Ignite Creation Date:
2025-12-24 @ 2:38 PM
Ignite Modification Date:
2025-12-25 @ 2:32 PM
Study NCT ID:
NCT00070759
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2003-10-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Daclizumab to Treat Non-Infectious Sight-Threatening Uveitis
Sponsor:
National Eye Institute (NEI)
Organization:
Study Overview
Official Title:
Daclizumab for Active, Non-infectious, Sight-threatening Uveitis: A Phase II Pilot Study
Status:
COMPLETED
Status Verified Date:
2006-10-02
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 and effectiveness of treating uveitis, an eye inflammation, with a monoclonal antibody called daclizumab. Monoclonal antibodies are genetically engineered proteins made in large quantities and directed against a specific target in the body. Daclizumab is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. In an ongoing NIH study of 10 adults with uveitis, 8 patients were able to decrease corticosteroids and other immunosuppressive medicines they were taking while receiving daclizumab for months or even years. Seven patients continue to take the drug.
Patients 18 years of age and older with active non-infectious intermediate or posterior uveitis in both eyes who require treatment for their disease may be eligible for this study. Candidates will be screened with the following tests and procedures:
* Medical history and physical examination.
* Eye examination to measure visual acuity and eye pressure, and examine the lens, retina, pupils and eye movements.
* Blood tests to measure the number and types of blood cells.
* Fluorescein angiography to check for abnormalities of eye blood vessels. A yellow dye injected into an arm vein travels to the blood vessels in the eyes. Pictures of the retina are taken with a special camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible abnormalities.
Participants come to the NIH Clinical Center for treatment and follow-up visits. The first daclizumab treatment is given as a 90-minute infusion through a vein. A second IV infusion is given 7 days later. If the treatment has successfully reduced the eye inflammation after 2 weeks, then subsequent treatments are given through injections under the skin once a month for up to 1 year. Patients whose eye disease is not improved after 2 weeks stop the study treatments and receive alternative therapy.
Follow-up visits are scheduled 7, 14, and 21 days after enrollment and at each treatment visit to evaluate the response to treatment and drug side effects. During these visits, patients repeat the exams done at screening. Extra blood samples are taken at certain visits to measure blood levels of daclizumab and to perform clinical laboratory and immunology tests. Fluorescein angiography is done at enrollment and after 1 year.
Patients 18 years of age and older with active non-infectious intermediate or posterior uveitis in both eyes who require treatment for their disease may be eligible for this study. Candidates will be screened with the following tests and procedures:
* Medical history and physical examination.
* Eye examination to measure visual acuity and eye pressure, and examine the lens, retina, pupils and eye movements.
* Blood tests to measure the number and types of blood cells.
* Fluorescein angiography to check for abnormalities of eye blood vessels. A yellow dye injected into an arm vein travels to the blood vessels in the eyes. Pictures of the retina are taken with a special camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible abnormalities.
Participants come to the NIH Clinical Center for treatment and follow-up visits. The first daclizumab treatment is given as a 90-minute infusion through a vein. A second IV infusion is given 7 days later. If the treatment has successfully reduced the eye inflammation after 2 weeks, then subsequent treatments are given through injections under the skin once a month for up to 1 year. Patients whose eye disease is not improved after 2 weeks stop the study treatments and receive alternative therapy.
Follow-up visits are scheduled 7, 14, and 21 days after enrollment and at each treatment visit to evaluate the response to treatment and drug side effects. During these visits, patients repeat the exams done at screening. Extra blood samples are taken at certain visits to measure blood levels of daclizumab and to perform clinical laboratory and immunology tests. Fluorescein angiography is done at enrollment and after 1 year.
Detailed Description:
Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications used for uveitis can cause significant toxic side effects, especially with prolonged use. Consequently, an effective treatment with a safer side effect profile is highly desirable. Daclizumab is a humanized monoclonal antibody directed against the high affinity IL-2 receptor CD25 or Tac subunit. The IL-2 receptor system plays a central role in mediating immune responses. Blocking this system impedes immune responses and can inhibit local inflammatory responses, including uveitis. Pilot studies using intravenous or subcutaneous daclizumab treatments suggest that daclizumab treatments at 1 mg/kg every 2-4 weeks for quiescent uveitis may effectively replace the other immunosuppressive medications in a majority of cases.
Because we have little experience using daclizumab for active uveitis, this feasibility study will enroll five study participants that would normally be treated with systemic, high-dose corticosteroids or other cytotoxic, systemic immunosuppressive medications. Since daclizumab for other indications can be tolerated with repeated dosing at 8-10 mg/kg, we will administer daclizumab to reach high serum levels with a pair doses at 8 mg/kg and 4 mg/kg two weeks apart. The primary objective of this study is to collect preliminary information on the utility of acute daclizumab therapy on active ocular inflammation. The primary outcome is resolution of active disease defined as the reduction of vitreous haze by at least 2 steps (from 2+ to Trace, or 1+ to none) and is assessed at 21 days after the initial daclizumab injection. Secondary outcomes will include fluorescein retinal vascular leakage, CME, anterior chamber cells, and visual acuity. In addition all adverse events will be collected regardless of possible relation to daclizumab. Participants who show a 2 step reduction in vitreous haze at day 21 will be permitted to continue SC daclizumab maintenance treatments beginning at Day 28 at 2 mg/kg every 4 weeks for a year. At any time during the followup period, if a participant loses greater than 3 lines of visual acuity from baseline study treatments will be discontinued.
Because we have little experience using daclizumab for active uveitis, this feasibility study will enroll five study participants that would normally be treated with systemic, high-dose corticosteroids or other cytotoxic, systemic immunosuppressive medications. Since daclizumab for other indications can be tolerated with repeated dosing at 8-10 mg/kg, we will administer daclizumab to reach high serum levels with a pair doses at 8 mg/kg and 4 mg/kg two weeks apart. The primary objective of this study is to collect preliminary information on the utility of acute daclizumab therapy on active ocular inflammation. The primary outcome is resolution of active disease defined as the reduction of vitreous haze by at least 2 steps (from 2+ to Trace, or 1+ to none) and is assessed at 21 days after the initial daclizumab injection. Secondary outcomes will include fluorescein retinal vascular leakage, CME, anterior chamber cells, and visual acuity. In addition all adverse events will be collected regardless of possible relation to daclizumab. Participants who show a 2 step reduction in vitreous haze at day 21 will be permitted to continue SC daclizumab maintenance treatments beginning at Day 28 at 2 mg/kg every 4 weeks for a year. At any time during the followup period, if a participant loses greater than 3 lines of visual acuity from baseline study treatments will be discontinued.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 04-EI-0006 | None | None | View |