This study was performed to evaluate the efficacy and safety of AIN457 for patients with
active uveitis that requires systemic immunosuppression.

Safety and Efficacy of AIN457 in Noninfectious Uveitis

Non-infectious Uveitis

AIN457

AIN 457

An Open-label Proof-of-concept Study With a Double-masked, Dose-ranging Component to Assess the Effects of AIN457 in Patients With Noninfectious Uveitis

AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an
abnormal laboratory finding), syndrome or disease which either occurs during study,
having been absent at baseline, or, if present at baseline, appears to worsen. Serious
adverse events are any untoward medical occurrences that result in death, are life
threatening, require (or prolong) hospitalization, cause persistent or significant
disability/incapacity, result in congenital anomalies or birth defects, or are other
conditions which in judgment of investigators represent significant hazards.

A "responder" was defined as a participant who fulfilled at least one of the 3 criteria
compared to baseline: 1. Increase in visual acuity by at least 15 letters using Early
Treatment Diabetic Retinopathy Study method, no increase in daily prednisone dose
compared to week 1 and without worsening of uveitis. 2. Decrease in vitreous haze by 2
steps or more or for participants with anterior uveitis, resolution of the anterior
chamber inflammation (i.e., no cells or only a rare cell in the anterior chamber (score 0
or trace (0.5+)), use measurement before dilation), no increase in daily prednisone dose
compared to week 1 and without any worsening of uveitis.3 For those participant on a. >20
mg/day of prednisone during week 1: Reduction in daily prednisone dose to 10 mg/day or
less. b. ≤20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 0
mg/day. c. topical corticosteroids during week 1: Reduction in daily topical
corticosteroid dose to 0 during the last 2 weeks.

A "complete responder" was defined as a participant who was able to stop all topical and
systemic corticosteroids in both eyes and maintain remission of uveitis (=remains a
responder as defined above) lasting at least 1 week (since stopping corticosteroids, if
corticosteroids were given).

Participants intake of oral prednisone or topical corticosteroid and other
immunosuppressant drugs was reduced if participant was on up to 1.5 mg/kg/day dose of
prednisone during the week prior to Day 1 or whom the resumption of prednisone was not
considered the appropriate systemic therapy by investigator or who have never been on
systemic immunosuppressive therapy and whose uveitis was so severe that, in the
clinician's judgment, prednisone at a dose of 1.0-1.5 mg/kg/day alone will be
insufficient to control the uveitis or participant with HLA-B27-associated anterior
uveitis who would ordinarily be started on systemic prednisone. The analysis was not
conducted due to small sample size, insufficient number of participants and low initial
doses; limited conclusions were drawn about dose response relationship leading to non
summarization of results.

Participants with uveitis who were able to stop all topical and systemic topical
corticosteroids in both eyes by Day 57 visit after the first course of one or two doses
of AIN457 were to be categorized as nonresponders and were to be discontinued from the
study at the Day 85 visit. The analysis was not conducted due to small sample size,
insufficient number of participants and low initial doses; limited conclusions were drawn
about dose response relationship leading to non summarization of results.

Participants with uveitis who were able to stop all topical and systemic topical
corticosteroids in both eyes after the first course of one or two doses by Day 57 visit .
The analysis was not conducted due to small sample size, insufficient number of
participants and low initial doses; limited conclusions were drawn about dose response
relationship leading to non summarization of results.

A flare was defined as an increase of inflammation in either eye so that the anterior
chamber cell score or the vitreous haze score become 1+ or greater. Vitreous haze was
evaluated with an indirect ophthalmoscope and a hand-held 20-diopter lens. Haze is
defined as a reduction in the clarity of fundus details seen through the vitreous, the
degree of haze was quantified using standard National Eye Institute (NEI) photographs.
The standard photographs provide a grading scale with photographs of fundi with vitreous
haze grades "0" (zero), "trace" (which counts as 0.5+), 1+, 2+, 3+, and 4+. If the amount
of vitreous haze appears to fall between two integer grades, the value would be recorded
as halfway between the grades. The analysis was not conducted due to small sample size,
insufficient number of participants and low initial doses; limited conclusions were drawn
about dose response relationship leading to non summarization of results.

Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram
(mg/kg) intravenous (i.v.) dose on Day 1 and Day 22.

Participants were administered with AIN457 (Sp2/0 or Chinese hamster ovary cell (CHO)
derived) 10 mg/kg, (CHO derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and
if needed a second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3
participants from cohort 1 rolled on into this cohort.

Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.

Extension period: Participants were administered with AIN457 10 mg/kg, i.v. (with or
without a short course of corticosteroids) once a flare had occurred, or periodically at
a frequency of not more than once per month at the discretion of the investigator.

Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was
given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well
tolerated by all.

Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v.
infusion every two weeks (Days 1, 15, 29, and 43).

Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every
two weeks (Days 1, 15, 29, and 43).

Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every
4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15
and 43 to maintain masking of treatment groups.

Safety and Efficacy of AIN457 in Noninfectious Uveitis

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status