Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00024934
Status:
COMPLETED
Last Update Posted:
2016-09-22
First Post:
2001-10-09
Brief Title:
B-Lymphocyte Stimulator BLyS To Treat Selective IgA Deficiency
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Dose Escalation Study of B-Lymphocyte Stimulator BLyS Administered Subcutaneously in Patients With Selective IgA Deficiency
Status:
COMPLETED
Status Verified Date:
2016-09
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 safety of BlyS an experimental drug being developed to treat immune deficiency As of July 17 2001 7 persons with common variable immune deficiency CVID have received BlyS with no problems reported This study will test the safety of the drug in people with IgA deficiency
Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study Candidates will be screened with a physical examination blood and urine tests electrocardiogram EKG chest X-ray and a breathing test spirometry
Participants will be divided into five groups of three persons each to receive different doses 01 1 5 15 or 45 microgramskilogram of body weight of BlyS The first group will receive a single dose at the lowest dose level 0l mg Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group The drug will be injected under the skin with vital signs temperature pulse blood pressure and breathing rate monitored for one hour after dosing Blood samples will be collected several times on the day of dosing before the dose and at 15 3 5 8 and 12 hours after the dose and again at 12 4 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety Participants receiving one of the three higher doses will have additional blood samples collected 36 48 and 60 hours after the dose Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects A total of 289 ml 12 cups of blood will be collected
Blood will be checked for changes in blood count kidney and liver function antibody levels and autoimmune problems Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels
Urine samples will also be collected during the study
Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study Candidates will be screened with a physical examination blood and urine tests electrocardiogram EKG chest X-ray and a breathing test spirometry
Participants will be divided into five groups of three persons each to receive different doses 01 1 5 15 or 45 microgramskilogram of body weight of BlyS The first group will receive a single dose at the lowest dose level 0l mg Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group The drug will be injected under the skin with vital signs temperature pulse blood pressure and breathing rate monitored for one hour after dosing Blood samples will be collected several times on the day of dosing before the dose and at 15 3 5 8 and 12 hours after the dose and again at 12 4 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety Participants receiving one of the three higher doses will have additional blood samples collected 36 48 and 60 hours after the dose Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects A total of 289 ml 12 cups of blood will be collected
Blood will be checked for changes in blood count kidney and liver function antibody levels and autoimmune problems Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels
Urine samples will also be collected during the study
Detailed Description:
B Lymphocyte Stimulator BLyS Trademark is a member of the tumor necrosis factor TNF superfamily of cytokines that is expressed on peripheral blood monocytes and dendritic cells Cellular receptors for BLyS are detected on mature immunoglobulin Ig expressing B-lymphocytes In vitro studies show that BLyS increases B cell number Ig production antigen-specific immunoglobulin response and induces production of secretory IgA
B-cells collected from patients with Common Variable Immune Deficiency show evidence for BLyS binding to B cells and enhanced immunoglobulin secretion
In 28-day toxicology studies in mice pharmacological effects were restricted to B lymphoid tissues including B lymphocyte hyperplasia increased splenic weight without significant increase in spleen size and increased immunoglobulin production Murine models suggest that all of the pharmacological effects are fully and rapidly reversible
The biological profile of BLyS suggests that it may have therapeutic utility in the treatment of immunodeficiency disorders characterized by low or absent immunoglobulin such as selective IgA deficiency IGA-D
Risk that BLyS might contribute to IGA-D complications has been assessed A series of special in vitro and short-term in vivo studies have shown BLyS does not enhance tumorigenicity or allergyhypersensitivity Enhanced autoimmunity with immune complex formation could not be ruled out in two mouse studies in which BLyS was administered at higher doses on multiple dosing schedules Renal changes with glomerular protein deposits were noted in a subset of mice treated at 01 and 10 mgkg in the first study and 03 and 30 mgkg in the second study Renal changes have not been reproducible in either of 2 repeat mouse studies designed to replicate conditions on the first study Renal changes were not observed in the GLP toxicity study in which mice were treated for 4 weeks with BLyS followed by a 2-week recovery period or in an exploratory monkey study
This study is a phase I single-dose open-label non-randomized dose escalation study of BLyS administered subcutaneously to a total of 20 evaluable subjects with IgA-D Each subject will receive a single dose of BLyS
The proposed study consists of a screening phase a 1-day treatment phase with pharmacokinetic sampling day 2 and day 3 follow-up and 1 2 4 8 and 12-week acute safety evaluations Dose escalation to the next cohort is dependent on results of the 2-week acute safety evaluation Autoimmunity and interim infection history will be evaluated 4-6 weeks and 6 and 12 months Long-term data will be collected on incidence of malignancy for a minimum of one year
B-cells collected from patients with Common Variable Immune Deficiency show evidence for BLyS binding to B cells and enhanced immunoglobulin secretion
In 28-day toxicology studies in mice pharmacological effects were restricted to B lymphoid tissues including B lymphocyte hyperplasia increased splenic weight without significant increase in spleen size and increased immunoglobulin production Murine models suggest that all of the pharmacological effects are fully and rapidly reversible
The biological profile of BLyS suggests that it may have therapeutic utility in the treatment of immunodeficiency disorders characterized by low or absent immunoglobulin such as selective IgA deficiency IGA-D
Risk that BLyS might contribute to IGA-D complications has been assessed A series of special in vitro and short-term in vivo studies have shown BLyS does not enhance tumorigenicity or allergyhypersensitivity Enhanced autoimmunity with immune complex formation could not be ruled out in two mouse studies in which BLyS was administered at higher doses on multiple dosing schedules Renal changes with glomerular protein deposits were noted in a subset of mice treated at 01 and 10 mgkg in the first study and 03 and 30 mgkg in the second study Renal changes have not been reproducible in either of 2 repeat mouse studies designed to replicate conditions on the first study Renal changes were not observed in the GLP toxicity study in which mice were treated for 4 weeks with BLyS followed by a 2-week recovery period or in an exploratory monkey study
This study is a phase I single-dose open-label non-randomized dose escalation study of BLyS administered subcutaneously to a total of 20 evaluable subjects with IgA-D Each subject will receive a single dose of BLyS
The proposed study consists of a screening phase a 1-day treatment phase with pharmacokinetic sampling day 2 and day 3 follow-up and 1 2 4 8 and 12-week acute safety evaluations Dose escalation to the next cohort is dependent on results of the 2-week acute safety evaluation Autoimmunity and interim infection history will be evaluated 4-6 weeks and 6 and 12 months Long-term data will be collected on incidence of malignancy for a minimum of one year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 02-C-0009 | None | None | None |