UveitisPhase 2NCT00070759
Daclizumab to Treat Non-Infectious Sight-Threatening Uveitis
A Phase 2 study testing Daclizumab in people with Uveitis, run by National Eye Institute (NEI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveitis
- What is being tested?
- Daclizumab
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2003to 2 Oct 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Volunteers will be considered eligible participants for this study provided they meet all of the following inclusion criteria:
- Participant has a diagnosis of active, non-infectious intermediate or posterior uveitis, which may include but is not restricted to the following conditions known to cause intermediate or posterior uveitis: panuveitis, intermediate uveitis of the pars planitis subtype, sarcoidosis, the Vogt-Koyanagi-Harada (VKH) syndrome, birdshot retinochoroidopathy, retinal vasculitis and sympathetic ophthalmia;
- Participant has active uveitis with greater than or equal to Grade 1 (1+) vitreous haze in at least one eye including evidence of retinal vascular leakage using fluorescein angiography or the presence of cystoid macular edema (CME) at enrollment;
- Participant's uveitis is currently treated or untreated at the time of enrollment;
- Participant has best-corrected distance visual acuity (BCVA) in the worst eye of 20/400 or better (ETDRS logMAR less than 1.34);
- Participant does not plan to undergo elective ocular surgery (e.g., cataract extraction) during the study period;
- Participant, male or female, with reproductive potential and who is sexually active agrees to use double-barrier contraception methods throughout the course of the study (minimum of 52 weeks) and for 6 additional weeks after completion of the protocol treatment period.
Who cannot join
- A volunteer will not be permitted to enroll if they meet any one of the following exclusion criteria:
- Participant is under 18 years of age;
- Participant has received previous treatment with an IL-2 or IL-2R directed therapy within the past 90 days;
- Participant has lens opacities or obscured anterior ocular media upon enrollment such that reliable evaluation and grading of posterior segment cannot be performed (except that anterior chamber cells due to inflammation is not an exclusion);
- Participant has a history of an active herpes zoster or varicella infection within 6 weeks before enrollment, or chicken pox exposure within 21 days before enrollment.
- Participant has a known history of HIV infection;
Show all 12Show fewer
- Participant is currently enrolled in another investigational or interventional therapeutic trial, or is using a therapy for a non-uveitis condition that would likely affect immune responses or interfere with trial logistics, or has received any investigational therapy within the 30 days prior to enrollment;
- Participant has a history or diagnosis of Behcet's disease (since subsequent tapering or withdrawal of concomitant immunosuppressive medications is not a standard-of-care for Behcet's patients) or a primary diagnosis of anterior uveitis (e.g., HLA-B27 associated uveitis, or ocular conditions usually treated with local and not systemic medications);
- Participant has a significant local or systemic infection requiring medical treatment at the time of enrollment;
- Participant is currently pregnant or lactating;
- Participant has a history of cancer (other than a non-melanoma skin cancer or in situ cervical cancer) diagnosed within the past 5 years;
- Participant has a non-ocular, medically significant co-morbid condition that impairs normal activities, requires immunosuppression, or has a condition with a prognosis that indicates a significant risk of disability or death if the condition were to continue or be exacerbated during the study period, or a medical condition that would likely have an impact on the participant's ability to comply with the visit schedule. Such conditions may include, for example, recent heart attack, significant COPD, brittle diabetes, kidney disease, severe emphysema, organ transplant (requiring corticosteroids or other immunosuppressive medications), hepatitis or other liver disease, or uncontrolled psychiatric illnesses.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Eye Institute (NEI)
Bethesda, Maryland, 20892
About this study
Official title: Daclizumab for Active, Non-infectious, Sight-threatening Uveitis: A Phase II Pilot Study
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:
Read more
- 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.
Read the 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.
- Conditions
- Uveitis
- Being tested
- Daclizumab
- Keywords
- Daclizumab, Uveitis, Active, Acute
- Medical subject headings
- Uveitis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2003 (estimated)
- Study start6 Oct 2003
- Study completion2 Oct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for UveitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 6 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00070759
- Sponsor's protocol ID
- 040006
- Other IDs
- 04-EI-0006
- Status last verified
- 2 Oct 2006
- First submitted
- 7 Oct 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Lacomba MS, Martin CM, Chamond RR, Galera JM, Omar M, Estevez EC. Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol. 2000 Jun;118(6):768-72. doi: 10.1001/archopht.118.6.768.
PubMed 10865312
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daclizumab for Active, Non-infectious, Sight-threatening Uveitis: A Phase II Pilot Study
- ClinicalTrials.gov ID
- NCT00070759
- Acronym / sponsor ID
- 040006
- Conditions
- Uveitis
- Keywords
- Daclizumab, Uveitis, Active, Acute
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 6 Oct 2003
- Study completion
- 2 Oct 2006
- First posted
- 8 Oct 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Volunteers will be considered eligible participants for this study provided they meet all of the following inclusion criteria:
- Participant has a diagnosis of active, non-infectious intermediate or posterior uveitis, which may include but is not restricted to the following conditions known to cause intermediate or posterior uveitis: panuveitis, intermediate uveitis of the pars planitis subtype, sarcoidosis, the Vogt-Koyanagi-Harada (VKH) syndrome, birdshot retinochoroidopathy, retinal vasculitis and sympathetic ophthalmia;
- Participant has active uveitis with greater than or equal to Grade 1 (1+) vitreous haze in at least one eye including evidence of retinal vascular leakage using fluorescein angiography or the presence of cystoid macular edema (CME) at enrollment;
- Participant's uveitis is currently treated or untreated at the time of enrollment;
- Participant has best-corrected distance visual acuity (BCVA) in the worst eye of 20/400 or better (ETDRS logMAR less than 1.34);
Key exclusion criteria (12 listed)
- A volunteer will not be permitted to enroll if they meet any one of the following exclusion criteria:
- Participant is under 18 years of age;
- Participant has received previous treatment with an IL-2 or IL-2R directed therapy within the past 90 days;
- Participant has lens opacities or obscured anterior ocular media upon enrollment such that reliable evaluation and grading of posterior segment cannot be performed (except that anterior chamber cells due to inflammation is not an exclusion);
- Participant has a history of an active herpes zoster or varicella infection within 6 weeks before enrollment, or chicken pox exposure within 21 days before enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daclizumab | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10865312Lacomba MS, Martin CM, Chamond RR, Galera JM, Omar M, Estevez EC. Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol. 2000 Jun;118(6):768-72. doi: 10.1001/archopht.118.6.768.
Related trials for Uveitis
RecruitingPhase 3
A Study of Apremilast in Children With Oral Ulcers Associated With Behçet's Disease or Juvenile Psoriatic Arthritis
Behçet's Disease, Juvenile Psoriatic Arthritis
Not yet recruiting
Efficacy and Safety of Adalimumab for the Treatment of Ocular Inflammation
Non-infectious Anterior Uveitis, Non-infectious Intermediate Uveitis
RecruitingObservational study
A Study of Uveitis in Children <18 Years of Age
Uveitis
Active, not recruitingPhase 2
Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Uveitis Related and Post Surgical Macular Edema
Uveitis Related Cystoid Macular Edema, Cystoid Macular Edema, Postoperative
RecruitingPhase 1
A Proof-of-concept Trial to EvaluAte the efficaCy and Safety Of Cell Therapy TRX103 in Patients With Active, Non-infectious Uveitis
Non Infectious Uveitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daclizumab in people with Uveitis, run by National Eye Institute (NEI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00070759, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.