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

• Conditions: This study is performed in patients with relapsing forms of Multiple Sclerosis. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), thought to be mediated by autoreactive T cells. Daclizumab is a genetically engineered humanized IgG1 monoclonal antibody that binds specifically to CD25 (alpha chain of the IL-2 receptor) and achieves immunosuppression at least in part by competitive antagonism of IL-2-induced T cell proliferation.

• Registration Number: EUCTR2005-001567-55-AT
• Lead Sponsor: Protein Design Labs, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-23
• Last Update Posted: 13 May 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

1.Males and females, 18 to 65 years of age, inclusive.
2.Diagnosis of MS by the McDonald criteria.
3.Score <7.0 on the EDSS.
4.On stable IFN-beta regimen, defined as at least 6 months on the same dose of the same drug product. Dose titration is allowed during the initial 2 months of IFN-beta treatment as long as the patient has remained on the adjusted dose for the remainder of the 6 month period. Patients who wish to participate must agree to remain on their same IFN beta regimen until Week 44 of the study.
5.The occurrence of either of the following within 9 months prior to screening:
oAt least one MS relapse (as defined in section 2.2.2, Secondary Endpoints, Item No. 3) while the patient was on a stable IFN-beta regimen or
oA qualifying MRI, defined as an MRI that showed at least one confirmed gadolinium contrast-enhancing lesion (Gd-CEL) of the brain or spinal cord, was performed while the patient was on a stable IFN-beta regimen, and is deemed acceptable by the central reader. (An MRI that is used to qualify a patient is obtained independently of the study. The central reader will qualify scans [submitted as either digital or film copies] within 72 hours of receiving the scan at the central read center.)
6.For females, those who meet either of the following criteria:
oNon-childbearing potential, as documented by 1) surgical sterility from oophorectomy and/or hysterectomy or 2) a medical history (clinically or by follicle-stimulating-hormone testing) of being postmenopausal for at least the past 2 years. A history of tubal ligation, evidence of a spouse or sexual partner being sterile, or a history of sexual abstinence is insufficient evidence of non-childbearing potential.
oChildbearing potential, provide a negative serum pregnancy test at screening and within 24 hours of administration of first dose of study drug, and agree to utilize effective contraception or remain abstinent during the entire treatment and follow-up periods of the study.
7.Willing and able to comply with the protocol, provide informed consent in accordance with institutional and regulatory guidelines, and, for patients at US sites, authorization to use protected health information (HIPAA).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Pregnant or breast-feeding female
2.Non-ambulatory patient
3.Clinically significant abnormality on a screening electrocardiogram (ECG)
4.Malignancy within the past 5 years except for adequately treated non-melanoma skin carcinoma or in situ carcinoma of the cervix
5.A medical history of infection with the human immunodeficiency virus (HIV)
6.Positive serology for infection with hepatitis B or C virus (HBV or HCV)
7.Varicella or herpes zoster virus infection or any severe virus infection within 6 weeks before screening
8.Exposure to varicella zoster virus within 21 days before screening
9.Abnormal hematology, defined as any of the following:
•Hemoglobin <= 8.5 g/dL
•Lymphocytes <=1.0 x 109/L
•Platelets <=100 x 109/L
•Neutrophils <=1.5 x 109/L
10.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 principal investigator (PI) 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 x upper limit of normal [ULN]; alkaline phosphatase >=2.5 x ULN; history of myocardial infarction, congestive heart failure, or arrhythmias within 6 months prior to randomization.
11.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
12.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
13.Primary progressive MS
14.Clinically unstable for 30 days before randomization (Patients who experience a relapse, with or without steroid treatment, during the screening period may be re-screened after 30 days.)
15.Elective surgery performed from 2 weeks prior to randomization or scheduled through Week 44
16.Infection (viral, fungal, bacterial) requiring hospitalization or IV antibiotics within 8 weeks before randomization

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of Study DAC-1012 is to evaluate the efficacy of daclizumab in patients who have active, relapsing forms of MS and are currently on IFN-beta therapy.;Secondary Objective: The secondary objectives are, in this study population of patients with active, relapsing forms of MS, to: <br>1)Determine the safety profile of daclizumab<br>2)Evaluate pharmacologic parameters (ie, pharmacokinetics and pharmacodynamics)<br>3)Evaluate immunogenicity (ie, development of antibodies to daclizumab [anti-DAC])<br>;Primary end point(s): The primary efficacy endpoint is the 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.