Optiquel® as Corticosteroid-sparing Therapy for Chronic Noninfectious Uveitis

NCT01195948 | Completed Phase 1 Results DMC

• 2 other identifiers: 10019110-EI-0191
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Uveitis

Keywords

Uveitis; Oral Tolerance

Outcome Measures

Primary Outcomes (1)

• 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.

  Recurrence (or flare) is defined as an anterior chamber cells and/or vitreous haze grading of ≥ 2+ using the Standardization of Uveitis Nomenclature (SUN) grading system. The time to this event is defined as the time from randomization to recurrence, loss to follow-up or end of study, whichever comes first. Participants that do not present with disease recurrence will be censored at the time of the last disease evaluation.

  Time from randomization to recurrence, loss to follow-up, or end of study, up to 52 weeks

Secondary Outcomes (8)

• 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

  Week 24

• 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

  Week 52

• Mean Change in Best-Corrected Visual Acuity (BCVA) in Right Eye (OD) at Week 24 Compared to Baseline

  Baseline and Week 24

• Mean Change in Best-Corrected Visual Acuity (BCVA) in Left Eye (OS) at Week 24 Compared to Baseline

  Baseline and Week 24

• Number of Participants Presenting No Change in Retinal Vessel Leakage Observed by Fluorescein Angiography (FA) at Week 24 Compared to Baseline

  Week 24

Study Arms (3)

B27PD 1 mg

EXPERIMENTAL

Participants randomly assigned to the B27PD 1 mg arm were instructed to take the capsule orally three times per week (i.e., Monday, Wednesday and Friday) in the morning, at least four hours after the last meal and at least 30 minutes before the next meal for 24 weeks.

Drug: B27PD

B27PD 4 mg

EXPERIMENTAL

Participants randomly assigned to the B27PD 4 mg arm were instructed to take the capsule orally three times per week (i.e., Monday, Wednesday and Friday) in the morning, at least four hours after the last meal and at least 30 minutes before the next meal for 24 weeks.

Drug: B27PD

Placebo

PLACEBO COMPARATOR

Participants randomly assigned to the placebo arm were instructed to take the capsule orally three times per week (i.e., Monday, Wednesday and Friday) in the morning, at least four hours after the last meal and at least 30 minutes before the next meal for 24 weeks.

Drug: Placebo

Interventions

B27PD DRUG

Also known as: Optiquel®

B27PD 1 mg; B27PD 4 mg

Placebo DRUG

Capsule with no active ingredients to mimic B27PD

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1002/1529-0131(199802)41:23.0.CO;2-R.

  PMID: 9485087 BACKGROUND

• 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. doi: 10.1136/bjo.84.7.706.

  PMID: 10873978 BACKGROUND

• Levy RA, de Andrade FA, Foeldvari I. Cutting-edge issues in autoimmune uveitis. Clin Rev Allergy Immunol. 2011 Oct;41(2):214-23. doi: 10.1007/s12016-011-8267-x.

  PMID: 21913066 DERIVED

MeSH Terms

Conditions

Uveitis

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Limitations and Caveats

The protocol was completed early due to lack of efficacy. The Data Safety Monitoring Committee (DSMC), along with the PI, reviewed an interim data report and agreed that Optiquel® was not efficacious and did not cause a proliferative response.

Results Point of Contact

• Title: Robert Nussenblatt, MD, MPH
• Organization: National Institutes of Health

robert.nussenblatt@nih.gov

301-496-3123

Study Officials

• Robert B Nussenblatt, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 6, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: February 1, 2014
• Last Updated: September 11, 2018
• Results First Posted: December 5, 2014

Record last verified: 2014-12

Locations

US (1)