Safety,Tolerability and Efficacy of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, posterior-or Panuveitis ,

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non-infectious Intermediate Uveitis, Non-infectious Posterior Uveitis, Non-infectious Panuveitis

Intervention / Treatment
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* Drug: LFG316
* Drug: Conventional Therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFG316 -Intravitreal Injection<br> | Drug: LFG316<br>* LFG316 administered intravitreally (IVT)<br>|
| Active Comparator: Conventional Therapy<br> | Drug: Conventional Therapy<br>* Conventional Therapy administered in accordance with its prescribing info.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye | Response rate as defined by: An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR Absence of chorioretinal lesions as determined by the investigator | Day 85 (end of study) | 
| Number of Participants With Remission in Study Eye - Treatment Period | Remission (complete response) was defined as any patient who had: a vitreous haze score of 0 or 0.5 (scale of 0 to 4) in the study eye, AND an anterior chamber cell score of 0 (scale of 0 to 4), AND no chorioretinal lesions in the study eye, AND was off all immune modulatory therapy (systemic, corticosteroids and topical), AND without any worsening of uveitis during the trial. | Day 85 (end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period | Vitreous haze score (based on funduscopic exam): 0, 0.5/Trace, 1+, 2+, 3+, 4+ Vitreous haze score (scale of 0 to 4) with a score of 4 being the most hazed. | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) | 
| Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period | Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions. ETDRS best-corrected visual acuity was obtained in each eye separately under certified ETDRS conditions. This assessment was to be performed prior to pupil dilation. The number of letters read correctly (for each eye) was recorded. BCVA is based on the number of letters read correctly. | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) | 
| Number of Patients With Macular Edema in Study Eye - Treatment Period | Macular edema is a sign of uveitis. | Day 85 (end of study) | 
| Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period | Chorioretinal lesions is a sign of uveitis. | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) | 
| Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period | anterior chamber cells score (ACCS) with the scores being 0 (≤ 1 cell), 0.5 (1 to 5 aqueous cells), 1 (6 to 15 aqueous cells), 2 (16 to 25 aqueous cells), 3 (26 to 50 aqueous cells), 4 (>50 aqueous cells). | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) | 
| Number of Participants With or Without Anti-LFG316 Antibodies | Blood will be collected at each visit for the profiling of serum drug concentrations. The summary of immunogenicity (IG) by visit . The immunogenicity data (presence/absence of anti-LFG316 antibodies [anti-drug antibodies]). NO: No immunogenicity; YES: Positive immunogenicity. | Throughout the study (treatment and extension period), up to day 271 | 
| Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period | Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations. | Day 2, 15, 29, 43, 57 and, 85 (end of the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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