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

Официальное название

A Proof-of-Concept Trial to EvaluAte the EfficaCy and Safety Of Cell Therapy TRX103 Administered Intravenously in Patients With Active, Non-infectious Intermediate, Posterior, and Pan-Uveitis - PEACOCX Study

Обзор

The purpose of this Phase 1, first in uveitis open-label study is to assess the safety and tolerability of TRX-103 in patients with non infectious uveitis (NIU). It is anticipated that up to 18 Subjects will be enrolled during a 18-24 month enrollment period. TRX-103 will be infused one time.

Вмешательства

• Биопрепарат TRX103
  TRX103 infusion via peripheral line

Первичные конечные точки

• Incidence of Treatment emergent Adverse events and Serious Adverse events at week 52 [Срок оценки: Up to a year]
• Incidence of infections, either bacterial, fungal or viral at week 52 [Срок оценки: Upto 1 year]
• Negative Replication Competent Lentivirus (RCL) at approximately 3-months, 6-months, and 12-months. [Срок оценки: At 3-month, 6-month, and 1-year.]

Вторичные конечные точки (3)

• Change in Best-Corrected Visual acuity (BCVA) at week 52, compared to Baseline [Срок оценки: Up to a year]
• Change in Central subfield thickness on OCT at week 52 from baseline [Срок оценки: Upto a year]
• Change in quality of life at week 52 using NEI VFQ 25 compared to Baseline [Срок оценки: Upto a year]

Критерии участия

Критерии включения

• ≥ 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.

Критерии исключения

• Any condition preventing evaluation/assessment of both eyes.
• Any significant ocular disease that could compromise vision.
• 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.
• Age-related macular degeneration or serpiginous choroidopathy.
• Myopic degeneration with active sub-foveal choroidal neovascularization.
• Confirmed or suspected current infectious uveitis.
• Has ocular masquerade syndrome, like ocular lymphoma.
• 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.
• 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.
• 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.
• 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.
• Anaphylaxis to fluorescein or unwillingness to undergo fluorescein angiograms.
• 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.
• History of blood transfusion within the last 3 years.
• 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.
• 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.
• Subjects with a history of any other significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support such dysfunction.
• 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.
• Participation in any other clinical trial/ or receiving any other investigational treatment while enrolled in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Byers Eye Institute — Palo Alto

Идентификаторы

NCT: NCT07427628 · TRX103-PEACOCX

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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