Advertisement

Topics

Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis

2014-08-27 03:54:47 | BioPortfolio

Summary

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:

- Baseline evaluation: Participants have four magnetic resonance imaging (MRI) scans over a 3-month period to assess disease activity. For the MRI scans, the patient lies on a table that slides into the scanner - a narrow metal cylinder with a strong magnetic field. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Only patients with activity at or above a certain level are eligible to continue with the treatment phase of the study.

- Zenapax treatment: Patients receive intravenous (through a vein) infusions of Zenapax. The first two infusions are 2 weeks apart, followed by 13 monthly infusions.

- MRI scans: Patients undergo MRI scanning before every infusion to evaluate disease activity and identify new brain lesions.

- Blood and urine tests: Blood and urine samples are collected at each clinic visit for routine laboratory evaluations, immunologic study, and genetic testing to determine a predisposition for responding to Zenapax treatment.

- Lumbar puncture (spinal tap): This procedure will be done during the last month before starting treatment and during the seventh month of treatment to examine immune changes that occur in the cerebrospinal fluid (CSF), which circulates through and surrounds the brain and spinal cord. A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle.

- Skin test: A needle is placed just under the skin is done to assess the patient's immune status to common antigens such as tetanus, mumps and candida.

- Lymphocytopheresis: Lymphocytes are collected three times - once during the last month of baseline before starting treatment, once during the fifth month of treatment, and once during the last month of treatment - for immunologic study. Blood is collected through a needle in an arm vein in a similar way to donating blood. The blood flows from the vein through a catheter (plastic tube) into a machine that separates it into its components by centrifugation (spinning). The lymphocytes are removed and the rest of the blood (red cells, plasma and platelets) is returned to the body, either through the same needle or through another needle in the other arm.

Description

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 Design

Primary Purpose: Treatment

Conditions

Multiple Sclerosis, Relapsing-Remitting

Intervention

Daclizumab

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Completed

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:54:47-0400

Clinical Trials [1459 Associated Clinical Trials listed on BioPortfolio]

Safety and Efficacy Study of Daclizumab HYP to Treat Relapsing-Remitting Multiple Sclerosis

The purpose of this study is to determine the effect of 2 different doses of daclizumab on reducing relapses in subjects with relapsing-remitting MS.

Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing Remitting Multiple Sclerosis

Extended DAC HYP monotherapy from study 205MS202 in order to evaluate long term safety and efficacy of DAC HYP in subjects with relapsing remitting multiple sclerosis (MS).

Safety and Efficacy Extension Study of Daclizumab HYP to Treat Relapsing-Remitting Multiple Sclerosis

Extend DAC HYP therapy from Study 205MS201 in order to evaluate long term safety and efficacy of DAC HYP in subjects with relapsing-remitting MS.

Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis

The primary study objective is to test the superiority of DAC HYP compared to IFN β-1a in preventing MS relapse in subjects with Relapsing Remitting Multiple Sclerosis. The secondary stu...

Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab

The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclero...

PubMed Articles [6161 Associated PubMed Articles listed on BioPortfolio]

Circulating lymphocyte levels and relationship with infection status in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta.

Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis.

Consistent efficacy of daclizumab beta across patient demographic and disease activity subgroups in patients with relapsing-remitting multiple sclerosis.

Daclizumab beta is a humanized monoclonal antibody specific for the human interleukin-2 receptor alpha chain (CD25). In two pivotal studies in relapsing multiple sclerosis (MS), patients treated with ...

A 8-year retrospective cohort study comparing Interferon-β formulations for relapsing-remitting multiple sclerosis.

Interferon-β has been approved for the treatment of relapsing-remitting (RR) multiple sclerosis (MS), whereas its efficacy in preventing long-term disability and conversion to secondary progressive (...

Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis.

Alemtuzumab is a humanised monoclonal antibody that alters the circulating lymphocyte pool, causing prolonged lymphopenia, thus remoulding the immune repertoire that accompanies homeostatic lymphocyte...

Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis.

To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cogn...

Medical and Biotech [MESH] Definitions

A form of multiple sclerosis characterized by a progressive deterioration in neurologic function which is in contrast to the more typical relapsing remitting form. If the clinical course is free of distinct remissions, it is referred to as primary progressive multiple sclerosis. When the progressive decline is punctuated by acute exacerbations, it is referred to as progressive relapsing multiple sclerosis. The term secondary progressive multiple sclerosis is used when relapsing remitting multiple sclerosis evolves into the chronic progressive form. (From Ann Neurol 1994;36 Suppl:S73-S79; Adams et al., Principles of Neurology, 6th ed, pp903-914)

A non-glycosylated form of interferon beta-1 that has a serine at position 17. It is used in the treatment of both RELAPSING-REMITTING MULTIPLE SCLEROSIS and CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS.

A random polymer of L-ALANINE, L-GLUTAMIC ACID, L-LYSINE, and L-TYROSINE that structurally resembles MYELIN BASIC PROTEIN. It is used in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS.

An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)

The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914)

More From BioPortfolio on "Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Antibodies
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...

Spinal Cord Disorders
The spinal cord is a bundle of nerves that runs down the middle of the back which carry signals back and forth between the body and brain. It is protected by vertebrae, which are the bone disks that make up the spine. An accident that damages the verte...


Searches Linking to this Trial