Comparison of Daclizumab HYP and Avonex® in Multiple Sclerosis

Phase 1

Conditions: Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Relapsing-remitting Multiple Sclerosis
MedDRA version: 16.0Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders

Registration Number: EUCTR2009-012500-11-FI

Lead Sponsor: Biogen Idec Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1800

Inclusion Criteria

To be eligible for this study, candidates must meet the following eligibility criteria prior to randomization or at the timepoint specified in
the individual criteria listed below:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject
privacy regulations.
2. Must be 18 to 55 years of age, inclusive, at the time of consent.
3. Must have a confirmed diagnosis of RRMS according to McDonald criteria, numbers 1 through 4 (Polman et al, 2005), and a cranial MRI demonstrating lesion(s) consistent with MS (it is not necessary to obtain a current scan if a scan performed previously is available; if a previous scan is not available, then the baseline scan may be used).
4. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
5. Must meet one of the following disease activity-related criteria:
a) Two or more clinical relapses within the previous 3 years with at least 1 clinical relapse in the 12 months prior to randomization.
OR
b) One or more clinical relapses and 1 or more new MRI lesions (Gd+ and/or T2 hyperintense lesion) within the previous 2 years with at least one of these events in the 12 months prior to randomization. The new MRI lesion must be distinct from one associated with the clinical relapse. The baseline MRI may be used to satisfy this criterion.
Note: For inclusion purposes, a clinical relapse is defined as neurologic signs and/or symptoms documented in the medical record of at least 24 hours duration that are determined by the Investigator or the Treating
Neurologist as consistent with an MS relapse. Time since relapse should be measured from the time of relapse onset. When inclusion is based on a new MRI lesion, activity must be verified by the central MRI reading center.
6. Women of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue
contraception for 4 months after their last dose of study treatment.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1800
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Diagnosis of primary progressive, secondary progressive, or
progressive relapsing MS (as defined by Lublin and Reingold, 1996).
2.Known intolerance, contraindication to, or history of non compliance
with Avonex 30 mcg.3.History of malignancy; however, subjects with a
history of excised or treated basal cell carcinoma or fewer than 3
squamous cell carcinomas are eligible to participate in this
study.4.History of severe allergic or anaphylactic reactions.
5.Known hypersensitivity to study drugs or their excipients.6.History of
abnormal laboratory results that are indicative of any significant cardiac,
endocrine, hematological, hepatic, immunologic, metabolic, urologic,
pulmonary, gastrointestinal, dermatologic, psychiatric, renal,
neurological (other than MS), and/or other major disease that would
preclude administration of DAC HYP or Avonex.7.History of human
immunodeficiency virus (HIV) or other immunodeficient conditions.
8.History of drug or alcohol abuse within the 2 years prior to
randomization.9.History of seizure disorder or unexplained blackouts OR
history of a seizure within 6 months prior to Baseline. 10.History of
suicidal ideation or an episode of clinically severe depression within 3
months prior to Day 1. Subjects receiving ongoing antidepressant
therapy will not be excluded from the study unless the medication has
been increased within the 6 months prior to Baseline.11.An MS relapse
that has occurred within the 50 days prior to randomization AND/OR the
subject has not stabilized from a previous relapse prior to
randomization.12.Known history of, or positive screening test result for
hepatitis C virus or hepatitis B virus. 13.Varicella or herpes zoster virus
infection or any severe viral infection within 6 weeks before
screening.14.Exposure to varicella zoster virus within 21 days before
screening.15.Any of the following abnormal blood tests at screening:
• hemoglobin =9.0 g/dL
• platelets =100 x 10^9/L
• lymphocytes =1.0 x 10^9/L
• neutrophils =1.5 x 10^9/L
• alanine aminotransferase/serum glutamate pyruvate transaminase
(ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic
transaminase (AST/SGOT), or gamma glutamyl-transferase =2 times the
upper limit of normal (ULN)
• serum creatinine =ULN
16.Any previous treatment with daclizumab or other anti-CD25
monoclonal antibody.17.Any type of live virus vaccine from 4 weeks
before randomization.18.Infection requiring hospitalization or
intravenous (IV) antibiotics within 8 weeks before
randomization.19.Elective surgery performed from 2 weeks prior to
randomization or scheduled through end of the study.
20.Treatment with another investigational drug or approved therapy for
investigational use within the 6 months prior to randomization.21.Prior
treatment with the any of the following:
• total lymphoid irradiation• cladribine• T cell or T cell receptor
vaccination• any therapeutic monoclonal antibody, except natalizumab
22.Prior treatment with mitoxantrone, cyclophosphamide, fingolimod, or
natalizumab within 1 year prior to randomization.23.Prior treatment
with any of the following within the 6 months prior to randomization:
• cyclosporine• azathioprine• methotrexate• mycophenolate mofetil•
intravenous immunoglobulin • plasmapheresis or
cytapheresis.24.Treatment with any of the following medications within
the 30 days prior to randomization:• IV corticosteroid treatment• oral
corticosteroid treatment• glatiramer acetate
25.Initiation of treatment or dose adjustment of

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): • Annualized relapse rate (ARR);Timepoint(s) of evaluation of this end point: Any relapses and time on study that occur up to Week 144;Main Objective: The primary study objective is to test the superiority of DAC HYP compared to IFN ß-1a in preventing MS relapse in subjects with relapsing remitting MS (RRMS).;Secondary Objective: The secondary study objectives are to test the superiority of DAC HYP compared to IFN ß-1a in slowing functional decline and disability<br>progression and maintaining quality of life in this subject population.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): a) Number of new or newly-enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) over 96 weeks<br>b) Proportion of subjects with sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from baseline EDSS =1.0 that is sustained for 12 weeks or at least a 1.5-point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks<br>c) Proportion of subjects who are relapse-free <br>d) Proportion of subjects with a =7.5 point worsening from baseline the MSIS-29 physical score at 96 weeks;Timepoint(s) of evaluation of this end point: a) Weeks 0, 24, 96, (and also 144/early termination)<br>b) Screening, weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144/early termination (and also follow up visits 1 and 2, and unscheduled relapse assessment<br>c) up to week 144 (end of study visit)<br>d) 96 weeks