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

Sponsor

PDL BioPharma, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00109161

Collaborator

(none)

270

Enrollment

Locations

Duration (Months)

7.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Daclizumab (Anti-CD25 Humanized Monoclonal Antibody)	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2005

Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

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

Pharmacokinetics []
Immunogenicity []
Clinical improvement []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

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