Clinical trial NCT01195948: Optiquel® as Corticosteroid-sparing Therapy for Chronic Noninfectious Uveitis
Official title: Peptide B27PD (Optiquel®) as Corticosteroid-sparing Therapy for Chronic Non-infectious Uveitis (BOOTS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Uveitis
Keywords: Uveitis
Oral Tolerance
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: The Emmes Company, LLC
First posted: 2010-09-06
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background:

Uveitis is a serious inflammatory condition in which the body's immune system attacks parts of the eye, often causing vision loss. Uveitis treatments involve various drugs that suppress the immune system, but these medicines sometimes do not work or may cause serious side effects. Researchers are interested in developing new treatments for uveitis that are more effective and have fewer side effects.

Optiquel® is an experimental medication being tested for its effectiveness against uveitis. It contains B27PD, a small protein fragment, which is similar to proteins in the parts of the eye being attacked by the immune system. Taking Optiquel® (B27PD) by mouth may induce oral tolerance, in which the immune system is taught to recognize and not attack normal parts of the human body.

Objectives:

To evaluate the safety and effectiveness of B27PD (Optiquel®) as a treatment for uveitis.

Eligibility:

Individuals at least 18 years of age who have had noninfectious uveitis in one or both eyes for at least 3 months, have vision of 20/200 or better in at least one eye, and are taking daily prednisone or an equivalent medication.

Design:

Participants will be screened with a physical examination, medical history, blood and urine tests, and an eye exam.

This study will last a maximum of 52 weeks. During the first 12 weeks of the study, participants will have a study visit every 2 weeks. For the remainder of the study, participants will have a study visit every 4 weeks.

Participants will have frequent blood and urine tests, and will also have eye examinations and special procedures (fluorescein angiography and indocyanine green angiography) to evaluate the effectiveness of the treatment.

Participants will be randomly assigned into one of three groups and will receive either one of two different doses of B27PD or a placebo. During the study, participants will also have their dose of prednisone or other steroid medication reduced.

Participants will take one capsule three times per week on Monday, Wednesday, and Friday, for a total of 24 weeks. Participants may take the capsule with water, but should not consume any other drinks or any kind of food until at least 30 minutes have passed to prevent stomach upset. The capsules should be stored in the refrigerator.

Detailed description: Objective: The objective of this study is to evaluate the safety and efficacy of the peptide B27PD (Optiquel®) as a corticosteroid-sparing agent for chronic non-infectious uveitis in participants receiving oral corticosteroid therapy alone or combined with an immunosuppressive agent in a proof-of-concept clinical trial.

Study Population: Patients with non-infectious uveitis requiring at least 20 mg but no more than 40 mg of oral prednisone, or equipotent dose of alternative corticosteroid medication to maintain a quiescent eye, will be eligible.

Design: In this single center, Phase I/II, double-masked, randomized, placebo-controlled, parallel group treatment study, the safety and efficacy of the peptide B27PD will be investigated in 60 participants with non-infectious uveitis. Initially, 60 participants were to be enrolled; however, due to lack of efficacy, only 31 participants were enrolled. Eligible participants will be randomized to one of three treatment groups: 1 mg B27PD, 4 mg B27PD or placebo, to be taken three times per week for 24 weeks. All remaining participants will be followed through a common termination date. The common termination date will be established once the last enrolled participant reaches his/her Week 28 visit (four weeks following his/her last investigational treatment).The time to recurrence of uveitis in either eye occurring in the 52 weeks following the initial dosing will be evaluated in each treatment group. Recurrence will be defined as an increase in anterior chamber cells and/or vitreous haze of at least 2 steps \[using the Standardization of Uveitis Nomenclature (SUN) grading system\]. Ophthalmic examinations to assess uveitis will include visual acuity, intraocular pressure (IOP), slit lamp biomicroscopy, ophthalmoscopy, optical coherence tomography (OCT) and fluorescein angiography.

Outcome Measures: The primary outcome variable is the time to recurrence of uveitis activity in participants of each treatment group, during or after tapering of oral prednisone to a dose of 7.5 mg/day, or equipotent dose of alternative corticosteroid medication. Secondary efficacy outcome variables include the proportion of participants determined to be a Treatment Failure, defined as recurrence (or flare) of uveitis (at least a 2-step increase using the SUN grading system) or a drop in visual acuity of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 24 and 52 weeks. Other secondary efficacy outcomes include the reduction in exposure to corticosteroid as measured by the area under the dose-time curve, and changes in best-corrected visual acuity (BCVA), fluorescein angiography, fundus autofluorescence and high-speed indocyanine green angiography (HS-ICG). Ocular safety measurements include intraocular pressure (IOP) and optical coherence tomography (OCT) for confirmation of suspected macular edema. Systemic safety variables include adverse events, clinical blood chemistry and hematology, urinalysis, vital signs, weight and medical evaluation at baseline and at the end of the study.

Eligibility criteria: INCLUSION CRITERIA:

* Participant must be 18 years of age or older.
* Participant must be able to understand the informed consent process and sign the informed consent form.
* Participant has been diagnosed with non-infectious unilateral or bilateral uveitis for at least three months. Participants who were diagnosed more than a year prior to enrollment must have had a recurrence in ocular inflammation within the past year.
* Participant must be receiving a current treatment with prednisone between 20 to 40 mg/day (or an equipotent dose of an alternative corticosteroid). Participants who are on a regimen of no more than one anti-metabolite inhibitor at the time of randomization (e.g., azathioprine, methotrexate, mycophenolate) in addition to the prednisone may be enrolled and are allowed to continue the anti-metabolite.
* The participant's uveitis must be controlled in eligible eyes, quiescent eyes \[anterior chamber cells and vitreous haze Standardization of Uveitis Nomenclature (SUN) grade of 0\].
* The participant's eligible eye(s) is able to be evaluated for activity of disease both biomicroscopically and ophthalmoscopically.
* The participant's baseline intraocular pressure must be \> 5 mmHg and ≤ to 30 mmHg in both eyes. Concurrent use of intraocular pressure-lowering medication and/or prior glaucoma surgery is acceptable.
* Participant has best-corrected distance visual acuity in the better seeing eye of 20/200 or better \[≥ 34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters\].
* Female participants of childbearing potential must not be pregnant or lactating and must be willing to undergo serum pregnancy tests throughout the study.
* Women of childbearing potential must agree to use reliable methods of contraception while receiving the study medication and for 6 weeks following the last administration. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or partner with vasectomy).

EXCLUSION CRITERIA:

* Participant has a non-iatrogenic immunodeficiency state \[e.g., Human Immunodeficiency Virus (HIV) infection or congenital immunodeficiency\].
* Participant had intraocular surgery or intraocular injection within three months prior to randomization.
* Participant is expected to have an elective ocular surgery or intraocular injection during the study period.
* Participant is using systemic corticosteroid therapy for a non-ocular disease or non-ocular organ involvement.
* Participant has a history or diagnosis of Behcet's disease.
* Participant has a clinically suspected and/or confirmed central nervous system or ocular lymphoma.
* Participant has an active systemic infectious disease or malignancy that requires treatment.
* Participant has a known chronic disease or condition of the gastrointestinal system that may interfere wih the absorption of the investigational product as determined by the investigator (e.g., active hepatitis, chronic diarrhea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, celiac disease, diverticulosis or diverticulitis).
* Participant has two or more food allergies.
* Participant has an implant containing anti-inflammatory, immunosuppressive or antiviral drugs, unless a period 50% longer than the anticipated duration of effect of the implant has elapsed.
* Participant received periocular corticosteroid injections within 4 months prior to randomization or is expected to need periocular corticosteroid injections during the study duration.
* Participant received treatment with infliximab, etanercept, adalimumab, interferon, cyclosporine, tacrolimus, sirolimus, within two weeks prior to randomization.
* Participant received cytotoxic therapy (e.g., cyclophosphamide) within six months prior to randomization.
* Participants for whom, in the physician's opinion, any of the protocol procedures may pose a special risk not outweighed by the potential benefits of participating in the study.
* Participant who is unlikely to comply with the study protocol or who is likely to be moving or lost to follow-up.
* Participant who is currently enrolled or has been participating in any other investigative therapeutic clinical trial during the three months prior to randomization.
* Participant has a known need for a colonoscopy or surgery of the gastrointestinal tract during the study.

Primary outcomes:
measure: The Primary Outcome is the Time to Recurrence of Uveitis in Participants of Each Treatment Group, During or After Tapering of Oral Prednisone to a Dose of 7.5 mg/Day, or Equipotent Dose of Alternative Corticosteroid Medication.
timeFrame: Time from randomization to recurrence, loss to follow-up, or end of study, up to 52 weeks
Secondary outcomes:
measure: Proportion of Participants Determined to be a Treatment Failure, Defined as Recurrent (or Flare) of Uveitis or a Drop in Visual Acuity of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters
timeFrame: Week 24
measure: Proportion of Participants Determined to be a Treatment Failure, Defined as Recurrent (or Flare) of Uveitis or a Drop in Visual Acuity of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters
timeFrame: Week 52
measure: Mean Change in Best-Corrected Visual Acuity (BCVA) in Right Eye (OD) at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Mean Change in Best-Corrected Visual Acuity (BCVA) in Left Eye (OS) at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Number of Participants Presenting No Change in Retinal Vessel Leakage Observed by Fluorescein Angiography (FA) at Week 24 Compared to Baseline
timeFrame: Week 24
measure: Number of Participants Presenting No Change in Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) at Week 24 Compared to Baseline
timeFrame: Week 24
measure: Reduction in Exposure to Corticosteroid as Measured by the Area Under the Dose-time Curve.
timeFrame: Week 24
measure: Changes in High-speed Indocyanine Green Angiography (HS-ICG)
timeFrame: Week 24
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Eye Institute (NEI)
name: Robert B Nussenblatt, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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