NEW Study: Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes (STACCATO)
ClinicalTrials.gov Identifier: NCT03586284
Sponsor: University of California, San Francisco
Purpose: A double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 99
Inclusion Criteria: Clinical impression consistent with CMV anterior uveitis. Directed PCR positive for CMV OR previous PCR-proven CMV anterior uveitis. Willingness to use an acceptable method of contraception during the study period (i.e. pharmacologic, devices, barrier methods) or abstinence.
Exclusion Criteria: Patients <18 years of age. Intermediate or posterior inflammation (involvement of vitreous, choroid, or retina). Received antiviral therapy <14 days prior to enrollment. Received periocular or intraocular corticosteroid injection < 8 weeks prior to enrollment. Currently taking oral corticosteroids. Immunocompromised (primary or secondary immunosuppressive disorders). Prior immunosuppressive therapy in the past 6 months. Directed PCR negative for CMV. Directed PCR positive for herpes simplex virus (HSV) or varicella zoster virus (VZV). Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females of child-bearing age is mandatory within 4 weeks prior to enrollment). Complete blood count with white blood cell, absolute neutrophil, or platelet count lower than the lower limit of reference laboratory normal. BUN or Cr above the upper limit of reference laboratory normal. Recent ocular surgery within the past 30 days, or planned surgery within the next 45 days. Systemic autoimmune disease or ocular condition (besides anterior uveitis) anticipated to dictate or alter treatment course.
Paused due to COVID-19 Study: Efficacy and Safety of H.P. Acthar Gel in Subjects with Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis NIPPU
ClinicalTrials.gov Identifier: NCT03656692
Purpose: The primary objective of this study is to explore the efficacy of Acthar in participants with severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU). in reducing aqueous and vitreous indicators of inflammation.
Design: Single group, open label
Number of Patients: 30
Inclusion Criteria: Participants must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the ICF. Participants must be ≥18 years of age at screening visit and can be male or female. Participants must have been diagnosed with current severe NIPPU and have active disease at the baseline visit as defined by the presence of at least 1 of the following parameters in at least 1 eye despite at least 2 weeks of maintenance therapy with oral prednisone 10 mg/day to ≤60 mg/day (or oral corticosteroid equivalent): Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion. ≥2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria). ≥2+ vitreous haze (Nussenblatt et al, 1985). Participants entering the study on 1 concomitant immunosuppressive therapy must not have had the dose increased in the 2 weeks prior to the baseline visit and must be within the following allowable doses at the baseline visit: Methotrexate ≤15 mg per week. Cyclosporin ≤4 mg/kg per day. Mycophenolate mofetil ≤2 g per day or an equivalent drug (eg, mycophenolic acid) at an equivalent dose that has been approved by the medical monitor (MM). Azathioprine ≤175 mg per day. Tacrolimus (oral formulation) ≤8 mg per day. Adalimumab 40 mg SC every other week. Participants must be willing to taper their current doses of corticosteroid and immunomodulatory therapy to the minimum effective dose during the study. Female Participants must be of nonchildbearing potential (history of hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or postmenopausal with no history of menstrual flow in the 12 months prior to the screening visit); or if of childbearing potential must be nonpregnant, nonlactating and agree to use effective contraception when with a male partner throughout study participation (through the Follow-up visit). Acceptable forms of contraception include hormonal measures (oral contraceptive pills, contraceptive patch, contraceptive ring, injections), intrauterine devices, double barrier method (condom plus diaphragm, condom or diaphragm plus spermicidal gel or foam), and abstinence.
Exclusion Criteria: Participant is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc.) or a family member of the research staff conducting the study, or of the sponsor, or of the clinical research organization, or of the IRB/IEC. Participant has a history of sensitivity to ACTH preparations or sensitivity to porcine protein products. Participant has had recent (within the previous 6 months) diabetic retinopathy, age-related macular degeneration, intraocular surgery or ocular trauma, cataracts, or posterior capsule opacification. Participant is under treatment with any corticosteroids, immunosuppressants, immunomodulators, or biologic agents for a concomitant condition (eg, rheumatoid arthritis under treatment with a tumor necrosis factor- alpha [TNF-α] drug). Participants are specifically excluded for any of the following: Participant has received (glucocorticosteroid implant) within 3 years prior to the baseline visit or has had complications related to the device and/or Participant has had removal within 90 days prior to the baseline visit or has had complications related to the removal of the device. Participant has received intraocular or periocular corticosteroids within 30 days prior to baseline visit. Participant has proliferative or severe nonproliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy. Participant has neovascular/wet age-related macular degeneration. Participant has an abnormality of a vitreoretinal interface (ie, vitreomacular traction, epiretinal membranes, etc) with the potential for macular structural damage independent of the inflammatory process. Participant has a severe vitreous haze that precludes visualization of the fundus at the baseline visit. Participant has any known contraindication(s) to Acthar (Mallinckrodt Package Insert, 2018) including, but not limited to: Any known history of scleroderma, osteoporosis, or ocular herpes simplex. For the purposes of this study, osteoporosis is defined as evidence of current vertebral or long bone fracture, or lumbar T-score >2.0 SD below the mean of the reference population. Any primary adrenocortical insufficiency, or adrenal cortical hyperfunction. Any current congestive heart failure (defined as New York Heart Association. Participant has a history of chronic active hepatitis including active or chronic hepatitis B, or acute or chronic hepatitis C. Participant has a history of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact with an individual with an active TB infection. Participant has known immune compromised status (not related to disease/condition under study), including but not limited to, individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus. Participant has any solid tumor malignancy currently diagnosed or undergoing therapy, or has received therapy for any solid tumor malignancy in the 5 years prior to the screening visit; with the exception of treated and cured basal cell carcinoma, treated and cured squamous cell carcinoma of the skin, and treated and cured carcinoma in situ of the cervix. Participant has any of the following laboratory abnormalities at the screening visit: Hemoglobin ≤8.0 g/dL. Platelets ≤50,000 cells/μL. Absolute neutrophil count (ANC) ≤1000 cells/μL. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin 2 times upper limit of normal (ULN). Glycosylated hemoglobin (HbA1c) 6.5. Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive Hepatitis C virus antibody (HCV). (If HCV is positive at screening, HCV polymerase chain reaction [PCR] will be automatically analyzed. Participants with a positive HCV must have HCV PCR <25 IU/mL at the screening visit to be eligible). Participant has any other clinically significant disease, disorder or laboratory abnormality (including those listed on the Prescribing Information Section 5: Warnings and Precautions [Mallinckrodt Package Insert, 2018]) which, in the opinion of the investigator (by its nature or by being inadequately controlled), might put the patient at risk due to participation in the study, or may influence the results of the study or the Participant's ability to complete the study.
Study: A 48 Week Study to Evaluate the Efficacy and Safety of Two (2) EYS606 Treatment Regimens in Subjects With Active Chronic Non-infectious Uveitis (CNIU) (ELECTRO)
ClinicalTrials.gov Identifier: NCT04207983
Purpose: The objective of the study is to evaluate the efficacy and safety of two different treatment regimens of EYS606.
Design: Randomized, parallel assignment
Number of Patients: 56
Inclusion Criteria: Subject must be 18 years of age or older. Subject must have a diagnosis of chronic non-infectious uveitis of any anatomic subtype (anterior, intermediate, posterior or panuveitis). Subject must have a history of chronic or recurrent non-infectious uveitis requiring or having required treatment with corticosteroids (systemic, periocular or intraocular) and/or systemic immunosuppressive medication(s) in the 12 months prior to the screening visit. Best corrected visual acuity of Study Part I: ≥ 5 and < 67 ETDRS letters in the study eye (equivalent to less than or equal to 20/50 but better than or equal to 20/800 Snellen). Study Part II: ≥ 5 and < 77 ETDRS letters in the study eye (equivalent to less than or equal to 20/32 but better than or equal to 20/800 Snellen). At the screening and baseline visits subject must have active chronic non-infectious uveitis as evidenced by at least one or more of the following in the study eye: Active retinal vasculitis (retinal vascular leakage) involving the posterior pole confirmed by the reading center. Vitreous haze grade ≥ 2+ (SUN classification). Anterior chamber cell grade ≥ 2+ (SUN classification); anterior chamber cells must be present for subjects with a diagnosis of chronic anterior non-infectious uveitis. Persistent macular edema (defined as central retinal thickness (CRT) > 300 microns or > 320 microns using Zeiss Cirrus and Topcon or Heidelberg Spectralis spectral domain ocular coherence tomography (SD-OCT) instruments, respectively) despite treatment with corticosteroids and/or immunosuppressive therapy for at least 4 weeks prior to screening. Subject receiving concomitant topical and/or systemic corticosteroids or allowed systemic immunosuppressive medications must have maintained the same treatment regimen (dosage/frequency) for at least 2 weeks prior to the baseline (V1) visit, (if applicable).
Study: Efficacy and Safety of H.P. ACTHAR GEL in Adults with Retinal Vasculitis
ClinicalTrials.gov Identifier: NCT03066869
Sponsor: Ocular Immunology and Uveitis Foundation
Purpose: The purpose of this study is to evaluate the short- and long-term efficacy and safety of Acthar for the treatment of adults with non-infectious retinal vasculitis.
Design: Single group, no masking
Number of Patients: 40
Inclusion Criteria: Any adult patient with active retinal vasculitis (involving arteries or veins) as a manifestation of non-infectious ocular inflammatory disease; fundus must be viewable with wide-field FA in the study eye. If both eyes are involved, both are eligible for inclusion in the study. Patients already on nonsteroidal immunosuppressive therapy may continue on this during the study, but the dose must not be increased or decreased within 6 weeks of initiating the trial. Willing and able to sign the informed consent form.
Exclusion Criteria: Patients under age 18. Patients who are pregnant (must be ruled out in women of child-bearing age). Active infectious ocular or systemic disease. Patients with active infectious ocular or extraocular disease. Patients with history of malignancy, except for dermatologic entities of basal or squamous cell carcinoma which have been completely excised or removed previously. Patients with systemic illness involving abnormalities of the hypothalamic-pituitary-adrenal axis; patients with primary adrenocortical insufficiency or adrenocortical hyperfunction. Patients with known hypersensitivity to Acthar. Patients on other non-steroidal systemic immunomodulatory medications with dose adjusted sooner than 6 weeks prior to study drug administration. Patients currently on or recently treated with (within 6 weeks) systemic corticosteroid. Patients with periocular or intraocular injections of medications administered to help control inflammation sooner than 6 weeks prior to study drug administration. Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator, or contraindicated, including but not limited to, patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine origin. Administration of live or live attenuated vaccines is contraindicated in patients during the entire duration of the study and for 1 month prior.
Study: Assessment of the Anti-inflammatory Effects of Norflo Oro in Acute Relapses of HLA-B27 Associated Autoimmune Uveitis
ClinicalTrials.gov Identifier: NCT03584724
Sponsor: Eye Pharma; Bascom Palmer Eye Institute
Purpose: The purpose of this study is to explore the efficacy of Norflo Oro in the treatment of relapsing autoimmune uveitis (RAU), measured as a long term reduction of the frequency and the severity of relapses, in patients with HLA-B27 associated uveitis, under conditions of routine medical practice. The reduction of the mean number of relapses per patient between the year before study treatment and the study period will also be assessed.
Design: Randomized, parallel assignment, quadruple masking
Number of Patients: 5
Inclusion Criteria: Clinical diagnosis of HLA-B27 positive related uveitis in nonacute phase. At least 1 autoimmune uveitis relapse.
Exclusion Criteria: Use of supplements (nutraceuticals) or systemic therapy for uveitis with anti-inflammatory immunosuppressive or biological drugs within last 30 days. Anticipated need for systemic anti-inflammatory treatment during the study. Use of intravitreal peribulbar, sub-tenon, periocular injection in the previous 6 months. Long-term treatment with a systemic anti-inflammatory, immune suppressant drugs. Woman taking hormonal contraceptives, pregnant or breastfeeding.
Study: Tofacitinib for Inflammatory Eye Disease
ClinicalTrials.gov Identifier: NCT03580343
Sponsor: Washington University School of Medicine
Purpose: Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, autoimmune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and/or scleritis.
Design: Single group, no masking
Number of Patients: 5
Inclusion Criteria: Diagnosis of uveitis; a clinical response to steroids; active disease requiring at least 10mg of prednisone daily (or steroid equivalent).
Exclusion Criteria: Suspected or confirmed ocular infection; chronic or recurring infections, such as HIV; renal insufficiency that would preclude safe administration of tofacitinib.
Study: Adalimumab vs Conventional Immunosuppression for Uveitis Trial (ADVISE)
ClinicalTrials.gov Identifier: NCT03828019
Sponsor: JHSPH Center for Clinical Trials
Purpose: Based upon preliminary data, adalimumab, a fully-human, anti-TNF-α monoclonal antibody, now US FDA-approved for uveitis treatment, may be a superior corticosteroid-sparing agent than conventional immunosuppressive drugs. The ADVISE Trial is multicenter randomized, parallel-treatment, comparative effectiveness trial comparing adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in the treatment of non-infectious, intermediate, posterior, and panuveitides.
Design: Randomized, parallel assignment, no masking
Number of Patients: 222
Inclusion Criteria: Age 13 years or older; active or recently active (≤60 days) non-infectious, intermediate, posterior, or panuveitis; prednisone indication meets one of the following: a. Active uveitis requiring one of the following i. Initiation of prednisone at dose greater than 7.5 mg/day ii. Increasing prednisone dose to greater than 7.5 mg/day iii. Currently receiving dose greater than 7.5 mg/day; b. Inactive uveitis on current dose greater 7.5 mg/day. Initiation or addition of an immunosuppressive drug (ie, a conventional immunosuppressive drug or adalimumab) is indicated. If currently receiving a conventional immunosuppressive drug, the drug and dose have been stable for at least 30 days. Patient able and willing to self-administer subcutaneous injections or have a qualified person available to administer subcutaneous injections. If posterior segment disease is present, ability to assess activity in at least 1 eye with uveitis. Visual acuity of light perception or better in at least 1 eye with uveitis.
Exclusion Criteria: Active tuberculosis or untreated latent tuberculosis (eg, positive interferon-γ release assay [IGRA] test, such as Quantiferon-gold). Untreated active hepatitis B or C infection. Behçet disease. Multiple sclerosis. For patients with intermediate uveitis, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease. Use of anti-TNF monoclonal antibody therapy within past 60 days. History of adalimumab intolerance or ineffectiveness. Current treatment with an alkylating agent. Current treatment with more than 1 immunosuppressive drug, not including oral corticosteroids. Shorter-acting regional corticosteroids administered within the past 30 days in any eye(s) with uveitis. Long-acting ocular corticosteroid implants, ie, fluocinolone acetonide implant (eg, Retisert, Yutiq, Iluvien) placed within past 3 years unless uveitis is active in all eye(s) with an implant. Systemic disease that is sufficiently active such that it dictates therapy with systemic corticosteroids or immunosuppressive agents at the time of enrollment. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated according to best medical judgment. Pregnancy, lactation, or for women of child-bearing potential unwillingness to use appropriate birth control for the duration of the trial. Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.
Study: OCT Technology Development to Assess Ocular Integrity and Characterize Ocular Integrity and Intraocular Scatterers
ClinicalTrials.gov Identifier: NCT03531853
Sponsor: Duke University
Purpose: The purpose of this study is to develop and demonstrate new technologies that will enable a non-contact, compact eye imaging system based on OCT to assist an early responder in acute care settings (like an emergency room) to help assess eye trauma and inflammation (swelling inside the eye).
Design: Single group, open label
Number of Patients: 75
Inclusion Criteria: Pre-clinical: employees or students (over the age of 18) of the Duke Eye Center or Biomedical Engineering willing to be imaged with OCT system; pilot (ER): patients (over the age of 18) presenting emergently to the Duke Emergency room with traumatic eye injuries and/or suspected open globe; pilot uveitis): patients presenting to the Duke Eye Center with active uveitis and microhyphema or hyphema; patients who have independently consented to undergo vitreous tap or biopsy for their uveitis care at the Duke Eye Center.
Exclusion Criteria: Preclinical: subject cannot be a direct report to any of the PIs or other key personnel of this study; pilot (ER): hemodynamically unstable, unable to consent; pilot (Uveitis): unable to consent; cornea or lens opacity/scar which would block the imaging modality.
Study: A Phase III Study Assessing the Efficacy and Safety of Intravitreal Injections of 440 ug DE-109 for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye (LUMINA)
ClinicalTrials.gov Identifier: NCT03711929
Sponsor: Santen Inc.
Purpose: This is a Phase III study to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS).
Design: Randomized, parallel assignment, quadruple-blind, treatment
Number of Patients: 200
Inclusion Criteria: Noninfectious active uveitis of the posterior segment.
Exclusion Criteria: Females who are pregnant, nursing, or planning a pregnancy; confirmed or suspected infectious uveitis.
Study: ACTH as A Re-emerging theRapy for Uveitis (The ACTHAR Study) (ACTHAR)
ClinicalTrials.gov Identifier: NCT02931175
Sponsor: Quan Dong Nguyen
Purpose: The study aims to evaluate the potential role of ACTH gel in the management of non-infectious uveitis.
Design: Randomized, parallel assignment, no masking
Number of Patients: 36
Inclusion Criteria: In order to be eligible for the study, patients will be required to meet the criteria of 1 of the 3 following disease cohorts: Active disease and are receiving no treatment. Active disease is defined as having at least 1+ Vitreous Haze using the Standardized Uveitis Nomenclature (SUN) Working Group scale and/or at least 1+ Vitreous Cell Count using Foster & Vitale scale. Active disease and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category. Have inactive disease, defined as having <= 0.5+ Vitreous Haze OR <= 0.5+ Vitreous Cell Count (SUN scale), and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category.
Exclusion Criteria: Subjects who have any of the following at the screening visit are not eligible for enrolment in this study: 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; Any known 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; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Presence of ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and non-ocular clinical trials. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Prior treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are anti-cluster of differentiation (CD) 4, anti- cluster of differentiation (CD)5, anti-cluster of differentiation (CD) 3, anti-cluster of differentiation (CD)19 and anti-cluster of differentiation (CD)20. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline. Immunization with a live/attenuated vaccine within 4 weeks prior to baseline. Previous treatment with ACTHAR within 3 months of day 0 of study visit. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Study: Humboldt: Efficacy and Safety of Filgotinib in Adults with Active Noninfectious Uveitis
ClinicalTrials.gov Identifier: NCT03207815
Sponsor: Gilead Sciences
Purpose: The primary objective of this study is to evaluate the efficacy of filgotinib vs placebo for the treatment of the signs and symptoms of noninfectious uveitis in participants failing treatment for active noninfectious uveitis.
Design: Randomized, parallel assignment, double masking, treatment
Number of Patients: 110
Inclusion Criteria: Is diagnosed with noninfectious intermediate-, posterior-, or panuveitis; Must have active uveitic disease at the day 1/baseline visit as defined by the presence of at least 1 of the following parameters in at least 1 eye despite 2 weeks or more of maintenance therapy with oral prednisone (≥10 mg/day to ≤60 mg/day) or oral corticosteroid equivalent: Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion; ≥2+ anterior chamber cells per the Standardization of Uveitis Nomenclature (SUN) criteria; ≥2+ vitreous haze per the National Eye Institute/Standardization of Uveitis Nomenclature (NEI/SUN) criteria. No evidence of active tuberculosis (TB), history of prior TB or latent TB meeting the screening criteria.
Exclusion Criteria: Adults with severe glaucoma at screening are not eligible to participate; severe glaucoma is defined as: Intraocular pressure of ≥25 mmHg and on ≥2 glaucoma medications and/or; Any evidence of glaucomatous optic nerve injury. Confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV). Adults with a prior failure of anti-tumor necrosis factor (TNF) therapy or previous exposure to any biologic therapy (except intravitreal anti-vascular endothelial growth factor [VEGF] therapy) with a potential therapeutic impact on noninfectious uveitis within 90 days of day 1/ baseline are not eligible to participate.
Study: MERIT: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
ClinicalTrials.gov Identifier: NCT02623426
Sponsor: JHSPH Center for Clinical Trials
Purpose: This trial will compare the relative efficacy and safety of intravitreal methotrexate, intravitreal ranibizumab, and the intravitreal dexamethasone implant for the treatment of uveitic macular edema persisting or reoccurring after an intravitreal corticosteroid injection. MERIT is a parallel design (1:1:1), randomized comparative trial with an anniversary close-out at the 6-month clinic visit. The primary outcome is percent change in central subfield thickness from the baseline OCT measurement to the 12 week visit.
Design: Randomized, parallel assignment, single masking, treatment
Number of Patients: 240
Inclusion Criteria: 18 years of age or older; at least 1 eye must meet all of the following conditions; Inactive or minimally active noninfectious anterior, intermediate, posterior or panuveitis, as defined by SUN132 criteria as ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze grade and no active retinal/choroidal lesions for a minimum of 4 weeks; Macular edema (ME) defined as the presence of macular thickness greater than the normal range for the OCT machine being used (see cut points below), regardless of the presence of cysts, following an intravitreal corticosteroid injection (≥4 weeks following intravitreal triamcinolone injection or ≥12 weeks following intravitreal dexamethasone implant injection); Greater than 300 μm for Zeiss Cirrus Greater than 320 μm for Heidelberg Spectralis Greater than 300 μm for Topcon 3DOCT; baseline fluorescein angiogram that, as assessed by the study ophthalmologist, is gradable for degree of leakage in the central subfield; Best corrected visual acuity (BCVA) 5/200 or better; baseline intraocular pressure >5 mm Hg and ≤21 mm Hg (current use of ≤3 intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable (Note: combination medications, eg, Combigan, are counted as 2 IOP-lowering medications); Media clarity and pupillary dilation sufficient to allow OCT testing and assessment of the fundus.
Exclusion Criteria: History of infectious uveitis in either eye; History of infectious scleritis of any type in either eye (Note: History of noninfectious scleritis that has been active in past 12 months is an eye-level exclusion -see #13 below); History of keratitis (with the exception of keratitis due to dry eye) in either eye; History of central serous retinopathy in either eye; Active infectious conjunctivitis in either eye; Oral prednisone dose >10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤10 mg per day at baseline that has not been stable for at least 4 weeks (note: if patient is off of oral prednisone at baseline (M01 study visit) dose stability requirement for past 4 weeks does not apply); Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks (note: use of systemic methotrexate is acceptable as long as regimen has been stable for at least 4 weeks); Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline; Known allergy or hypersensitivity to any component of the study drugs; For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial; Eye level exclusion criteria - at least 1 eye that meets all inclusion criteria cannot have any of the following conditions: History of infectious endophthalmitis; History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥0.9 or any notching of optic nerve to the rim); History of active noninfectious scleritis in past 12 months (Note: History of noninfectious scleritis is acceptable if the last episode of active scleritis resolved at least 12 months prior to enrollment); Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (ie, causing substantial wrinkling of the retinal surface); Torn or ruptured posterior lens capsule; Presence of silicone oil; Ozurdex administered in past 12 weeks; Anti-VEGF agent, intravitreal methotrexate, or intravitreal/periocular corticosteroid administered in past 4 weeks; Fluocinolone acetonide implant (Retisert) placed in past 3 years.
Study: STAR Study: Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
ClinicalTrials.gov Identifier: NCT02911116
Sponsor: National Eye Institute (NEI)
Purpose: The study objective is to investigate the safety, tolerability and potential efficacy of subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.
Design: Prospective, nonrandomized, uncontrolled
Number of Patients: 7
Inclusion Criteria: Participant has the ability to understand and sign the informed consent document; Participant is 18 years of age or older; Participant has negative purified protein derivative (PPD) or quantiferon testing done within 3 months prior to enrollment or had latent tuberculosis (TB) but has completed prophylactic anti-TB treatment; Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least 1 eye requiring systemic therapy. Participant has visual acuity in at least 1 eye of 20/400 or better. 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 testing 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 2 effective methods of contraception throughout the course of the study and for 6 weeks after the last investigational product injection.
Exclusion Criteria: Participant has a significant active infection (an infection requiring treatment as determined by the medical team), including active tuberculosis or human immunodeficiency virus (HIV). Participant received a live vaccination within the past 6 weeks. Participant is expected to receive a live vaccination at any time during the study. Participant received the BCG vaccine within the past year. Participant is expected to receive the BCG vaccine at any time during the study or up to 1 year after discontinuing ustekinumab. Participant has a history of cancer (other than a nonmelanoma skin cancer) diagnosed within the past 5 years. Participant has received intraocular (or periocular) steroid or anti-vascular endothelial growth factor (VEGF) injections within the last 6 weeks. Participant received rituximab within the last 6 months or another biologic agent (eg, infliximab, daclizumab, adalimumab) within the last 2 months. Participant has received alkylating agents (eg, cyclophosphamide, chlorambucil) within the last 9 months. Participant has a known hypersensitivity to ustekinumab or any of its components.
Study: SAVE-2: Intravitreal Sirolimus as Therapeutic Approach to Uveitis
ClinicalTrials.gov Identifier: NCT01280669
Sponsor: Stanford University, Santen Inc.
Purpose: The purpose of this study is to find out about the safety and effectiveness of 2 different doses the study drug, sirolimus, administered intravitreally in patients with uveitis.
Design: Randomized, parallel assignment, no masking
Number of Patients: 30
Inclusion Criteria: >12 years of age, able to give consent, have diagnosis of uveitis, have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least 1+ Vitreous Cell Count (SUN scale), and: are receiving no treatment; or are receiving: prednisone ≥10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant. Have inactive disease, defined as having 0.5+ vitreous haze or less and 0.5+ or less vitreous cell count (SUN scale), and are receiving: prednisone <10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone <10 mg/day (or equivalent dose of another corticosteroid) and 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 and, based on the Investigator's decision, warrants intravitreal treatment. Best-corrected ETDRS visual acuity of 20/400 or better (approximately 20 letters) in the study eye. Best-corrected ETDRS visual acuity of 20/400 or better in the fellow eye (approximately 20 letters).
Exclusion Criteria: Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy (eg, methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the Investigator, cannot be controlled with standard local therapies alone; Any significant ocular disease that could compromise the visual outcome in the study eye. Intravitreal injections (including but not limited to anti-vascular endothelial growth factors 60 days prior to the baseline; Posterior subtenon's or intravitreal injection of steroids 90 days prior to baseline; 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 within 90 days prior to day 0 in the study eye; Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following day 0; Intraocular pressure ≥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 fundus photography in the study eye; Media opacity that would limit clinical visualization, intravenous fluorescein angiography (IVFA), or OCT evaluation in the study eye; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and nonocular clinical trials.