Multiple SclerosisPhase 2NCT00001934
Zenapax to Treat Multiple Sclerosis
A Phase 2 study testing Zenapax in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of Zenapax (a laboratory-manufactured antibody) in treating multiple sclerosis. Multiple sclerosis may be caused by an abnormal immune response in which white blood cells called T lymphocytes attack the myelin sheath that covers nerves and parts of the spinal cord. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Zenapax
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1999to Sep 2008
- 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
- Between the ages of 18 and 65 years, inclusive.
- Subjects with relapsing-remitting or secondary progressive Multiple Sclerosis who have had more than 1 relapse within 18 months preceding study enrollment.
- EDSS score between 1 - 6.5, inclusive.
- Give written informed consent prior to any testing under this protocol, including screening/pre-treatment tests and evaluations that are not considered part of the subject's routine care.
- Patients who have failed standard IFN-beta therapy.
- To be eligible to proceed to the treatment phase of the study, subjects must have at least 2 Gd-enhancing lesions or greater in the 3 pre-treatment MRI scans (an average of at least 0.67 Gd-enhancing lesions per scan).
- In patients with high inflammatory activity and high relapse rates it has been our experience that the requirement of steroid therapy for the treatment of relapses may prolong the baseline phase. In patients with high disease activity who require steroid therapy and quickly afterwards demonstrate disease activity again, the investigator retains the option to enroll patients with less than the stipulated baseline months in order to initiate daclizumab therapy as quickly as possible. Since treatment escalation would otherwise require therapy with mitoxantrone or cyclophosphamide, which both have substantial toxicity, this step is in the best interest of the patient.
Who cannot join
- Diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses.
- Abnormal screening/pre-treatment blood tests exceeding any of the limits defined below:
- Alanine transaminase (ALT) or aspartate transaminase (AST) greater than two times the upper limit of normal;
- Total white blood cell count less than 3,000/mm(3);
- CD4+ count less than 320/mm(3);
- Platelet count less than 80,000/mm(3);
Show all 18Show fewer
- Creatinine greater than 2.0 mg/dL.
- Concurrent, clinically significant (as determined by the investigator) cardiac, immunologic, pulmonary, neurologic, renal, and/or other major disease.
- Any contraindication to monoclonal antibody therapies.
- Patients who are HIV+ since the effects of anti-Tac are not defined in these patients.
- If prior treatment was received, the subject must have been off treatment for the required period prior to enrollment.
- Prior treatment with any other investigational drug or procedure for MS.
- History of alcohol or drug abuse within the 5 years prior to enrollment.
- Male and female subjects not practicing adequate contraception.
- Female subjects who are not post-menopausal or surgically sterile must be using an acceptable method of contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Written documentation that the subject is post-menopausal or surgically sterile must be available prior to study start.
- 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 subject's returning for follow-up visits on schedule.
- Previous participation in this study.
- Breastfeeding patients.
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: Effect of the Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (IL-2R-Alpha; Zenapax(Registered Trademark)) on Inflammatory Activity in the CNS in MS in a Baseline-to-Treatment, Cross-Over, MRI-Controlled Single Center Phase I/II Trial
This study will examine the safety and effectiveness of Zenapax (a laboratory-manufactured antibody) in treating multiple sclerosis. Multiple sclerosis may be caused by an abnormal immune response in which white blood cells called T lymphocytes attack the myelin sheath that covers nerves and parts of the spinal cord. Zenapax binds to protein receptors on lymphocytes, keeping them from interacting with interleukin-2, a substance necessary for their growth.
Patients with multiple sclerosis who have had at least one relapse within 18 months of the start of the study and in whom interferon-beta treatment has not been successful may be considered for this study. There are two study phases: baseline and treatment. During the baseline phase, patients will have three magnetic resonance imaging (MRI) scans over 2 months to evaluate their disease activity. During treatment, patients will receive seven intravenous (I.V.) infusions of Zenapax in the clinic. The first two infusions will be given 2 weeks apart; the next five will be given once a month.
Read more
Patients will have MRI scans before each infusion. The MRIs will be done using the standard procedure and again using a contrast agent, gadolinium, injected into a vein. Gadolinium helps identify new multiple sclerosis lesions in the brain. Blood and urine samples will be taken during each clinic visit. In addition, patients will have skin tests, similar to a tuberculin test, to evaluate immune status, and will be asked to undergo two lumbar punctures (spinal tap; these will be optional)-one before the treatment phase begins, and another when treatment is completed. Lymphocytes will also be collected from patients before, during and after treatment. The lymphocytes are obtained by a procedure called apheresis: about a pint of whole blood is drawn through a needle in the arm, the lymphocytes are separated out and removed by a machine, and the rest of the blood is returned through a needle in the other arm. These studies will hopefully allow conclusions about the safety of Zenapax in MS, but also address its effectiveness with respect to modifying the inflammatory activity in the brain of MS patients and inhibit autoimmune T lymphocytes that are involved in the disease process.
...
Read the detailed description
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that preferentially affects young adults. While its etiology is unknown, current concepts assume that CD4+ helper T cells with specificity for components of the myelin sheath initiate the pathogenetic process. The activation and expansion of such autoreactive T cells involves the secretion of autocrine growth factors, particularly interleukin-2 (IL-2), and the concomitant expression of its receptor, IL-2R, on the surface of T cells. Since only activated T lymphocytes can migrate through the blood brain barrier into the CNS and induce the inflammatory process, blocking the IL-2R should have an impact on disease activity in MS.
In this trial , a humanized antibody against the IL-2Ra subunit (Zenapax(Registered Trademark)) will be used to inhibit T cell activation in MS patients who have failed conventional therapy by interferon-b. We will focus on the latter group of patients, since a substantial number of patients on conventional therapy respond only partially or completely fail treatment after longer periods of time. Up to 10 patients fulfilling these criteria will be enrolled in this baseline-to-treatment, cross-over, MRI-controlled single-center phase I/II trial to assess the safety of Zenapax(Registered Trademark) treatment and, at the same time, examine the clinical course and particularly the inflammatory activity in the CNS by monthly magnetic resonance imaging (MRI). Furthermore, immunological studies will be performed in parallel to the trial in order to a) identify the impact of Zenapax(Registered Trademark) treatment on immune parameters that should be affected by the blocking of the IL-2R, and b) to improve our understanding of the relevance of activated autoreactive T lymphocytes in MS.
- Conditions
- Multiple Sclerosis
- Being tested
- Zenapax
- Keywords
- Multiple Sclerosis, Immunotherapy, MRI
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZenapaxDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in contrast-enhancing lesions on brain MRI.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startSep 1999
- Primary completionAug 2005
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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
- 22 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001934
- Sponsor's protocol ID
- 990169
- Other IDs
- 99-N-0169
- Status last verified
- Aug 2011
- First submitted
- 3 Nov 1999
- Last updated
- 5 Aug 2011
- 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 10319877Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol. 2009 Apr;66(4):483-9. doi: 10.1001/archneurol.2009.50.
PubMed 19364933
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (IL-2R-Alpha; Zenapax(Registered Trademark)) on Inflammatory Activity in the CNS in MS in a Baseline-to-Treatment, Cross-Over, MRI-Controlled Single Center Phase I/II Trial
- ClinicalTrials.gov ID
- NCT00001934
- Acronym / sponsor ID
- 990169
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Immunotherapy, MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Sep 1999
- Primary completion
- Aug 2005 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 4 Nov 1999 (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 and effectiveness of Zenapax (a laboratory-manufactured antibody) in treating multiple sclerosis. Multiple sclerosis may be caused by an abnormal immune response in which white blood cells called T lymphocytes attack the myelin sheath that covers nerves and parts of the spinal cord. Zenapax binds to protein receptors on lymphocytes, keeping them from interacting with interleukin-2, a substance necessary for their growth.
Patients with multiple sclerosis who have had at least one relapse within 18 months of the start of the study and in whom interferon-beta treatment has not been successful may be considered for this study. There are two study phases: baseline and treatment. During the baseline phase, patients will have three magnetic resonance imaging (MRI) scans over 2 months to evaluate their disease activity. During treatment, patients will receive seven intravenous (I.V.) infusions of Zenapax in the clinic. The first two infusions will be given 2 weeks apart; the next five will be given once a month.
Patients will have MRI scans before each infusion. The MRIs will be done using the standard procedure and again using a contrast agent, gadolinium, injected into a vein. Gadolinium helps identify new multiple sclerosis lesions in the brain. Blood and urine samples will be taken during each clinic visit. In addition, patients will have skin tests, similar to a tuberculin test, to evaluate immune status, and will be asked to undergo two lumbar punctures (spinal tap; these will be optional)-one before the treatment phase begins, and another when treatment is completed. Lymphocytes will also be collected from patients before, during and after treatment. The lymphocytes are obtained by a procedure called apheresis: about a pint of whole blood is drawn through a needle in the arm, the lymphocytes are separated out and removed by a machine, and the rest of the blood is returned through a needle in the other arm. These studies will hopefully allow conclusions about the safety of Zenapax in MS, but also address its effectiveness with respect to modifying the inflammatory activity in the brain of MS patients and inhibit autoimmune T lymphocytes that are involved in the disease process.
...
Detailed description
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that preferentially affects young adults. While its etiology is unknown, current concepts assume that CD4+ helper T cells with specificity for components of the myelin sheath initiate the pathogenetic process. The activation and expansion of such autoreactive T cells involves the secretion of autocrine growth factors, particularly interleukin-2 (IL-2), and the concomitant expression of its receptor, IL-2R, on the surface of T cells. Since only activated T lymphocytes can migrate through the blood brain barrier into the CNS and induce the inflammatory process, blocking the IL-2R should have an impact on disease activity in MS.
In this trial , a humanized antibody against the IL-2Ra subunit (Zenapax(Registered Trademark)) will be used to inhibit T cell activation in MS patients who have failed conventional therapy by interferon-b. We will focus on the latter group of patients, since a substantial number of patients on conventional therapy respond only partially or completely fail treatment after longer periods of time. Up to 10 patients fulfilling these criteria will be enrolled in this baseline-to-treatment, cross-over, MRI-controlled single-center phase I/II trial to assess the safety of Zenapax(Registered Trademark) treatment and, at the same time, examine the clinical course and particularly the inflammatory activity in the CNS by monthly magnetic resonance imaging (MRI). Furthermore, immunological studies will be performed in parallel to the trial in order to a) identify the impact of Zenapax(Registered Trademark) treatment on immune parameters that should be affected by the blocking of the IL-2R, and b) to improve our understanding of the relevance of activated autoreactive T lymphocytes in 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 (7 listed)
- Between the ages of 18 and 65 years, inclusive.
- Subjects with relapsing-remitting or secondary progressive Multiple Sclerosis who have had more than 1 relapse within 18 months preceding study enrollment.
- EDSS score between 1 - 6.5, inclusive.
- Give written informed consent prior to any testing under this protocol, including screening/pre-treatment tests and evaluations that are not considered part of the subject's routine care.
- Patients who have failed standard IFN-beta therapy.
Key exclusion criteria (18 listed)
- Diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses.
- Alanine transaminase (ALT) or aspartate transaminase (AST) greater than two times the upper limit of normal;
- Total white blood cell count less than 3,000/mm(3);
- CD4+ count less than 320/mm(3);
- Platelet count less than 80,000/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 |
|---|---|---|
| Zenapax | Drug | – |
Primary outcome
Change in contrast-enhancing lesions on brain MRI.
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 5 Aug 2011.
- 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.
- Derived from this study: PubMed 19364933Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol. 2009 Apr;66(4):483-9. doi: 10.1001/archneurol.2009.50.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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 Zenapax in people with Multiple Sclerosis, 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 7 inclusion and 18 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 5 Aug 2011. 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?
Change in contrast-enhancing lesions on brain MRI.. 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 NCT00001934, which also lists 4 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 5 Aug 2011.