Sirolimus Injections for Autoimmune Scleritis

NCT01517074 | Completed Phase 1 Results

• 2 other identifiers: 12005712-EI-0057
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Autoimmune scleritis is an inflammatory disease that affects the white outer part of the eye. It is associated with immune system disorders like rheumatoid arthritis. It can cause blindness in severe cases. Most treatments for scleritis involve steroid or immune-suppressing drugs, but these can cause side effects in the whole body. Sirolimus is a drug used to help prevent transplant rejection. It helps prevent the immune system from attacking the body. Researchers want to try giving sirolimus injections into the eye to treat severe scleritis. Objectives: To see if sirolimus is a safe and effective treatment for autoimmune scleritis. Eligibility: Individuals at least 18 years of age with autoimmune scleritis in at least one eye that has not responded to standard treatments. Design:

• Participants will be screened with a medical history, physical exam, and eye exam. Blood and urine samples will also be collected.
• One eye will be selected as the study eye to receive injections.
• Participants will have six study visits over 4 months (initial visit and weeks 2, 4, 8, 12, and 16). The injection will be given at the first visit. If the study eye responds to the treatment, participants may have injections in the other eye at the second visit.
• If there is still inflammation after the first injection, or if the scleritis improves but then returns, participants may have a second injection at Week 4.
• Injections will be monitored with blood tests and eye exams.
• Participants may have study visits and injections for up to 1 year if the injections seem to be working.

Conditions

Scleritis

Keywords

Sirolimus; Scleritis; Autoimmune Scleritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experience at Least 2-step Reduction or Reduction to Grade 0 of Scleral Inflammation in the Study Eye According to the National Eye Institute (NEI) Photographic Scleritis Grading System Within 8 Weeks Post-injection.

  The primary efficacy outcome was a 2-step reduction in scleritis grading out of a scale of 0 to 4+ (where 0.5+ is recognized as an ordinal step between 1+ and 0+). Scleral inflammation was graded following 10% Phenylephrine application with an ordinal scale of 0 (no scleral inflammation with complete blanching of vessels), 0.5+ (minimal/trace inflammation with localized pink appearance of the sclera around minimally dilated deep episcleral vessels), 1+ (mild inflammation with diffuse pink appearance of the sclera around mildly dilated deep episcleral vessels), 2+ (moderate inflammation with purplish pink appearance of the sclera with tortuous and engorged deep episcleral vessels), 3+ (severe inflammation with diffuse significant redness of sclera, the details of superficial and deep episcleral vessels can't be observed), and 4+ (necrotizing inflammation with diffuse redness of the sclera with scleral thinning and uveal show).

  Baseline and Week 8

Secondary Outcomes (11)

• Number of Participants Who Experience a Disease Flare as Defined by a ≥ 1-step Increase in Scleral Inflammation

  Baseline and Week 52

• Mean Change in Visual Acuity Via the Early Treatment Diabetic Retinopathy Study (ETDRS)

  Baseline and Week 52

• Median Change in Visual Acuity Via the Early Treatment Diabetic Retinopathy Study (ETDRS)

  Baseline and Week 52

• Number of Participants Needing a Second Injection

  Baseline and Week 52

• Mean Number of Days Between the First Injection to the Second Injection

  Baseline and Week 52

Study Arms (1)

Sirolimus

EXPERIMENTAL

Participants will receive a15 μL (660 μg) subconjunctival injection of sirolimus in the study eye at baseline if a single quadrant or two adjacent quadrants are involved. If greater than two quadrants are involved (i.e., 3 or 4 quadrant involvement) or two non-adjacent quadrants are involved, two 15 μL (660 μg) injections will be given in two quadrants 180 degrees apart (total dose of 30 μL or 1,320 μg). Participants that still demonstrate active inflammation (incomplete or no response to initial injection) or experience a flare-up (as defined by a ≥1-step increase in scleral inflammation) after the initial injection will be eligible for a re-injection in the study eye at or after Week 4 (not to exceed a dose of 1,320 μg per eye within an eight-week period).

Drug: Sirolimus

Interventions

Sirolimus DRUG

Subconjunctival injection

Also known as: Rapamune®, rapamycin

Sirolimus

Eligibility Criteria

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

You may qualify if:

• Participant has the ability to understand and sign the informed consent document.
• Participant is 18 years of age or older.
• Participant has a diagnosis of active, autoimmune, non-necrotizing, anterior scleritis.
• Participant, if currently taking immunosuppressive medications, is on a stable regimen of immunosuppressive medications (no increase and/or start of new immunosuppressive medications) over the last four weeks.
• Participant has tried therapy such as oral non-steroidal anti-inflammatory drugs (NSAIDs), or oral or topical corticosteroids or immunosuppressive medication at any time in the past to control scleritis flares, or has intolerance or contraindications to these medications.
• Participant is willing and able to comply with the study procedures.
• Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy tests throughout the study.
• Both female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for four months after the last investigational product injection. Acceptable methods of contraception include: hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation).

You may not qualify if:

• Participant has a significant active intraocular infection in either eye that requires antibiotic treatment.
• Participant has an active serious infection or a history of recurring serious infections such as human immunodeficiency virus (HIV) or syphilis that in the best medical judgment of the investigators would pose unnecessary risk to the participant.
• Participant has active joint or systemic inflammation requiring immediate addition or increase in systemic anti-inflammatory medications.
• Participant is taking systemic azole anti-fungal medication (e.g., ketoconazole, voriconazole, itraconazole).
• STUDY EYE ELIGIBILITY CRITERIA:
• Participant has anterior scleritis with greater than or equal to 1 plus in at least one quadrant of the study eye.
• Participant has visual acuity in the study eye of 20/640 or better.
• Participant agrees not to undergo elective intraocular surgery in the study eye (e.g., cataract extraction) for three months after the last injection.
• Participant has not received a periocular or intravitreal injection in the study eye in the last six weeks.
• Participant has necrotizing scleritis in the study eye.
• Participant had intraocular surgery in the study eye in the last four weeks.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996 Apr;80(4):332-6. doi: 10.1136/bjo.80.4.332.

  PMID: 8703885 BACKGROUND

• Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469-76. doi: 10.1016/s0002-9394(00)00710-8.

  PMID: 11024419 BACKGROUND

• Sen HN, Suhler EB, Al-Khatib SQ, Djalilian AR, Nussenblatt RB, Buggage RR. Mycophenolate mofetil for the treatment of scleritis. Ophthalmology. 2003 Sep;110(9):1750-5. doi: 10.1016/S0161-6420(03)00570-0.

  PMID: 13129873 BACKGROUND

• Bhatt N, Dalal M, Tucker W, Obiyor D, Nussenblatt R, Sen HN. Subconjunctival sirolimus in the treatment of autoimmune non-necrotizing anterior scleritis: results of a phase I/II clinical trial. Am J Ophthalmol. 2015 Mar;159(3):601-6. doi: 10.1016/j.ajo.2014.12.009. Epub 2014 Dec 17.

  PMID: 25526946 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Scleritis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Scleral Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: H. Nida Sen, MD, MHSc, Principal Investigator, NEI
• Organization: National Institutes of Health

senh@nei.nih.gov

301-402-3254

Study Officials

• Hatice N Sen, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 25, 2012
• Study Start: January 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: April 1, 2014
• Last Updated: June 19, 2020
• Results First Posted: June 10, 2014

Record last verified: 2016-08

Locations

US (1)