention: Drug: Daclizumab (Anti-CD25 Humanized Monoclonal Antibody)
• Study Arms: Not Provided
• 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].

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: June 23, 2005): 270
• Original Enrollment: Same as current
• Study Completion Date: October 2006
• Primary Completion Date: Not Provided

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00109161
• Other Study ID Numbers: DAC-1012
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: PDL BioPharma, Inc.
• Original Study Sponsor: Facet Biotech
• Collaborators: Not Provided

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

• PRS Account: Facet Biotech
• Verification Date: August 2008