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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-infectious Intermediate Uveitis; Non-infectious Posterior Uveitis; Non-infectious Panuveitis
• Intervention / Treatment: Drug: LFG316; Drug: Conventional Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Novartis Investigative Site
  • London, United Kingdom, EC1V 2PD
    • Novartis Investigative Site
• United States
  • Colorado
    • Golden, Colorado, United States, 80401
      • Novartis Investigative Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Novartis Investigative Site
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02142
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5540
      • Novartis Investigative Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LFG316 -Intravitreal Injection	Drug: LFG316; LFG316 administered intravitreally (IVT)
ACTIVE_COMPARATOR: Conventional Therapy	Drug: Conventional Therapy; Conventional Therapy administered in accordance with its prescribing info.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2012
• Primary Completion (ACTUAL): February 16, 2017
• Study Completion (ACTUAL): August 24, 2017

Study Registration Dates

• First Submitted: February 1, 2012
• First Submitted That Met QC Criteria: February 3, 2012
• First Posted (ESTIMATE): February 6, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Visual acuity; Non-infectious uveitis; Panuveitis; Vitreous Haze; Inflammation of the uvea; inflammation of the middle, pigmented vascular structures of the eye, iris, ciliary body, choroid plexus
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Choroid Diseases; Choroiditis; Uveitis; Uveitis, Posterior; Panuveitis; Uveitis, Intermediate; Pars Planitis
• Other Study ID Numbers: CLFG316A2204; 2011-003254-90 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No