Clinical trial NCT01526889: Safety,Tolerability and Efficacy of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, posterior-or Panuveitis ,
Official title: A Randomized, Active-controlled, Open-label, Multicenter proof-of Concept Study of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, Posterior-, or Panuveitis Requiring Systemic Immunosuppressive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-infectious Intermediate Uveitis
Non-infectious Posterior Uveitis
Non-infectious Panuveitis
Keywords: Non-infectious uveitis
Panuveitis
Visual acuity
Vitreous Haze
Inflammation of the uvea
inflammation of the middle, pigmented vascular structures of the eye, iris, ciliary body, choroid plexus
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-02-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a multi-center, randomized, active-controlled, open-label study. Approximately 24 patients with active, non-infectious intermediate-, posterior-, or panuveitis requiring systemic immunosuppressive therapy were enrolled.

Safety, efficacy, and PK assessments occurred at scheduled visits over a 12-week period. Low-molecular-weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses for which might have changed.

Patients responding to treatment were offered up to 6 months of extended treatment. Assessments for safety included laboratory safety tests, ECGs, physical exams, ocular exams, vital signs and the monitoring of adverse events. Study participation varied from a minimum of 3 months to a maximum of 9 months.

Detailed description: Approximately 24 patients with active non-infectious uveitis, in at least one eye, requiring intensification of systemic immunosuppressive therapy were enrolled and randomized to receive intravitreal LFG316 or conventional therapy (investigator's discretion). Only one eye (the study eye) were treated with LFG316 and the other eye (fellow eye) were treated at the investigator's discretion.Throughout the study, the fellow eye might have been treated as needed; except that certain systemic medications were prohibited. There was 1 screening and 8 scheduled visits over 85 days for a total of 9 site visits for all patients.

At Day 85, patients receiving LFG316 treatment who met the criteria for a 'responder', were offered an additional 6 months of LFG316 treatment on a PRN basis. Additional 3 scheduled visits were attended by LFG316-responder patients during the extension period. However, patients could have unscheduled visits as needed and as determined by the investigator. Safety evaluation and ocular assessments were performed throughout the study duration. Patients in the treatment extension phase, who experienced a flare post their last dose and required treatment, might have received a dose of LFG316. These patients were assessed for a response at their next PRN visit as scheduled by the investigator. Visit frequency was determined by the investigator. If they continued to respond to LFG316 therapy, they might have remained in the PRN treatment arm. They might have received up to 7 additional doses of LFG316 in the PRN period. Throughout the trial LFG316 were not administered more frequently than monthly. Patients in the extension phase, who discontinued treatment prematurely were asked to return approximately 1 month after their last dose. Low molecular weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses which might have changed.

Eligibility criteria: Key Inclusion Criteria:

* Male or female patients 18 years or older
* Active NIU, in at least one eye, as defined below, in patients requiring intensification of systemic immunosuppressive therapy;
* Vitreous haze at least 1+ on the scale of Nussenblatt et al 1985,or
* Chorioretinal lesions due to uveitis (chorioretinal lesions due to infectious uveitis excluded)
* Patients with a flare and at the time of the enrollment on systemic corticosteroid or non-steroidal immunosuppressants had their therapy tapered or stopped, respectively, at the time of intravitreal LFG316 administration.

Visual acuity (ETDRS method) of 20 letters (20/400 Snellen equivalent) or better in the study eye.

* For female patients, must not be pregnant or lactating and must, unless post-menopausal, use effective contraception.
* Ability to provide informed consent and comply with the protocol.

Key Exclusion Criteria:

* Uveitis so severe that, in the investigator's judgment, it was too risky to test an experimental drug
* Any biologic immunosuppressive agent given via intravitreal, intravenous or subcutaneous route within 4-12 months depending on the agent.
* History of infectious uveitis or endophthalmitis in either eye.
* History of retinal detachment
* Any intraocular surgery, intravitreal injection, periocular injection, or laser photocoagulation to the study eye within 90 days prior to dosing.
* In the study eye, cataract expected to interfere with study conduct or require surgery during the study.
* Forms of uveitis that may have spontaneously resolved

Primary outcomes:
measure: Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye
timeFrame: Day 85 (end of study)
measure: Number of Participants With Remission in Study Eye - Treatment Period
timeFrame: Day 85 (end of study)
Secondary outcomes:
measure: Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period
timeFrame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
measure: Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period
timeFrame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
measure: Number of Patients With Macular Edema in Study Eye - Treatment Period
timeFrame: Day 85 (end of study)
measure: Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period
timeFrame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
measure: Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period
timeFrame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
measure: Number of Participants With or Without Anti-LFG316 Antibodies
timeFrame: Throughout the study (treatment and extension period), up to day 271
measure: Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period
timeFrame: Day 2, 15, 29, 43, 57 and, 85 (end of the study)
Other outcomes:
Locations:
city: Golden
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Cambridge
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Teaneck
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: