ANTI-TAC THERAPY FOR UVEITIS

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001526
First received: November 3, 1999
Last updated: September 7, 2007
Last verified: September 2007
  Purpose

Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable.

This pilot study has permitted enrollment of up to 12 adults with non-infectious intermediate or posterior uveitis who require treatments to maintain visual function. This extended protocol began with an evaluation of the safety and potential efficacy of intravenous (IV) daclizumab treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. As subcutaneous (SC) daclizumab treatments become available, eligible participants will be offered continuing daclizumab treatments using the new SC formulation, though they may elect to remain on the IV treatments. If the therapeutic benefit is sustained using the SC formulation, maintenance therapy will continue as clinically indicated. Participants who repeatedly fail the SC therapy will be permitted to revert to the IV daclizumab regimen they previously used, or may exit the study as treatment failures. SC treatments begin with a short SC induction at 2 mg/kg followed by 1 mg/kg treatments on a 4-week schedule as the protocol originally specified. Participants will be monitored routinely when each dose is received and additionally will participate in pharmacokinetic studies to monitor SC formulation bioavailability.

Daclizumab is a humanized anti-Tac monoclonal antibody (HAT, Zenapax) that interferes with inflammatory processes by its involvement with the interleukin 2 receptor (IL-2R). During the first 5 years of this study, only an IV product was available. The SC formulation is now available containing the same daclizumab drug product. Preliminary studies indicate that the SC formulation is well tolerated by normal control subjects and other autoimmune disease patients at repeated doses up to 2 mg/kg.

The primary objectives are to examine the safety and potential efficacy of IV and later, SC daclizumab, while continuing to reduce other immunosuppressive medications commensurate with the standard of care. Primary safety outcomes are the discontinuation of study therapy due to reduced vision or the occurrence of adverse events. Secondary outcome measures include visual acuity and the grading of immunosuppressive medications, anterior chamber and vitreous cells, and vitreous haze.


Condition Intervention Phase
Uveitis
Drug: Daclizumab (Zenapax)
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Trial of Treatment of Non-Infectious Intermediate and Posterior Uveitis With Humanized Anti-Tac Antibody Therapy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 15
Study Start Date: June 1996
Estimated Study Completion Date: September 2007
Detailed Description:

Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable.

This pilot study has permitted enrollment of up to 12 adults with non-infectious intermediate or posterior uveitis who require treatments to maintain visual function. This extended protocol began with an evaluation of the safety and potential efficacy of intravenous (IV) daclizumab treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. As subcutaneous (SC) daclizumab treatments become available, eligible participants will be offered continuing daclizumab treatments using the new SC formulation, though they may elect to remain on the IV treatments. If the therapeutic benefit is sustained using the SC formulation, maintenance therapy will continue as clinically indicated. Participants who repeatedly fail the SC therapy will be permitted to revert to the IV daclizumab regimen they previously used, or may exit the study as treatment failures. SC treatments begin with a short SC induction at 2 mg/kg followed by 1 mg/kg treatments on a 4-week schedule as the protocol originally specified. Participants will be monitored routinely when each dose is received and additionally will participate in pharmacokinetic studies to monitor SC formulation bioavailability.

Daclizumab is a humanized anti-Tac monoclonal antibody (HAT, Zenapax) that interferes with inflammatory processes by its involvement with the interleukin 2 receptor (IL-2R). During the first 5 years of this study, only an IV product was available. The SC formulation is now available containing the same daclizumab drug product. Preliminary studies indicate that the SC formulation is well tolerated by normal control subjects and other autoimmune disease patients at repeated doses up to 2 mg/kg.

The primary objectives are to examine the safety and potential efficacy of IV and later, SC daclizumab, while continuing to reduce other immunosuppressive medications commensurate with the standard of care. Primary safety outcomes are the discontinuation of study therapy due to reduced vision or the occurrence of adverse events. Secondary outcome measures include visual acuity and the grading of immunosuppressive medications, anterior chamber and vitreous cells, and vitreous haze.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA

Participant is 18 years of age or older.

Participant has a diagnosis of sight-threatening, intermediate or posterior uveitis of at least three months duration prior to orginal enrollment, requiring treatment to control their intraocular inflammatory disease with at least 20 mg/day of prednisone (or equivalent) or any combination of two or more anti-inflammatory treatments for uveitis, including for example prednisone, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, methotrexate, etc.

Participant exhibits intolerance to the indicated systemic medications required for their uveitis or, though their uveitis may be under control, wish to be taken off their present medications due to potential or actual unacceptable side effects.

Participant has visual acuity in at least one eye of 20/63 or better (ETDRS, logMAR less than 0.54).

Participant has normal renal or liver function or evidence of no worse than mild abnormalities as defined by the WHO/NEI criteria.

Participant is not currently pregnant or lactating.

Participant with reproductive potential and who is sexually active agrees to use acceptable birth control methods throughout the course of the study.

EXCLUSION CRITERIA

Participants under the age of 18 years.

Participants who had received previous treatment with an IL-2 directed monoclonal antibody or any other investigational agent that would interfere with the ability to evaluate the safety, efficacy or pharmacokinetics of daclizumab.

Participants with a history or diagnosis of Behcet's disease.

Participant has a significant active infection.

Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.

Participant is hypersensitive to fluorescein dye.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001526

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001526     History of Changes
Other Study ID Numbers: 960096, 96-EI-0096
Study First Received: November 3, 1999
Last Updated: September 7, 2007
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Uveitis
Interleukin 2 Receptor
Daclizumab
HAT
Zenapax
Interleukin 2

Additional relevant MeSH terms:
Uveitis
Chorioretinitis
Uveal Diseases
Eye Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis
Daclizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014