Overview
Ixekizumab for the Management of Refractory Non-Infectious Uveitis: A Proof-of-Concept Study
Status:
Recruiting
Recruiting
Trial end date:
2024-12-30
2024-12-30
Target enrollment:
0
0
Participant gender:
All
All
Summary
The objective of this study is to explore the efficacy of ixekizumab in treating patients with a diagnosis of non-infectious intermediate, posterior, panuveitis, or chronic steroid-dependent anterior uveitis who had failed treatment with a classic synthetic DMARD including methotrexate, mycophenolate, cyclosporin, azathioprine, cyclophosphamide and/or at least one anti-TNF agent including adalimumab, infliximab, etanercept, golimumab or certolizumab.Phase:
Phase 4Accepts Healthy Volunteers?
Accepts Healthy VolunteersDetails
Lead Sponsor:
Massachusetts Eye Research and Surgery InstitutionCollaborator:
Eli Lilly and CompanyTreatments:
Ixekizumab
Criteria
Inclusion Criteria:1. At least 18 years of age
2. Diagnosis of non-infectious intermediate, posterior, panuveitis, or chronic steroid
dependent anterior uveitis
3. Failure of at least one classic synthetic DMARD including Methotrexate, Mycophenolate,
Cyclosporin, Azathioprine, Cyclophosphamide, and/or at least one anti-TNF agent
including Adalimumab, Infliximab, Etanercept, Golimumab or Certolizumab
4. Active disease at screening visit
5. At least 1 of the following parameters in at least one eye:
- active inflammatory chorioretinal and/or inflammatory retinal vascular lesions
- ≥ 1+ vitreous haze (Nussenblatt criteria)
- ≥ 2+ anterior chamber cells (National Eye Institute/Standardization of Uveitis
Nomenclature criteria)
- Cystoid macular edema, seen on optical coherence tomography and/or fluorescein
angiography
- FA leakage pattern deemed by investigators to be suggestive of active
intermediate, posterior, and panuveitis, including optic disc, retinal vascular,
and macular leakages
- Active snowbanking
Exclusion Criteria:
- The presence of only acute anterior uveitis.
- Serpiginous choroidopathy
- Subject with prior inadequate response to high-dose oral corticosteroids (> 60 mg of
prednisone)
- Subject with confirmed or suspected infectious uveitis
- Patients with intraocular pressure of ≥ 25 mmHg or evidence of optic nerve injury
- Corneal or lens opacity that precludes adequate ophthalmic evaluation.
- Patients likely to undergo cataract surgery during the duration of the trial.
- Patients with Best Corrected Visual Acuity (BCVA) less than 20 letters (Early
Treatment Diabetic Retinopathy Study)
- Dose of concomitant immunosuppressive therapy at the baseline visit:
- Methotrexate (MTX) ˃ 25 mg per week
- Cyclosporine ˃ 4 mg/kg per day
- Mycophenolate mofetil ˃ 3 grams per day or an equivalent drug to mycophenolate
mofetil (e.g. mycophenolic acid) at an equivalent dose approved by the medical
monitor.
- Azathioprine ˃ 175 mg per day
- Tacrolimus (oral formulation) > 8 mg per day
- If entering the study on 1 concomitant immunosuppressive therapy, dose has been
increased within the last 28 days prior to Baseline visit.
- Subject has received Retisert® (implant) within 3 years prior to the Baseline visit or
that has had complications related to the device. Subject has had Retisert® (implant)
removed within 90 days prior to the Baseline visit or has had complications related to
the removal of the device
- Subject has received intraocular or periocular corticosteroids within 30 days prior to
Baseline visit
- Subject with proliferative or severe non-proliferative diabetic retinopathy or
clinically significant macular edema due to diabetic retinopathy
- Subject with neovascular/wet age-related macular degeneration
- Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction,
epiretinal membranes, etc.) with the potential for macular structural damage
independent of the inflammatory process, deemed macular pathology is deemed by a
retinal specialist to be a potential cofounder of patient's visual acuity reduction
- Subject with severe vitreous haze that precludes visualization of the fundus at the
baseline visit
- Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the
baseline visit
- Subject has received intravitreal anti-VEGF therapy within 45 days of the Baseline
visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab) or within 60 days of the
Baseline visit for anti-VEGF Trap (aflibercept)
- Subject has received intravitreal methotrexate within 90 days prior to the Baseline
visit
- Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening
visit
- Subject with macular edema as the only sign of uveitis
- Subject with a history of scleritis
- Subject with intolerance to high-dose oral corticosteroids (equivalent of oral
prednisone 1 mg/kg/day or 60 to 80 mg/day)
- Subject on cyclophosphamide within 30 days prior to the Baseline visit
- 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 48 weeks after day 0. This includes both
ocular and non-ocular clinical trials
- Major surgery within 8 weeks prior to screening or planned major surgery within 6
months following randomization
- Treatment with intravenous gamma globulin or plasmapheresis during the course of the
trial
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
- History of severe allergic or anaphylactic reactions to human, humanized monoclonal
antibodies
- Prior history of Crohn's Colitis or Ulcerative Colitis
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary
(including obstructive pulmonary disease), renal, hepatic, endocrine (include
uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated
diverticulitis, liver disease or peptic ulcer disease)
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other infections (including but not limited to tuberculosis and atypical
mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal
infections of nail beds)
- Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening
- Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients
should be screened for latent TB and, if positive, treated following local practice
guidelines prior to initiating trial. Patients treated for tuberculosis with no
recurrence in 3 years are permitted
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of active malignant disease, malignancies diagnosed within the previous 5
years (including hematological malignancies and solid tumors, except basal and
squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
been excised and cured)
- Pregnant women or breast-feeding mothers
- Patients with reproductive potential not willing to use an effective method of
contraception
- History of alcohol, drug, or chemical abuse within 1 year prior to screening.
- Serum creatinine > 1.6 mg/dL (141 μmol/L) in female patients and > 1.9 mg/dL (168
μmol/L) in male patients. Patients with serum creatinine values exceeding limits may
be eligible for the study if their estimated glomerular filtration rates (GFR) are
>30.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper
limit of normal (ULN)
- Total Bilirubin > 1.5 ULN
- Platelet count < 100 x 109/L (100,000/mm3)
- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White Blood Cells < 3.0 x 109/L (3000/mm3)
- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
- Positive Hepatitis BsAg, or Hepatitis C antibody