Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00076843
Status:
COMPLETED
Last Update Posted:
2019-06-27
First Post:
2006-07-12
Brief Title:
Hu Mik-Beta-1 to Treat HTLV-1-Associated MyelopathyTropical Spastic Paraparesis
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Study of HTLV-I-Associated MyelopathyTropical Spastic Paraparesis HAMTSP Using the Humanized MiK-Beta-1 Monoclonal Antibody Directed Toward the IL-2L-15R-Beta Subunit CD122 That Blocks IL-15 Action
Status:
COMPLETED
Status Verified Date:
2019-06-25
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the use of the humanized Mik-Beta-1 Hu Mik-SqrRoot 1 monoclonal antibody in patients with HTLV-1-associated myelopathytropical spastic paraparesis HAMTSP Some patients infected with the human T-lymphotropic virus type 1 HTLV-1 virus develop HAMTSP a disease in which the immune response to HTLV-1 becomes directed against the persons own body in what is called an autoimmune response Hu-Mik-Beta-1 is a genetically engineered antibody that blocks the action of a chemical produced by the body during infection or inflammation called interleukin 15 IL-15 Blocking IL-15 may prevent the autoimmune response that results in HAMTSP
Patients 18 years of age and older with HAMTSP may be eligible for this study Candidates are screened with a medical history and physical examination blood and urine tests and an electrocardiogram Participants undergo the following procedures
1 Baseline visits Repeat physical examination and blood and urine tests as well as the following
Lumbar puncture A local anesthetic is injected to numb the skin of the lower back A needle is inserted in the space between the bones where the cerebrospinal fluid that bathes the brain and spinal cord circulates below the spinal cord About 4 tablespoons of fluid is collected through the needle
Magnetic resonance imaging MRI This test uses radio waves and magnets to produce images of body tissues and organs The patient lies on a table that slides into a metal cylinder surrounded by a strong magnetic field During part of the scan a contrast agent is injected to brighten the images
Apheresis This procedure is used to collect large quantities of white blood cells Whole blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by spinning The white cells and plasma are removed and the rest of the blood red cells and platelets is returned to the body through the same needle
2 Hu Mik-Beta-1 treatment Infusions of Hu Mik-Beta-1 are given through a vein every 3 weeks for nine doses The first treatment requires at least an overnight hospital stay subsequent infusions are given in the outpatient clinic
3 Blood and urine tests and a physical examination at every treatment visit and a skin test at one treatment visit
4 Research tests at the end of the 24-week treatment period including lumbar puncture spinal tap MRI scan and apheresis
5 After completing treatment patients have three follow-up clinic visits for blood and urine tests and a skin test at one follow-up visit
Patients 18 years of age and older with HAMTSP may be eligible for this study Candidates are screened with a medical history and physical examination blood and urine tests and an electrocardiogram Participants undergo the following procedures
1 Baseline visits Repeat physical examination and blood and urine tests as well as the following
Lumbar puncture A local anesthetic is injected to numb the skin of the lower back A needle is inserted in the space between the bones where the cerebrospinal fluid that bathes the brain and spinal cord circulates below the spinal cord About 4 tablespoons of fluid is collected through the needle
Magnetic resonance imaging MRI This test uses radio waves and magnets to produce images of body tissues and organs The patient lies on a table that slides into a metal cylinder surrounded by a strong magnetic field During part of the scan a contrast agent is injected to brighten the images
Apheresis This procedure is used to collect large quantities of white blood cells Whole blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by spinning The white cells and plasma are removed and the rest of the blood red cells and platelets is returned to the body through the same needle
2 Hu Mik-Beta-1 treatment Infusions of Hu Mik-Beta-1 are given through a vein every 3 weeks for nine doses The first treatment requires at least an overnight hospital stay subsequent infusions are given in the outpatient clinic
3 Blood and urine tests and a physical examination at every treatment visit and a skin test at one treatment visit
4 Research tests at the end of the 24-week treatment period including lumbar puncture spinal tap MRI scan and apheresis
5 After completing treatment patients have three follow-up clinic visits for blood and urine tests and a skin test at one follow-up visit
Detailed Description:
Objectives
In a phase I trial we wish to determine the toxicity and provide preliminary clinical response information following the administration of humanized MiK-beta-1 Hu MiK-Beta1 a monoclonal antibody directed toward IL-2IL-15R Beta CD122 in patients with HTLV-I-associated myelopathytropical spastic paraparesis HAMTSP This antibody blocks the action of IL-15 a cytokine involved in the pathogenesis of HTLV-I associated diseases and autoimmune disorders such as rheumatoid arthritis and multiple sclerosis
Study Population
HAMTSP affects about 1 of patients infected with the human T lymphotropic virus type 1 HTLV-I manifesting as progressive myelopathy Several features of the immune response in HAMTSP indicate that IL-15 may be critical to its pathogenesis HTLV-I transactivates IL-15 and IL-15 R alpha expression through its tax protein and supports the activation of lymphocytes in HAMTSP as evidenced by their spontaneous proliferation in ex vivo culture We showed that the antibody HuMiK-Beta1 could inhibit this spontaneous lymphoproliferation In addition IL-15 has been shown to have a preferential positive effect on the survival of CD8 T-cells especially those of the memory phenotype In HAMTSP an extraordinarily high frequency of tax specific CD8 T-cells in the peripheral blood and cerebrospinal fluid is postulated to participate in the damage to the central nervous system We have demonstrated that the addition of Hu MiK-Beta1 to ex vivo cells from HAMTSP patients led to a marked decline in tax specific CD8 T-cells
Design of the Study and Outcome Parameters
In this single center open label trial four subjects with HAMTSP will receive 05 mgkg Hu MiK-beta1 dosed every three weeks for a total of five doses and two subjects with HAMTSP will receive placebo normal saline under the same dosing schedule In addition following the completion of the 05 mgkg dose administration in four subjects with HAMTSP a dose escalation study will be performed with three subjects with HAMTSP receiving 10 mgkg of Hu MiK-beta1 at three week intervals for a total of five doses per subject and three subjects with HAMTSP receiving 15 mgkg of Hu MiK-beta1 at three week intervals for a total of five doses per subject A Total of 10 subjects will receive study drugplacebo We anticipate consenting up to eighteen subjects to allow for up to eight dropouts Participants who withdraw voluntarily not due to toxicity after initiation of the study are considered dropouts If this occurs prior to receiving three doses of the study medication the subjects can be replaced and should have three follow-up evaluations at four-week intervals following the last dose of the study drug Patients who voluntarily drop out after receiving at least 3 doses of the study drug will remain in the study and continue the protocol-specific evaluations Toxicity will be assessed using standard criteria The clinical response will be evaluated using standardized scales including expanded disability status scale Scripps neurologic rating scale and ambulation index In addition viral and immunologic outcome measures will include assays of spontaneous lymphoproliferation analysis of HTLV-I tax tetramer specific CD8 cells HTLV-I proviral load determination and T-cell phenotype analysis
In a phase I trial we wish to determine the toxicity and provide preliminary clinical response information following the administration of humanized MiK-beta-1 Hu MiK-Beta1 a monoclonal antibody directed toward IL-2IL-15R Beta CD122 in patients with HTLV-I-associated myelopathytropical spastic paraparesis HAMTSP This antibody blocks the action of IL-15 a cytokine involved in the pathogenesis of HTLV-I associated diseases and autoimmune disorders such as rheumatoid arthritis and multiple sclerosis
Study Population
HAMTSP affects about 1 of patients infected with the human T lymphotropic virus type 1 HTLV-I manifesting as progressive myelopathy Several features of the immune response in HAMTSP indicate that IL-15 may be critical to its pathogenesis HTLV-I transactivates IL-15 and IL-15 R alpha expression through its tax protein and supports the activation of lymphocytes in HAMTSP as evidenced by their spontaneous proliferation in ex vivo culture We showed that the antibody HuMiK-Beta1 could inhibit this spontaneous lymphoproliferation In addition IL-15 has been shown to have a preferential positive effect on the survival of CD8 T-cells especially those of the memory phenotype In HAMTSP an extraordinarily high frequency of tax specific CD8 T-cells in the peripheral blood and cerebrospinal fluid is postulated to participate in the damage to the central nervous system We have demonstrated that the addition of Hu MiK-Beta1 to ex vivo cells from HAMTSP patients led to a marked decline in tax specific CD8 T-cells
Design of the Study and Outcome Parameters
In this single center open label trial four subjects with HAMTSP will receive 05 mgkg Hu MiK-beta1 dosed every three weeks for a total of five doses and two subjects with HAMTSP will receive placebo normal saline under the same dosing schedule In addition following the completion of the 05 mgkg dose administration in four subjects with HAMTSP a dose escalation study will be performed with three subjects with HAMTSP receiving 10 mgkg of Hu MiK-beta1 at three week intervals for a total of five doses per subject and three subjects with HAMTSP receiving 15 mgkg of Hu MiK-beta1 at three week intervals for a total of five doses per subject A Total of 10 subjects will receive study drugplacebo We anticipate consenting up to eighteen subjects to allow for up to eight dropouts Participants who withdraw voluntarily not due to toxicity after initiation of the study are considered dropouts If this occurs prior to receiving three doses of the study medication the subjects can be replaced and should have three follow-up evaluations at four-week intervals following the last dose of the study drug Patients who voluntarily drop out after receiving at least 3 doses of the study drug will remain in the study and continue the protocol-specific evaluations Toxicity will be assessed using standard criteria The clinical response will be evaluated using standardized scales including expanded disability status scale Scripps neurologic rating scale and ambulation index In addition viral and immunologic outcome measures will include assays of spontaneous lymphoproliferation analysis of HTLV-I tax tetramer specific CD8 cells HTLV-I proviral load determination and T-cell phenotype analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-N-0071 | None | None | None |