Gevokizumab for Active Scleritis

NCT01835132 | Completed Phase 1 Results DMC

• 2 other identifiers: 13010213-EI-0102
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Scleritis is the inflammation of the white outer coating of the eye, known as the sclera. In severe cases, it can cause blindness. It is commonly associated with autoimmune disorders such as rheumatoid arthritis. Mild scleritis can be treated with drugs such as ibuprofen. More severe scleritis may need oral steroids or immunosuppressive treatments; however, these treatments can cause side effects in the whole body. Gevokizumab is a newer anti-inflammatory drug that is under investigation to treat other inflammatory diseases. It may not have as severe side effects as some other drugs. However, it has not yet been used to treat scleritis. Researchers want to see if it can be given as a safe and effective treatment for scleritis. Objectives: \- To see if gevokizumab is a safe and effective treatment for scleritis. Eligibility: \- Individuals at least 18 years of age who have active scleritis. Design:

• There is an initial phase and a two-part extension phase in this study. The extension phase is optional. The initial phase of the study requires seven visits to the National Eye Institute (NEI).
• Participants will be screened with a physical exam and eye exam, and medical history will be obtained. Blood and urine samples will be collected.
• Eligible participants will receive an injection of 60 mg of gevokizumab at the first study visit and at Weeks 4, 8, and 12. They will be given under the skin by the stomach, or in the upper arm or thigh.
• Participants will have additional visits after the first study visit at Weeks 2, 16, and 28. No injection will be given at these visits. Eye exams will be done, and blood and tear samples will be collected.
• If the scleritis improves by Week 16, participants may choose to continue the study in the extension phase. In the 1st extension, they will have a visit every 4 weeks until Week 36 and then two additional monitoring visits at Weeks 40 and 52 for a total of 13 study visits.
• Participants who are eligible at Week 52 may continue in the "as needed" (PRN) extension phase (2nd extension) and receive gevokizumab injections (60 mg) at Weeks 52, 54, 58 and 62.

Conditions

Scleritis

Keywords

Scleritis; IL-1

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least a 2-step Reduction or Reduction to Grade 0 in Scleral Inflammation in the Study Eye (or Eyes), According to the National Eye Institute (NEI) Photographic Scleritis Grading System, on or Before the Week 16 Visit.

  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 16

Secondary Outcomes (36)

• Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 2 Compared to Baseline

  Baseline and Week 2

• Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 4 Compared to Baseline

  Baseline and Week 4

• Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 8 Compared to Baseline

  Baseline and Week 8

• Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 12 Compared to Baseline

  Baseline and Week 12

• Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 16 Compared to Baseline

  Baseline and Week 16

Study Arms (1)

Gevokizumab

EXPERIMENTAL

Subcutaneous injection of 60 mg gevokizumab

Device: Gevokizumab

Interventions

Gevokizumab DEVICE

Subcutaneous injection of 60 mg gevokizumab

Gevokizumab

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 have a diagnosis of non-infectious anterior scleritis requiring treatment.
• Participant must agree not to undergo elective major surgery for the first 16 weeks of the study.
• Participant must not have received any the following:
• Another systemic biologic immunosuppressive agent within the last three months prior to enrollment (e.g., infliximab, daclizumab, etanercept, adalimumab, anakinra);
• Rituximab or alkylating agent (e.g., cyclophosphamide) within the last 12 months prior to enrollment.
• Participants on systemic anti-inflammatory therapy (including corticosteroids) must not have had a dose escalation in any of their immunosuppressive treatments within the last four weeks prior to enrollment.
• Participant must stop all immunosuppressives upon enrollment in the study, with the exception of ≤ 20 mg/day of prednisone or equivalent.
• Participant must have chest X-ray results (frontal and lateral) within the last 12 weeks prior to enrollment with no evidence of active pulmonary infection, active tuberculosis (TB) or malignancy.
• Participant must be cleared by internal medicine for enrollment.
• Female participants of childbearing potential must not be pregnant or breast-feeding, must 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 a child 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

You may not qualify if:

• Participant has a significant active infection that requires treatment or has a history of recurrent systemic infections.
• Participant has a history of TB and s/he has not received a full course of TB treatment, OR participant has a history of latent TB infection \[or a positive Interferon-Gamma Release Assay (IGRA)\] and has not received prophylactic treatment with isoniazid \[also known as isonicotinylhydrazine (INH)\] or rifampicin within the last six months prior to enrollment.
• Participant is seropositive for human immunodeficiency virus (HIV) or Hepatitis C.
• Participant has a history of cancer (other than a non-melanoma skin cancer or carcinoma in situ of the cervix) diagnosed within the last five years.
• Participant has a history of severe allergic or anaphylactic reaction to monoclonal antibodies.
• Participant has a history of previous treatment with gevokizumab.
• Participant received live (attenuated) vaccine within the last three months prior to enrollment. Live seasonal flu and H1N1 vaccines are permitted ≥ two weeks prior to enrollment. Recombinant or killed vaccines are permitted at any time.
• Participant has received an investigational drug or device within the last three months.
• Participant has active joint or systemic inflammation requiring immediate addition or increase in systemic anti-inflammatory medications.
• Participant has a condition (e.g., psychiatric illness, severe alcoholism or drug abuse) or situation that may put the participant at significant risk, may confound the study results or may interfere significantly with his/her participation or cooperation in the study.
• STUDY EYE ELIGIBILITY CRITERIA:
• Participant must have scleritis with a grade of ≥ +1 in the study eye.
• Participant must have visual acuity of 20/640 or better in the study eye.
• Participant must agree not to undergo elective ocular surgery (e.g., cataract extraction) in the study eye for the first 16 weeks of the study.
• Participant has had any of the following in the study eye:

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 (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

• Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163-91. doi: 10.1136/bjo.60.3.163.

  PMID: 1268179 BACKGROUND

• Knickelbein JE, Tucker WR, Bhatt N, Armbrust K, Valent D, Obiyor D, Nussenblatt RB, Sen HN. Gevokizumab in the Treatment of Autoimmune Non-necrotizing Anterior Scleritis: Results of a Phase I/II Clinical Trial. Am J Ophthalmol. 2016 Dec;172:104-110. doi: 10.1016/j.ajo.2016.09.017. Epub 2016 Sep 20.

  PMID: 27663070 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Scleritis

Condition Hierarchy (Ancestors)

Scleral Diseases; Eye Diseases

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

Model Details: Subcutaneous injection of 60 mg gevokizumab

Study Record Dates

• First Submitted: April 16, 2013
• First Posted: April 18, 2013
• Study Start: March 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: February 1, 2016
• Last Updated: July 6, 2018
• Results First Posted: August 25, 2015

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)