A Proof-of-concept Trial to EvaluAte the efficaCy and Safety Of Cell Therapy TRX103 in Patients With Active, Non-infectious Uveitis

Who can take part

• ≥ 18 to ≤ 70 years of age at time of consent
• Weight of ≥ 40 kg at time of consent
• Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits
• Diagnosis of active non-infectious uveitis (NIU); intermediate, posterior, or panuveitis at screening as defined as having at least ONE of the following findings:; .≥ 2+ VH (NEI/SUN Scale) OR; Active inflammatory chorioretinal or inflammatory retinal lesion or lesions as defined by fluorescein angiography (FA) or optical coherence tomography (OCT)
• Subjects on treatment with corticosteroids may be included if they meet the following:; Prednisone ≤ 20 mg/day; or an equivalent dose of another corticosteroid; Have been on a stable dose for at least 7 days prior to TRX103 dose; No ongoing treatment with a systemic non-corticosteroid, biologic, small molecules or immunomodulatory agent
• If the patient is on specific therapies such as systemic non-corticosteroid biologic agents, immunomodulatory agents or small molecules etc., appropriate washout periods defined in the protocol must be met prior to infusion at Day 0

Who cannot take part

• Any of the following ongoing treatments or anticipated use of any of the following treatments prior to TRX103 dose, for the time periods specified below:; Systemic immunosuppressants or immunomodulatory drugs within 4 weeks; Small molecules, e.g., JAK inhibitors or TYK2 inhibitors within 4 weeks; Anti-vascular endothelial growth factor (anti-VEGF) therapy within 8 weeks; TNF inhibitor therapy within 8 weeks; Agents that modulate T cells within 3 months; IL-6 inhibitors within 8 weeks; Therapeutic agents targeted to IL-17 within 4 months; Agents that modulate B cells within 6 months; Therapeutic agents targeted to IL-12 or IL-23 within 6 months
• Has received intraocular or periocular (including subtenon, intracanalicular) corticosteroids within 8 weeks prior to TRX103 dose, unless otherwise specified below:; Retisert® or Yutiq® (glucocorticosteroid implants) within 3 years prior or has had complications related to the implant; Retisert® (glucocorticosteroid implant) removed within 3 months prior or has had complications related to device removal; Ozurdex® (dexamethasone implant) or Xipere™ (suprachoroidal triamcinolone) within 4 months prior
• Ocular surgery within 90 days prior to TRX103 dose in the study eye, including glaucoma surgery (trabeculectomy or aqueous shunt device), and vitreoretinal surgery. Nd: YAG capsulotomy within 30 days prior to TRX103 dose in the study eye is also an exclusion criterion
• Subjects who are breastfeeding, pregnant, or planning to become pregnant, or subjects of childbearing potential who are unwilling to apply a highly effective birth control method prior to TRX103 dose
• Live vaccine within 6 weeks prior to Day 0 (day of infusion) or expected to need a live vaccine during the study
• Active bacterial, viral, fungal, mycobacterial, or other infections that would require treatment. Active infections must be resolved prior to enrollment
• Have required management of infections as follows:; Currently on suppressive therapy for any chronic infection; Hospitalization for infection within past 60 days; Use of IV or IM antibacterials, antivirals, antifungals, or anti- parasitic agents within past 60 days; History of disseminated herpes zoster, history of or invasive HSV, or recurrent (≥ 2 episodes within last 5 years) localized herpes zoster; Infection with Mycobacterium tuberculosis (TB); Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative; Hepatitis C virus (HCV RNA detectable in any subject with anti-HCV antibodies); Positive serology for HIV; Lab test results indicating active syphilis infection
• History of significant trauma or major surgery within 4 weeks prior to TRX103 dose or scheduled to undergo major surgery during the study
• Prior organ transplant, or allogeneic bone marrow, peripheral blood, or cord blood stem cell transplant
• Received another investigational agent or therapy, within 28 days of planned TRX103 infusion (or 5 half-lives, whichever is longer) and/or have not recovered from treatment related toxicities
• Participation in any other clinical trial/ or receiving any other investigational treatment while enrolled in this study
• Any condition preventing evaluation/assessment of both eyes
• Any significant ocular disease that could compromise vision
• Has ocular masquerade syndrome, like ocular lymphoma
• Any of the following cardiovascular risk factors:; History of NYHA Class III or IV criteria cardiac insufficiency; Clinically significant cardiac dysrhythmia; QTcF > 450 msec (male) or > 470 msec for (female); Unstable angina in last 3 months; Myocardial infarction within past year; CABG surgery past year
• History of blood transfusion within the last 3 years
• Subjects with a history of any other significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support such dysfunction
• Impaired kidney function, defined as any of the following:; Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula or as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation < 40 mL/min/1.73 m2; Proteinuria, defined as urine protein/creatinine ratio > 25; Symptomatic nephrolithiasis within 6 months of screening
• Screening laboratory and other analyses show any of the following abnormal results:; Serum aspartate transaminase or alanine transaminase > 3.0 × upper limit of normal; Bilirubin ≥ 2 x ULN; Total white blood cell count < 2,000/μL; Hemoglobin < 8 g/dL; Platelet count < 100,000/μL; Absolute neutrophil count < 1,200/μL; Absolute lymphocytes count < 750/μL
• Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results, which, in the Investigator's opinion:; Places the subject at increased risk during participation in the study, and/or; Interferes with the subject's capacity to provide informed consent and their participation in the study, and/or; interferes with the interpretation of the results
• Age-related macular degeneration or serpiginous choroidopathy
• Proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to non-uveitis causes
• Isolated anterior uveitis
• Macular edema as the only sign of uveitis, defined on OCT without active anterior/posterior inflammatory signs
• Myopic degeneration with active sub-foveal choroidal neovascularization
• Confirmed or suspected current infectious uveitis
• Anaphylaxis to fluorescein or unwillingness to undergo fluorescein angiograms