Non-infectious Intermediate and Posterior UveitisPhase 2NCT00326508
Combination Daclizumab/Denileukin Diftitox to Treat Uveitis
A Phase 2 study testing Daclizumab in people with Non-infectious Intermediate and Posterior Uveitis, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will determine whether treatment with a combination of the drugs daclizumab and denileukin diftitox can eliminate the need for long-term daclizumab treatment in adult patients with uveitis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-infectious Intermediate and Posterior Uveitis
- What is being tested?
- Daclizumab
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2006to 20 Dec 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible to enroll in this study, a prospective participant must satisfy the following inclusion criteria.
- Participant is 18 years of age or older. (The vast majority of T cells are produced before adulthood and the long-term consequences of inducing immune tolerance are unknown, it would thus seem prudent to exclude juveniles from the study.)
- Participant with uveitis in one or both eyes on daclizumab therapy without disease flare in the past 6 months.
- Participants of reproductive age agree 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 must be willing and prepared to travel to NIH on short notice for treatment and to be hospitalized if deemed medically necessary.
- Participant is able to understand and sign a consent form before entering the study.
Who cannot join
- To be eligible to enroll in this study, a prospective participant must not satisfy any of the following exclusion criteria.
- Participant with a history of hypersensitivity to denileukin diftitox.
- Participant is pregnant or lactating.
- Participant with active chronic or acute infections.
- Participant with a history of cardiovascular disease, significant respiratory disease, coagulation disorders, or other major medical illnesses that may limit their ability to tolerate the toxicities associated with denileukin diftitox.
- Participant with a serum albumin less than 3.0.
- Participant with malignancy other than squamous cell carcinoma in situ.
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/Denileukin Diftitox (Ontak) Therapy for the Induction of Immune Tolerance in Non-infectious Intermediate and Posterior Uveitis
This study will determine whether treatment with a combination of the drugs daclizumab and denileukin diftitox can eliminate the need for long-term daclizumab treatment in adult patients with uveitis. Denileukin diftitox kills white blood cells called lymphocytes that cause inflammation and may be the cause of uveitis.
Patients 18 years of age and older with uveitis in one or both eyes who are on daclizumab therapy and have not had a disease flareup in 6 months may be eligible for this study. Candidates are screened with a medical history, physical examination, eye examination (including vision test, examination of the front of the eye, and pupil dilation for examination of the retina at the back of the eye), blood tests and a questionnaire about their vision and daily activities.
Read more
After screening, participants undergo the following procedures:
- Daclizumab/ denileukin diftitox treatment. Patients receive their regular dose of daclizumab intravenously (through a vein). The interval between doses is increased by 1 week after each dose. When the doses are 10 weeks apart, the daclizumab is stopped. Patients who experience a flare or uveitis are treated with intravenous denileukin diftitox and possibly local injections of steroids around the eye or increasing or adding other medicines as needed to control the uveitis.
- Fluorescein angiography to look for blood vessel abnormalities in the eyes. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) 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.
- Ultrasound and urine tests at enrollment and after 1 year to check kidneys, lymph nodes and pelvic area.
- Blood tests at enrollment and every 3-6 months for laboratory and immunology tests and other research tests on blood cells to examine the immune response.
- Follow-up visits approximately every 6 weeks for 2 years for repeat examinations to determine the response to treatment and drug side effects.
Read the detailed description
We propose to investigate the possible efficacy of combination daclizumab and denileukin diftitox 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 whose disease is controlled on daclizumab therapy will have their daclizumab-dosing interval progressively increased by one-week increments. If and when they experience signs or symptoms of an ocular flare, they will be treated with denileukin diftitox, 24 hours after which they will receive their usual dose of daclizumab. Participants may receive up to 12 such cycles of daclizumab/denileukin diftitox therapy. When the daclizumab-dosing interval is 10 weeks long or less than 10% of their CD4 T cell CD25 is occupied by daclizumab, therapy will be discontinued. Following discontinuation of daclizumab patients will be followed for recurrence of ocular disease. Failure to reach this study point after 12 cycles or disease recurrence following discontinuation of therapy will constitute a study failure. The primary outcome will be the ability of the participant to be successfully tapered off daclizumab while their disease remains quiet (vitreous haze less than or equal to Trace) at week 104 while receiving no concomitant systemic immunosuppressive medications.
- Being tested
- Daclizumab
- Keywords
- T Lymphocytes, IL-2 Conjugate, CD25, T Regulatory Cells, Autoimmunity, Uveitis, Daclizumab, Denileukin Diftitox, Immune Tolerance, T Cell
- Medical subject headings
- Uveitis, Posterior, Autoimmune Diseases, Uveitis
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 posted17 May 2006 (estimated)
- Study start11 May 2006
- Study completion20 Dec 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 Non-infectious Intermediate and Posterior 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
- 5 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00326508
- Sponsor's protocol ID
- 060066
- Other IDs
- 06-EI-0066
- Status last verified
- 20 Dec 2006
- First submitted
- 16 May 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Herve 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/Denileukin Diftitox (Ontak) Therapy for the Induction of Immune Tolerance in Non-infectious Intermediate and Posterior Uveitis
- ClinicalTrials.gov ID
- NCT00326508
- Acronym / sponsor ID
- 060066
- Keywords
- T Lymphocytes, IL-2 Conjugate, CD25, T Regulatory Cells, Autoimmunity, Uveitis, Daclizumab, Denileukin Diftitox
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 11 May 2006
- Study completion
- 20 Dec 2006
- First posted
- 17 May 2006 (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 determine whether treatment with a combination of the drugs daclizumab and denileukin diftitox can eliminate the need for long-term daclizumab treatment in adult patients with uveitis. Denileukin diftitox kills white blood cells called lymphocytes that cause inflammation and may be the cause of uveitis.
Patients 18 years of age and older with uveitis in one or both eyes who are on daclizumab therapy and have not had a disease flareup in 6 months may be eligible for this study. Candidates are screened with a medical history, physical examination, eye examination (including vision test, examination of the front of the eye, and pupil dilation for examination of the retina at the back of the eye), blood tests and a questionnaire about their vision and daily activities.
After screening, participants undergo the following procedures:
- Daclizumab/ denileukin diftitox treatment. Patients receive their regular dose of daclizumab intravenously (through a vein). The interval between doses is increased by 1 week after each dose. When the doses are 10 weeks apart, the daclizumab is stopped. Patients who experience a flare or uveitis are treated with intravenous denileukin diftitox and possibly local injections of steroids around the eye or increasing or adding other medicines as needed to control the uveitis.
- Fluorescein angiography to look for blood vessel abnormalities in the eyes. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) 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.
- Ultrasound and urine tests at enrollment and after 1 year to check kidneys, lymph nodes and pelvic area.
- Blood tests at enrollment and every 3-6 months for laboratory and immunology tests and other research tests on blood cells to examine the immune response.
- Follow-up visits approximately every 6 weeks for 2 years for repeat examinations to determine the response to treatment and drug side effects.
Detailed description
We propose to investigate the possible efficacy of combination daclizumab and denileukin diftitox 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 whose disease is controlled on daclizumab therapy will have their daclizumab-dosing interval progressively increased by one-week increments. If and when they experience signs or symptoms of an ocular flare, they will be treated with denileukin diftitox, 24 hours after which they will receive their usual dose of daclizumab. Participants may receive up to 12 such cycles of daclizumab/denileukin diftitox therapy. When the daclizumab-dosing interval is 10 weeks long or less than 10% of their CD4 T cell CD25 is occupied by daclizumab, therapy will be discontinued. Following discontinuation of daclizumab patients will be followed for recurrence of ocular disease. Failure to reach this study point after 12 cycles or disease recurrence following discontinuation of therapy will constitute a study failure. The primary outcome will be the ability of the participant to be successfully tapered off daclizumab while their disease remains quiet (vitreous haze less than or equal to Trace) at week 104 while receiving no concomitant systemic immunosuppressive medications.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- To be eligible to enroll in this study, a prospective participant must satisfy the following inclusion criteria.
- Participant is 18 years of age or older. (The vast majority of T cells are produced before adulthood and the long-term consequences of inducing immune tolerance are unknown, it would thus seem prudent to exclude juveniles from the study.)
- Participant with uveitis in one or both eyes on daclizumab therapy without disease flare in the past 6 months.
- Participants of reproductive age agree 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 must be willing and prepared to travel to NIH on short notice for treatment and to be hospitalized if deemed medically necessary.
Key exclusion criteria (7 listed)
- To be eligible to enroll in this study, a prospective participant must not satisfy any of the following exclusion criteria.
- Participant with a history of hypersensitivity to denileukin diftitox.
- Participant is pregnant or lactating.
- Participant with active chronic or acute infections.
- Participant with a history of cardiovascular disease, significant respiratory disease, coagulation disorders, or other major medical illnesses that may limit their ability to tolerate the toxicities associated with denileukin diftitox.
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 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 2 study testing Daclizumab in people with Non-infectious Intermediate and Posterior 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 6 inclusion and 7 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 NCT00326508, 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.