Wise Young
08-06-2001, 01:43 AM
http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00001934?order=49&JServSession Idzone_ct=zhn5b9gan1 (http://clinicaltrials.gov/ct/gui/c/a1b/show/NCT00001934?order=49&JServSessionIdzone_ct=zhn5b9gan1)
Zenapax to Treat Multiple Sclerosis
This study is currently recruiting patients.
Sponsored by
National Institute of Neurological Disorders and Stroke (NINDS)
Purpose
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.
Condition Phase
Multiple Sclerosis
Phase II
MEDLINEplusrelated topics:MultipleSclerosis
Study Type:Clinical Trial
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
Further Study Details:
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.
Eligibility
Genders Eligible for Study: Both
Criteria
Between the ages of 18 and 65 years, inclusive. Subjects with relapsing-remitting or secondary progressive Multiple Sclerosis (EDSS range 2.5 - 6.5) who have failed standard IFN-Beta treatment based on one or more exacerbations in the last 18 months or progression reflected by a change of 1 point or more in EDSS over 18 months or signs of disease activity by MRI that indicate treatment failure or based on a persistence or recurrence of Gd-contrasting MRI lesions to at least half the mean of baseline monthly Gd-contrasting lesions over 6 months before onset of IFN treatment. EDSS score between 2.5 - 6.5, inclusive. Must 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. Must not have a diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses. Must not have 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);
Creatinine greater than 2.0 mg/dL.
Must not have concurrent, clinically significant (as determined by the investigator) cardiac, immunologic, pulmonary, neurologic, renal, and/or other major disease. No contraindication to monoclonal antibody therapies. Must not be HIV positive.
If prior treatment was received, the subject must have been off treatment for the required period prior to enrollment. Must not have had prior treatment with any other investigational drug or procedure for MS. The decision to exclude a patient according to this criteria will be based on the mechanism of action of the investigational drug or procedure and will be at the discretion of the investigators. No history of alcohol or drug abuse within the 5 years prior to enrollment. Male and female subjects must practice adequate contraception. Female subjects who are not post-menopausal or surgically sterile must be using an acceptable method of contraception. Must not be breastfeeding. Must be willing and able 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. Must not have previously participated in this study.
Location and Contact Information
Maryland
National Institute of Neurological Disorders and Stroke (NINDS),9000 Rockville Pike Bethesda, Maryland, 20892, United States;Recruiting
PRPL 1-800-411-1222 prpl@mail.cc.nih.gov
More Information
Detailed Web Page
Publications
Martin. 1992. Immunological aspects of demyelinating diseases, Annu Rev Immunol, Vol. 10, p. 153
Wucherpfennig. 1995. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein, Cell, Vol. 80, p. 695
Gran. 1999. Molecular mimicry and multiple sclerosis: degenerate T-cell recognition and the induction of autoimmunity, Ann Neurol, Vol. 45, p. 559
Study ID Numbers 99-N-0169
NLM Identifier NCT00001934
Date study startedSeptember 3, 1999
Record last reviewed August 17, 2000
Last Updated August 17, 2000
[This message was edited by Wise Young on August 06, 2001 at 12:29 PM.]
Zenapax to Treat Multiple Sclerosis
This study is currently recruiting patients.
Sponsored by
National Institute of Neurological Disorders and Stroke (NINDS)
Purpose
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.
Condition Phase
Multiple Sclerosis
Phase II
MEDLINEplusrelated topics:MultipleSclerosis
Study Type:Clinical Trial
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
Further Study Details:
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.
Eligibility
Genders Eligible for Study: Both
Criteria
Between the ages of 18 and 65 years, inclusive. Subjects with relapsing-remitting or secondary progressive Multiple Sclerosis (EDSS range 2.5 - 6.5) who have failed standard IFN-Beta treatment based on one or more exacerbations in the last 18 months or progression reflected by a change of 1 point or more in EDSS over 18 months or signs of disease activity by MRI that indicate treatment failure or based on a persistence or recurrence of Gd-contrasting MRI lesions to at least half the mean of baseline monthly Gd-contrasting lesions over 6 months before onset of IFN treatment. EDSS score between 2.5 - 6.5, inclusive. Must 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. Must not have a diagnosis of primary progressive MS, defined as gradual progression of disability from the onset without relapses. Must not have 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);
Creatinine greater than 2.0 mg/dL.
Must not have concurrent, clinically significant (as determined by the investigator) cardiac, immunologic, pulmonary, neurologic, renal, and/or other major disease. No contraindication to monoclonal antibody therapies. Must not be HIV positive.
If prior treatment was received, the subject must have been off treatment for the required period prior to enrollment. Must not have had prior treatment with any other investigational drug or procedure for MS. The decision to exclude a patient according to this criteria will be based on the mechanism of action of the investigational drug or procedure and will be at the discretion of the investigators. No history of alcohol or drug abuse within the 5 years prior to enrollment. Male and female subjects must practice adequate contraception. Female subjects who are not post-menopausal or surgically sterile must be using an acceptable method of contraception. Must not be breastfeeding. Must be willing and able 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. Must not have previously participated in this study.
Location and Contact Information
Maryland
National Institute of Neurological Disorders and Stroke (NINDS),9000 Rockville Pike Bethesda, Maryland, 20892, United States;Recruiting
PRPL 1-800-411-1222 prpl@mail.cc.nih.gov
More Information
Detailed Web Page
Publications
Martin. 1992. Immunological aspects of demyelinating diseases, Annu Rev Immunol, Vol. 10, p. 153
Wucherpfennig. 1995. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein, Cell, Vol. 80, p. 695
Gran. 1999. Molecular mimicry and multiple sclerosis: degenerate T-cell recognition and the induction of autoimmunity, Ann Neurol, Vol. 45, p. 559
Study ID Numbers 99-N-0169
NLM Identifier NCT00001934
Date study startedSeptember 3, 1999
Record last reviewed August 17, 2000
Last Updated August 17, 2000
[This message was edited by Wise Young on August 06, 2001 at 12:29 PM.]