UveitisPhase 1NCT00078689
Daclizumab and Sirolimus to Treat Uveitis
A Phase 1 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 whether the combination of the drugs daclizumab and sirolimus can effectively treat adults with uveitis, an eye inflammation. Daclizumab is a monoclonal antibody that is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. 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
- 3 Mar 2004to 18 Jul 2008
- Phase
- Phase 1
- 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
- Participant is 18 years of age or older.
- Participant with uveitis in one or both eyes on daclizumab monotherapy without disease flare in the past 6 months.
- Participant agrees to use acceptable birth control methods throughout the course of the study and for 6 months after completion of treatment with daclizumab or sirolimus.
- Participant is able to understand and sign a consent form before entering the study.
Who cannot join
- Participant with a history of hypersensitivity to FK506 or sirolimus.
- Participant who has had major surgery in the past 6 months.
- Participant is pregnant or lactating.
- Participant with active chronic or acute infections.
- Participant with malignancy other than squamous cell carcinoma in situ.
- Participant with uncontrolled hyperlipidemia at the time of enrollment.
Show all 9Show fewer
- Participant without VZV antibodies.
- Participant without Hepatitis antibodies (anti-HAV or anti-HBc) AND with any one of the following risk factors for acquiring hepatitis: IV drug abuse, male homosexual activity, hemophilia, prostitution, or health care work.
- Participant requiring systemic anti-fungal therapy with ketoconazole for whom no other acceptable alternative anti-fungal therapy exists.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Combination Daclizumab/Sirolimus Therapy For the Induction of Immune Tolerance in Non-Infectious Intermediate and Posterior Uveitis
This study will examine whether the combination of the drugs daclizumab and sirolimus can effectively treat adults with uveitis, an eye inflammation. Daclizumab is a monoclonal antibody that is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. Sirolimus is an immune-suppressing drug that also controls lymphocyte activity and is marketed to prevent organ rejection in kidney transplants.
Patients 18 years of age and older with non-infectious uveitis in one or both eyes who are being treated with daclizumab and have not had a relapse or disease flare for 6 months before entering this trial may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, complete eye examination, and pregnancy test for women who can have children. Women of child-bearing potential who enroll in this study will have a pregnancy test every 12 weeks.
Read more
After enrollment, participants have the following additional exams:
- Fluorescein angiography: This test is done to check for abnormalities of eye blood vessels. A yellow dye is injected into an arm vein and 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. This test is done at enrollment and after 1 year, unless additional tests are needed for medical management.
- Pelvic ultrasound and urine test: These tests are done at enrollment and after 1 year to check the kidneys, lymph nodes, and pelvic area.
- Blood tests: Blood tests are done at enrollment and every 3 to 6 months for laboratory and immunology study
Patients receive daclizumab subcutaneously (under the skin) or in infusions at regularly scheduled visits for 52 weeks. At each treatment, blood pressure, pulse, breathing rate, and temperature are monitored. After the first 52 weeks, patients whose disease remains quiet increase the time between injections to 6 weeks and then to 8 weeks. Patients who are doing well at this time may stop daclizumab.
One or 2 days after the first daclizumab treatment, patients receive 6 mg of sirolimus by mouth. Their blood pressure, pulse, breathing rate, and temperature are monitored for at least 60 minutes. Two days after the first dose, patients begin 2-mg maintenance doses every other day for 2 weeks. If there are no intolerable side effects, the dose is increased to 2 mg daily for the next 2 weeks. Patients who have no intolerable side effects at that dose continue the medication for another 4 weeks. Patients who experience intolerable side effects may decrease the medication to every other day or withdraw from the study. After week 78 of the study, if the daclizumab treatments are stopped, the sirolimus dose is reduced within 8 weeks and may eventually be discontinued if the patient continues to do well.
Patients who experience any of the following will leave the study:
- Inflammation flare that requires concomitant treatment with additional systemic immunosuppressive medications, such as prednisone or cyclosporine
- Disease flares more than twice in the first year
- Any disease flares in the second year
Read the detailed description
We propose to investigate the possible efficacy of combination daclizumab and sirolimus therapy to induce peripheral immune tolerance in participants presenting with non-infectious intermediate and posterior uveitis. This will be performed using a Phase I/II pilot study. Subjects on daclizumab monotherapy will receive a 6 mg loading dose of oral sirolimus at week 0, followed by a 2 mg dose every other day for 2 weeks. If tolerated, the subject will be increased to a 2 mg daily dose. After one year of combination therapy, the subject will be tapered off daclizumab first and then sirolimus. The primary outcome will be the ability of the participant to be successfully tapered off daclizumab and sirolimus while their disease remains quiet (vitreous haze less than or equal to Trace) for 24 weeks on no systemic immunosuppressive medications (approximately week 134).
- Conditions
- Uveitis
- Being tested
- Daclizumab
- Keywords
- Sirolimus, Daclizumab, Inflammation, Induce Tolerance, Uveitis, Immune Tolerance, T Cell
- Medical subject headings
- Uveitis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Ability to taper off drug while disease remains quiet at week 108 while receiving no concomitant systemic immunosuppressive medications.
Secondary outcomes (1)
Number and severity of disease flares requiring changes in concomitant immunosuppressive medication.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2004 (estimated)
- Study start3 Mar 2004
- Study completion18 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- 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
- NCT00078689
- Sponsor's protocol ID
- 040115
- Other IDs
- 04-EI-0115
- Status last verified
- 18 Jul 2008
- First submitted
- 4 Mar 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Caspi RR, Roberge FG, McAllister CG, el-Saied M, Kuwabara T, Gery I, Hanna E, Nussenblatt RB. T cell lines mediating experimental autoimmune uveoretinitis (EAU) in the rat. J Immunol. 1986 Feb 1;136(3):928-33.
PubMed 2416842Ramos EL, Leggat JE, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Carpenter CB. In vivo anti-interleukin-2 receptor (anti-Tac) therapy is immunosuppressive, but not tolerogenic. Trans Assoc Am Physicians. 1989;102:231-9. No abstract available.
PubMed 2534707Herve P, Wijdenes J, Bergerat JP, Bordigoni P, Milpied N, Cahn JY, Clement C, Beliard R, Morel-Fourrier B, Racadot E, et al. Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10). Blood. 1990 Feb 15;75(4):1017-23.
PubMed 2136244
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
- Combination Daclizumab/Sirolimus Therapy For the Induction of Immune Tolerance in Non-Infectious Intermediate and Posterior Uveitis
- ClinicalTrials.gov ID
- NCT00078689
- Acronym / sponsor ID
- 040115
- Conditions
- Uveitis
- Keywords
- Sirolimus, Daclizumab, Inflammation, Induce Tolerance, Uveitis, Immune Tolerance, T Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 3 Mar 2004
- Study completion
- 18 Jul 2008
- First posted
- 5 Mar 2004 (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 whether the combination of the drugs daclizumab and sirolimus can effectively treat adults with uveitis, an eye inflammation. Daclizumab is a monoclonal antibody that is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. Sirolimus is an immune-suppressing drug that also controls lymphocyte activity and is marketed to prevent organ rejection in kidney transplants.
Patients 18 years of age and older with non-infectious uveitis in one or both eyes who are being treated with daclizumab and have not had a relapse or disease flare for 6 months before entering this trial may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, complete eye examination, and pregnancy test for women who can have children. Women of child-bearing potential who enroll in this study will have a pregnancy test every 12 weeks.
After enrollment, participants have the following additional exams:
- Fluorescein angiography: This test is done to check for abnormalities of eye blood vessels. A yellow dye is injected into an arm vein and 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. This test is done at enrollment and after 1 year, unless additional tests are needed for medical management.
- Pelvic ultrasound and urine test: These tests are done at enrollment and after 1 year to check the kidneys, lymph nodes, and pelvic area.
- Blood tests: Blood tests are done at enrollment and every 3 to 6 months for laboratory and immunology study
Patients receive daclizumab subcutaneously (under the skin) or in infusions at regularly scheduled visits for 52 weeks. At each treatment, blood pressure, pulse, breathing rate, and temperature are monitored. After the first 52 weeks, patients whose disease remains quiet increase the time between injections to 6 weeks and then to 8 weeks. Patients who are doing well at this time may stop daclizumab.
One or 2 days after the first daclizumab treatment, patients receive 6 mg of sirolimus by mouth. Their blood pressure, pulse, breathing rate, and temperature are monitored for at least 60 minutes. Two days after the first dose, patients begin 2-mg maintenance doses every other day for 2 weeks. If there are no intolerable side effects, the dose is increased to 2 mg daily for the next 2 weeks. Patients who have no intolerable side effects at that dose continue the medication for another 4 weeks. Patients who experience intolerable side effects may decrease the medication to every other day or withdraw from the study. After week 78 of the study, if the daclizumab treatments are stopped, the sirolimus dose is reduced within 8 weeks and may eventually be discontinued if the patient continues to do well.
Patients who experience any of the following will leave the study:
- Inflammation flare that requires concomitant treatment with additional systemic immunosuppressive medications, such as prednisone or cyclosporine
- Disease flares more than twice in the first year
- Any disease flares in the second year
Detailed description
We propose to investigate the possible efficacy of combination daclizumab and sirolimus therapy to induce peripheral immune tolerance in participants presenting with non-infectious intermediate and posterior uveitis. This will be performed using a Phase I/II pilot study. Subjects on daclizumab monotherapy will receive a 6 mg loading dose of oral sirolimus at week 0, followed by a 2 mg dose every other day for 2 weeks. If tolerated, the subject will be increased to a 2 mg daily dose. After one year of combination therapy, the subject will be tapered off daclizumab first and then sirolimus. The primary outcome will be the ability of the participant to be successfully tapered off daclizumab and sirolimus while their disease remains quiet (vitreous haze less than or equal to Trace) for 24 weeks on no systemic immunosuppressive medications (approximately week 134).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participant is 18 years of age or older.
- Participant with uveitis in one or both eyes on daclizumab monotherapy without disease flare in the past 6 months.
- Participant agrees to use acceptable birth control methods throughout the course of the study and for 6 months after completion of treatment with daclizumab or sirolimus.
- Participant is able to understand and sign a consent form before entering the study.
Key exclusion criteria (9 listed)
- Participant with a history of hypersensitivity to FK506 or sirolimus.
- Participant who has had major surgery in the past 6 months.
- Participant is pregnant or lactating.
- Participant with active chronic or acute infections.
- Participant with malignancy other than squamous cell carcinoma in situ.
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
Ability to taper off drug while disease remains quiet at week 108 while receiving no concomitant systemic immunosuppressive medications.
1 secondary outcome
Number and severity of disease flares requiring changes in concomitant immunosuppressive medication.
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 2416842Caspi RR, Roberge FG, McAllister CG, el-Saied M, Kuwabara T, Gery I, Hanna E, Nussenblatt RB. T cell lines mediating experimental autoimmune uveoretinitis (EAU) in the rat. J Immunol. 1986 Feb 1;136(3):928-33.
- Background: PubMed 2534707Ramos EL, Leggat JE, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Carpenter CB. In vivo anti-interleukin-2 receptor (anti-Tac) therapy is immunosuppressive, but not tolerogenic. Trans Assoc Am Physicians. 1989;102:231-9. No abstract available.
- Background: PubMed 2136244Herve P, Wijdenes J, Bergerat JP, Bordigoni P, Milpied N, Cahn JY, Clement C, Beliard R, Morel-Fourrier B, Racadot E, et al. Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10). Blood. 1990 Feb 15;75(4):1017-23.
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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 1 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 4 inclusion and 9 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
What does the primary outcome measure?
Ability to taper off drug while disease remains quiet at week 108 while receiving no concomitant systemic immunosuppressive medications.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00078689, which also lists 3 linked publications.
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.