Multiple Sclerosis, Relapsing-RemittingPhase 2NCT00071838
Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis
A Phase 2 study testing Daclizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Daclizumab
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2003to 16 Aug 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
- MEDICAL HISTORY:
- 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:
- Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.
- Total white blood cell count less than 3000/mm(3)
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- Platelet count less than 85000/mm(3)
- Serum creatinine level greater than 2.0 mg/dl
- Serological evidence of HIV or active hepatitis A, B or C infection since the effects of daclizumab are not defined in these patients
- Positive pregnancy test
- 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.
- TREATMENT HISTORY:
- If prior treatments were administered, the patient must be off the following treatment agents for the required period prior to enrollment:
- Glatiramer acetate, interferon-beta - 24 weeks
- IVIg, azathioprine, methotrexate, cyclophosphamide, mitoxantrone, plasma exchange, cyclosporine, oral myelin, cladribine and other immunosuppressive treatments - 24 weeks
- Corticosteroids - 6 weeks
- Prior treatment with other investigational drugs or procedures will be evaluated individually by the investigators.
- MISCELLANEOUS EXCLUSIONS:
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed 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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Daclizumab
- Keywords
- Neuroimmunology, Therapy, Demyelinating Disease, Immunological Mechanism, MRI, Multiple Sclerosis, MS
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Demyelinating Diseases, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in mean number of new gaolinium-enhancing lesions in the treatment phase (Weeks 18 to 30) versus baseline (Weeks -12 to 0).
Secondary outcomes (1)
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...
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2003 (estimated)
- Study start30 Oct 2003
- Primary completion4 Oct 2007
- Study completion16 Aug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00071838
- Sponsor's protocol ID
- 040019
- Other IDs
- 04-N-0019
- Status last verified
- 16 Aug 2011
- First submitted
- 31 Oct 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol. 1992;10:153-87. doi: 10.1146/annurev.iy.10.040192.001101.
PubMed 1375472Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995 Mar 10;80(5):695-705. doi: 10.1016/0092-8674(95)90348-8.
PubMed 7534214Gran B, Hemmer B, Vergelli M, McFarland HF, Martin R. Molecular mimicry and multiple sclerosis: degenerate T-cell recognition and the induction of autoimmunity. Ann Neurol. 1999 May;45(5):559-67. doi: 10.1002/1531-8249(199905)45:53.0.co;2-q.
PubMed 10319877
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00071838
- Acronym / sponsor ID
- 040019
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Neuroimmunology, Therapy, Demyelinating Disease, Immunological Mechanism, MRI, Multiple Sclerosis, MS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 30 Oct 2003
- Primary completion
- 4 Oct 2007 (actual)
- Study completion
- 16 Aug 2011 (actual)
- First posted
- 3 Nov 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
- Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.
- Total white blood cell count less than 3000/mm(3)
- Platelet count less than 85000/mm(3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daclizumab | Drug | – |
Primary outcome
Reduction in mean number of new gaolinium-enhancing lesions in the treatment phase (Weeks 18 to 30) versus baseline (Weeks -12 to 0).
1 secondary outcome
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...
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 1375472Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol. 1992;10:153-87. doi: 10.1146/annurev.iy.10.040192.001101.
- Background: PubMed 7534214Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995 Mar 10;80(5):695-705. doi: 10.1016/0092-8674(95)90348-8.
- Background: PubMed 10319877Gran B, Hemmer B, Vergelli M, McFarland HF, Martin R. Molecular mimicry and multiple sclerosis: degenerate T-cell recognition and the induction of autoimmunity. Ann Neurol. 1999 May;45(5):559-67. doi: 10.1002/1531-8249(199905)45:53.0.co;2-q.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daclizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in mean number of new gaolinium-enhancing lesions in the treatment phase (Weeks 18 to 30) versus baseline (Weeks -12 to 0).. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00071838, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.