Clinical trial NCT00109161: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis, MS, CNS, Daclizumab
Lead sponsor: Facet Biotech
Sponsor class: INDUSTRY
First posted: 2005-04-25
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
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 outcomes:
measure: Pharmacokinetics
measure: Immunogenicity
measure: Clinical improvement
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Berkeley
country: United States
facility: Sutter East Bay Medical Foundation
state: California
city: Maitland
country: United States
facility: Neurology Associates, P.A.
state: Florida
city: Atlanta
country: United States
facility: The Multiple Sclerosis Center of Atlanta
state: Georgia
city: Northbrook
country: United States
facility: Consultants in Neurology
state: Illinois
city: Kansas City
country: United States
facility: KUMC Neurology
state: Kansas
city: Shreveport,
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Maryland Center for MS
state: Maryland
city: Detroit
country: United States
facility: Wayne State University MS Center
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Grand Rapids
country: United States
facility: Michigan Medical P.C. Neurology
state: Michigan
city: St. Louis
country: United States
facility: St. Louis University Hospital
state: Missouri
city: Lebanon
country: United States
facility: MS Center at Dartmouth
state: New Hampshire
city: Teaneck
country: United States
facility: Gimble MS Center
state: New Jersey
city: Albany
country: United States
facility: Upstate Clinical Research
state: New York
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Hospital for Joint Diseases, MS Care Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: MS Center/CMC Meyers Park
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: The MS Center at Texas Neurology
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah CAMT
state: Utah
city: Seattle
country: United States
facility: MS Hub Medical Group
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic, PS
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Calgary
country: Canada
facility: Foothills Medical Centre-MS Research Program
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: Health Sciences Center
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Gatineau
country: Canada
facility: Clinique SEP/NM
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute
state: Quebec
Study officials:
affiliation: Wenatchee Valley Medical Center
name: Richard Dickson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rockwood Clinic, PS
name: Steven Pugh, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Consultants in Neurology
name: Daniel Wynn, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The MS Center at Texas Neurology
name: Theodore J. Phillips, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sutter East Bay Medical Foundation
name: Joanna Cooper
role: PRINCIPAL_INVESTIGATOR
affiliation: Upstate Clinical Research
name: James R. Storey
role: PRINCIPAL_INVESTIGATOR
affiliation: Winthrop University Hospital
name: Malcolm Gottesman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan Medical P.C. Neurology
name: Herman Sullivan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Joseph's Hospital and Medical Center, Phoenix
name: Timothy Vollmer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: MS Hub Medical Group
name: Jeffery Dunn, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Raleigh Neurology Associates
name: S. Mitchell Freedman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital for Joint Diseases, MS Care Center
name: Joseph Herbert, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University MS Center
name: Omar Khan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Centre
name: Marcelo Kremenchutzky, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CLMC Neurology
name: Sharon Lynch, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Louisiana State University Health Sciences Center
name: Alireza Minagar, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Multiple Sclerosis Center of Atlanta
name: Jeffrey English, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Andrew Goodman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: MS Center/CMC
name: Michael Kaufman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Louis University Hospital
name: Florian P. Thomas, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Clyde Markowitz, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan State University
name: Jayne Martin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Health Sciences Center
name: Maria Melanson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Gimble MS Center
name: MaryAnn Picone, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Maryland Center for MS
name: Christopher Bever, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Gregg G. Blevins, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: MS Center at Dartmouth
name: Kasper Lloyd, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Neurological Institute
name: Yves Lapierrre, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah CAMT
name: John W. Rose, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Foothills Medical Centre
name: Michael Yeung, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Albany Medical College
name: Neil Lava, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Jonathan L. Carter, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique SEP/NM
name: Francois Jacques, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology Associates, P.A.
name: William Honeycutt, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: Istvan Pirko, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Texas Neurology
name: Ed Fox, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.