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)

Who is this study for? Patients with Non-Infectious Severe Uveitis
Status: Recruiting
Location: See all (2) locations...
Intervention Type: Drug, Biological, Other
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

Uveitis is characterized by inflammation of the uvea, which is the middle portion of the eye. The greatest challenge for the treatment of uveitis is patients who have inflammation involving the posterior segment, either primarily in the vitreous (intermediate uveitis), the choroid or retina (posterior uveitis), or involving the entire eye (panuveitis). The term uveitis denotes a heterogeneous collection of diseases including infections, systemic immune-mediated diseases like sarcoidosis, and immune-mediated syndromes confined to the eye like sympathetic ophthalmia. Despite the progress in recent decades, uveitis and the related intraocular inflammation are comparable to diabetes or macular degeneration as a cause of lost quality-adjusted life years due to visual morbidity, and as such are a significant public health problem. The Standardization of Uveitis Nomenclature Working Group Guidelines recommend the use of corticosteroids as the first-line therapy for patients with active uveitis. However, long-term corticosteroid treatment can cause serious systemic and ocular side effects, such as hypertension, diabetes, osteoporosis, cataract, and glaucoma that limit its use in the treatment of uveitis. Alternatively, immunomodulatory therapy (IMT) drugs are given as steroid-sparing agents and have shown good clinical results for both systemic diseases and ocular inflammatory diseases. Given the side effects of chronic corticosteroid therapy and better understanding of the mechanisms of autoimmune-mediated uveitis, the aim of the treatment for patients with noninfectious uveitis is steroid-free remission with IMT. While uveitis is a heterogeneous disease with polygenic and environmental factors, most forms of immune-mediated uveitis are thought to be due to an imbalance between regulatory mechanisms that inhibit the immune system and inflammatory mechanisms, which have evolved to rid the body of infectious organisms, but which can result in immune-mediated, often chronic disease if they are activated outside the context of the immediate infection. The pathophysiology of non-infectious uveitis involves the rupture of peripheral tolerance, resulting in auto-aggressive Th1 or Th17 lymphocytes reaching the eye. L-12 and IL-23 are two key cytokines involved in Th1 and Th17 polarization in uveitis, respectively. Furthermore, these two cytokines share a common subunit (p40). Ustekinumab, a humanized anti-p40 monoclonal antibody, is able to target both IL-12 and IL-23 pathways, thus disrupting Th1 and Th17 immune responses. Decreasing the dose as well as the duration of treatment with GC is of particular importance in uveitis, and ustekinumab, which selectively inhibits Th1 and Th17 pathways in the inflammatory cascade, could provide a ideal additional therapy for non-infectious severe uveitis (NISU) to reach this objective. Therefore, in the present study, we propose to evaluate the efficacy and safety of ustekinumab for the treatment of NISU.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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

Locations
Other Locations
France
CH Avignon
Recruiting
Avignon
CHU Dijon Bourgogne
Recruiting
Dijon
Contact Information
Primary
Philip Bielefeld
bielefeldphilip@gmail.com
0629470887
Time Frame
Start Date: August 1, 2019
Estimated Completion Date: January 2025
Participants
Target number of participants: 29
Treatments
Experimental: Patients
Sponsors
Leads: Centre Hospitalier Universitaire Dijon

This content was sourced from clinicaltrials.gov

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