A Multicenter Phase 2 Single-arm Proof-of-concept Trial to Assess the Efficacy and Safety of Ustekinumab in Association With Prednisone for the Treatment of Non-infectious Severe Uveitis (NISU) (USTEKINISU)

This is an interventional treatment trial for Patients With Newly Diagnosed Active NISU Read More

Inclusion criteria:

• Patients with newly diagnosed active NISU: evidence of activity within the 3 months prior to the screening visit as per:

  • VH (visual haze) ≥ 4 on the Miami 9-step scale (or VH >1+ according to SUN classification)
  • and/or macular edema on OCT (Central retinal thickness ≥ 300 microns)
  • and/or other signs of intraocular inflammation (e.g. perivascular sheathing of retinal vessels or leakage of retinal vessels on fluorescein angiography (FA)).
• Patients judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening.

• For men and women of childbearing age, effective contraception must be used by the patient and/or his/her partner throughout the duration of treatment with ustekinumab and until 23 weeks after the end of treatment. Breastfeeding is allowed 23 weeks after the end of treatment. Women considered without risk of pregnancy are those with :

  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system ( IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • sexual abstinence
  • or those surgically sterile (bilateral oophorectomy or hysterectomy).
  • or at least one year of menopause (amenorrhea for at least 12 months)
• Patients over 18 years of age
• Affiliation to a the French health insurance system
• Patients who have given their consent

Exclusion criteria:

• Surgery scheduled within 12 months
• Patients with dementia
• Non-compliant patients
• Weight <45 kg or > 100 kg
• Patients under ward of court, tutelage or legal guardianship
• Pregnant or breast-feeding women

Exclusion criteria related to uveitis:

• Infectious uveitis, masquerade syndromes, or uveitis due to causes other than non-infectious uveitis disease (idiopathic uveitis is permitted)
• Isolated anterior uveitis
• Presence of cataract or posterior capsular opacification so severe that an assessment of the posterior segment of either eye is inadequate or impossible
• Contraindication to mydriasis in either eye or presence of posterior synechiae in the study eye such that mydriasis is inadequate for posterior segment examination
• Intraocular pressure ≥ 25mmHg by Goldmann tonometry or advanced glaucoma (e.g., cup-to-disc ratio > 0.9, split fixation on visual field, or need for > 3 intraocular pressure lowering medications to keep IOP < 22 mmHg) in either eye
• Monocular patient
• Sarcoidosis-related uveitis

Exclusion criteria related to ustekinumab:

• History of congenital or acquired immunodeficiency (e.g. common variable immunodeficiency disease).
• History of prior treatment with ustekinumab
• Hypersensitivity to ustekinumab, one of its excipients or another human or murine monoclonal antibody or latex
• Evidence of active infection at the time of baseline visit, or other Infectious contraindication to ustekinumab
• Neoplasia < 5 years, (except for in situ cervical cancer and skin carcinoma with R0 resection)
• Active tuberculosis or sign of latent tuberculosis (based on a history of untreated contact, a history of opacity of more than 1 cm in diameter on the chest x-ray, or an in vitro test positive[Quantiferon® or T-spot-TB®]). A history of TB disease or latent TB whose treatment was completed is not an exclusion criteria, regardless the Quantiferon® or T-spot-TB® is positive or not.
• Known positive laboratory test for syphilis serology, HIV antibody, hepatitis B surface antigen or anti-nucleocapsid antibody of hepatitis B virus, and/or hepatitis C antibody.
• History of multiple sclerosis and/or other demyelinating disorders
• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.

• Screening laboratory and other analyses showing any of the following abnormal results:

  • AST, ALT > 1.75 × upper limit of the reference range;
  • WBC count < 3.0 × 109/L;

Other treatments:

• Corticosteroids

  • History of ≥3 systemic corticosteroid therapies (topical or inhaled treatments allowed) for another disease (e.g. asthma) within the last 6 months before screening visit
  • Dexamethasone intravitreal implant less than 6 months prior to study

• Patients receiving (or having stopped for less than 6 months or 5 elimination half-lives) an immunosuppressive or immunomodulatory drug or biotherapy:

  • anti TNF-α,
  • tocilizumab,
  • abatacept,
  • anakinra,
  • methotrexate,
  • azathioprine,
  • ciclosporine,
  • cyclophosphamide,
  • dapsone
  • or corticosteroid pulses
• Live vaccine administered within 30 days preceding inclusion
• Hypersensibility to fluorescein and indocyanin green