Optiquel® as Corticosteroid-sparing Therapy for Chronic Noninfectious Uveitis
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Uveitis
Intervention: B27PD (Drug); Placebo (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: National Eye Institute (NEI) Official(s) and/or principal investigator(s): Robert B Nussenblatt, M.D., Principal Investigator, Affiliation: National Eye Institute (NEI)
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.
Clinical Details
Official title: Peptide B27PD (Optiquel®) as Corticosteroid-sparing Therapy for Chronic Non-infectious Uveitis (BOOTS)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: 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) LettersProportion 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 Mean Change in Best-Corrected Visual Acuity (BCVA) in Right Eye (OD) at Week 24 Compared to Baseline Mean Change in Best-Corrected Visual Acuity (BCVA) in Left Eye (OS) at Week 24 Compared to Baseline Number of Participants Presenting No Change in Retinal Vessel Leakage Observed by Fluorescein Angiography (FA) at Week 24 Compared to Baseline Number of Participants Presenting No Change in Autofluorescence Patterns as Observed on Fundus Autofluorescence (FAF) at Week 24 Compared to Baseline Reduction in Exposure to Corticosteroid as Measured by the Area Under the Dose-time Curve. Changes in High-speed Indocyanine Green Angiography (HS-ICG)
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information
Related publications: Barnett ML, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DE. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 1998 Feb;41(2):290-7. Erratum in: Arthritis Rheum 1998 May;41(5):938. Dandona L, Dandona R, John RK, McCarty CA, Rao GN. Population based assessment of uveitis in an urban population in southern India. Br J Ophthalmol. 2000 Jul;84(7):706-9.
Starting date: August 2010
Last updated: December 1, 2014
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