Study of the Safety, Tolerability, and Bioactivity of Tocilizumab On Patients With Non-infectious UVEITIS: The STOP-UVEITIS Study

NCT01717170 | Unknown Phase 1

• 1 other identifier: ML28522
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

In the STOP-UVEITIS study, we propose to evaluate the safety, tolerability, and bioactivity of two doses of Tocilizumab (4mg/kg and 8mg/kg), administered monthly, in patients with non-infectious intermediate, posterior, or panuveitis.

Conditions

Intermediate Uveitis; Posterior Uveitis; Pan-uveitis

Keywords

Non-infectious Uveitis, Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Frequency and severity of adverse events from baseline (BL) to month 6.

  Safety and tolerability of repeated Tocilizumab infusions in patients with non-infectious uveitis, as assessed by frequency and severity of adverse events from baseline (BL) to month 6.

  Baseline (BL) to month 6.

Secondary Outcomes (1)

• Frequency and severity of adverse events at month 12.

  Baseline to Month 12

Other Outcomes (1)

• Percentage of patients with a decrease of ≥ 2 steps in vitreous haze or resolution of haze (for patients with 1+ haze at baseline) based on the National Eye Institute (NEI) scale at 1, 3, 6, and 12 months after therapy or at time of rescue.

  Months 1, 3, 6, and 12 after therapy or at the time of rescue therapy administration.

Study Arms (2)

Tocilizumab (4 mg/kg)

EXPERIMENTAL

Tocilizumab (4 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.

Drug: Tocilizumab

Tocilizumab (8 mg/kg)

EXPERIMENTAL

Tocilizumab (8 mg/kg) as an intravenous infusion over 1 hour at day 0, 30, 60, 90, 120, and 150.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab (4 mg/kg or 8 mg/kg)

Also known as: ACTEMRA

Tocilizumab (4 mg/kg); Tocilizumab (8 mg/kg)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18;
• Able to give informed consent and attend all study visits;
• Have diagnosis of uveitis determined by the Investigator to be non-infectious;
• Have active uveitis, defined as having at least 1+ Vitreous Haze (SUN scale) in study eye. As mentioned above, at least 12 of the randomized subjects must also have vitreous haze of ≥ 2+ vitreous haze. and:
• are receiving no other treatment; or,
• are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) and/or at least 1 other systemic immunosuppressant;
• Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component is present, it must be less than the posterior component;
• Sufficient inflammation to require systemic treatment or long-term regional treatment. Patients whom the investigators feel may only need short-term topical therapy should not be enrolled.
• Best-corrected EARLY TREATMENT DIABETIC RETINOPATHY STUDY(ETDRS) visual acuity of 20/20 to 20/400 (approximately 80 to 20 letters) in the study eye;
• Best- corrected ETDRS visual acuity of 20/400 or better in the fellow eye (approximately 20 letters).
• Must have a chest radiograph within 3 months prior to enrollment with no evidence of malignancy, infection or fibrosis.
• Females of childbearing potential must have a negative serum pregnancy test at screening. In addition, sexually active females of childbearing potential must agree to use TWO of the following adequate forms of contraception while on study medication: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner.
• Males must agree to use barrier contraception (latex condoms) when engaging in sexual activity while on study medication and for 28 days after taking the last dose of study medication.
• Subjects with a documented history of non-infectious intermediate-, anterior and intermediate, posterior, or pan-uveitis including but not restricted to: intermediate uveitis, sarcoidosis, Vogt-Koyanagi-Harada (VKH) syndrome, birdshot retinochoroidopathy, retinal vasculitis, sympathetic ophthalmia, multifocal choroiditis with panuveitis. Prior to study screening, potential subjects must have been evaluated and screened for infectious etiologies by the investigators, possibly as part of standard clinical acre; all testing to rule out infectious causes must be performed within 3 months of screening for the STOP-UVEITIS study.
• Currently active and uncontrolled uveitis (of the types mentioned above) that at the determination of the investigator, requires the initiation of corticosteroid monotherapy at a dose of ≥ 10 mg/day (or equivalent) or prednisone therapy and immunomodulatory therapy or injections of corticosteroid (intravitreal or periocular); or uveitis in subjects for whom oral corticosteroid is contraindicated, relatively or absolutely.

You may not qualify if:

• Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:
• Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision.
• Age-related macular degeneration;
• Myopic degeneration with active subfoveal choroidal neovascularization.
• Advanced glaucoma status post trabeculectomy or tube/valve placement
• Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:
• Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors);
• Posterior subtenon's steroids
• Intraocular surgery within 90 days prior to Day 0 in the study eye;
• Capsulotomy within 30 days prior to Day 0 in the study eye;
• History of vitreoretinal surgery or scleral buckling
• Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following Day 0;
• Intraocular pressure (IOP) ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP \<25 mmHg are allowed to participate);
• Pupillary dilation inadequate for quality stereoscopic fundus photography in the study eye;
• Media opacity that would limit clinical visualization;

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

Truhlsen Eye Institute, University Of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

Related Publications (1)

• Sadiq MA, Hassan M, Afridi R, Halim MS, Do DV, Sepah YJ, Nguyen QD; STOP-UVEITIS Investigators. Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study. Int J Retina Vitreous. 2020 Oct 6;6:47. doi: 10.1186/s40942-020-00245-w. eCollection 2020.

  PMID: 33042579 DERIVED

MeSH Terms

Conditions

Uveitis, Intermediate; Uveitis, Posterior

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Uveitis; Uveal Diseases; Eye Diseases; Panuveitis

Study Officials

• Quan D Nguyen, MD, MSc

  Truhlsen Eye Institute, University of Nebraska Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: October 30, 2012
• Study Start: March 1, 2013
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

US (1)