Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis
|First Received Date ICMJE||October 31, 2003|
|Last Updated Date||August 17, 2011|
|Start Date ICMJE||October 2003|
|Primary Completion Date||October 2007 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Reduction in mean number of new gaolinium-enhancing lesions in the treatment phase (Weeks 18 to 30) versus baseline (Weeks -12 to 0). [ Designated as safety issue: Yes ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00071838 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Mean change in the MS functional composite from completion of treatment. Reduction of mean number of new gaolinium-enhancing lesions at the completion of treatment. Mean change in Multiple Sclerosis Quality of Life Inventory from completion of t...|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis|
|Official Title ICMJE||Zenapax (Daclizumab) Admin to Pts With Multiple Sclerosis (ZAP MS): Effect of Intravenously Admin Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (Daclizumab) on Inflammatory Activity in the Central Nervous System|
This study will examine the safety of Zenapax (daclizumab) in patients with multiple sclerosis (MS). MS is thought to be caused by an over-reactive immune response. T-lymphocytes (cells of the immune system), are thought to damage myelin, a substance that covers the nerve and parts of the spinal cord and is damaged in patients with MS. Interleukin-2 is a natural substance in the body that is necessary for the growth of T-lymphocytes. Zenapax is a genetically engineered antibody that blocks the activity of interleukin-2 and thus interferes with the growth of lymphocytes. Therefore, Zenapax may prevent some of the damage to myelin that occurs in multiple sclerosis.
Patients between 18 and 65 years of age with relapsing remitting MS may be eligible for this study. Patients with secondary-progressive or primary progressive MS may not participate. Candidates will be screened with a complete neurological and medical evaluation and review of medical records.
Participants will undergo the following tests and procedures:
Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease leading to central nervous system (CNS) inflammation, demyelination, axonal loss, and leads to substantial disability in young adults. Existing approved treatments include interferon beta, glatiramer acetate and mitoxantrone. These therapies are only moderately effective in reducing disease activity.
The Neuroimmunology Branch (NIB) has during the last three years tested the tolerability and safety of monthly intravenously administered daclizumab (Zenapax(Registered Trademark)), a humanized monoclonal antibody against the IL-2 receptor alpha chain, in patients who receive interferon-beta, but responded incompletely to therapy with interferon-beta. Daclizumab has been well tolerated and inhibited inflammatory disease activity by almost 90%. Under an amendment of this protocol, it was demonstrated that the efficacy of daclizumab is maintained once interferon-beta therapy is discontinued.
In the current trial, we will test the efficacy of daclizumab alone in relapsing-remitting MS patients. This trial is a single-centre, open-label, baseline to treatment cross-over phase II trial. Daclizumab will be administered intravenously at 1mg/kg bodyweight. Contrast-enhancing MRI lesions will serve as the primary outcome measure in this phase II trial, and a number of clinical, MRI, and immunological parameters will be measured as secondary and tertiary outcomes. Daclizumab is a promising new immunomodulatory treatment for relapsing-remitting MS.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||Multiple Sclerosis, Relapsing-Remitting|
|Intervention ICMJE||Drug: Daclizumab
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2011|
|Primary Completion Date||October 2007 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
To be eligible for entry into the study, patients must meet the following criteria at the time of enrollment. Re-assessment of the inclusion criteria will occur on day zero of the twelve-month treatment phase.
Between the ages of 18 and 65 years, inclusive.
Patients with relapsing-remitting MS according to published criteria.
EDSS score between 1.0 and 5.5.
Patients have either failed standard therapies (interferon-beta, glatiramer acetate) by clinical measures, or are not eligible for standard therapies, or opted not to start or continue with any of the standard therapies.
Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.
Age criteria for inclusion in this study follow those of published diagnostic criteria for multiple sclerosis. Due to the uncommon occurrence of MS in individuals under the age of 18 and the requirement to study a large MS cohort to include these rarely occurring patients, this is an appropriate lower age range.
Patient decision not to start, or not to continue with standard immunomodulatory therapy, has to be made by the patient after discussing conventional treatment options to ensure the patient has made an informed decision. Additionally, the consent document provided to the patient will explicitly state the currently approved therapies and their potential benefits.
ELIGIBILITY CRITERIA FOR INITIATING THERAPY:
To be eligible to proceed to the treatment phase of the study, patients must have at least two new gadolinium-enhancing lesions or greater in the four sequential baseline MRI scans (average of greater than or equal to 0.5 gadolinium-enhancing lesions or more).
Patients can not have a relapse during 30 days before initiation of treatment. If a relapse occurs during this period and eligibility criteria are otherwise fulfilled, treatment (day one) will be delayed while corticosteroids are administered. If corticosteroids are administered, the MRI during that period will not be considered. An additional MRI will be added at 4 weeks following the completion of corticosteroids, to maintain a total of four MRI's that are analyzed in the baseline period. In the event of relapse, the baseline period will be prolonged, as necessary, to meet these criteria.
EXCLUSION CRITERIA FOR PRE-TREATMENT SCREENING:
Patients will be excluded from the study if any of the exclusion criteria exist at the time of enrollment. Re-assessment of the exclusion criteria will occur on day zero of the twelve month treatment phase.
Diagnosis of secondary-progressive or primary-progressive MS, as defined by published diagnostic criteria.
Abnormal screening/baseline blood tests exceeding any of the limits defined below:
Pregnant or breast-feeding female.
History or signs of immunodeficiency.
Concurrent clinically significant (as determined by the investigators) cardiac, immunological, pulmonary, neurological, renal or other major disease.
Any contraindication to monoclonal antibody therapy. Contraindication to monoclonal antibody therapy includes prior history of serum-sickness or similar hypersensitivity reaction to receipt of monoclonal antibody or intravenous immunoglobulin therapies.
Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.
If prior treatments were administered, the patient must be off the following treatment agents for the required period prior to enrollment:
Prior treatment with other investigational drugs or procedures will be evaluated individually by the investigators.
History of alcohol or drug abuse within the 5 years prior to enrollment.
Female patients who are not post-menopausal or surgically sterile who are not using an acceptable method of contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Documentation that the patient is post-menopausal or surgically sterile must be available prior to enrollment.
Male patients who are not surgically sterile and not practicing adequate contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Documentation that the patient is surgically sterile must be available prior to enrollment.
Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient returning for follow-up visits on schedule.
Previous participation in this study.
|Ages||18 Years to 65 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00071838|
|Other Study ID Numbers ICMJE||040019, 04-N-0019|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Bibiana Bielekova, M.D./National Institute of Neurological Disorders and Stroke, National Institutes of Health|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||August 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP