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

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ClinicalTrials.gov Identifier: NCT01526889
Recruitment Status : Completed
First Posted : February 6, 2012
Results First Posted : October 31, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Non-infectious Intermediate Uveitis Non-infectious Posterior Uveitis Non-infectious Panuveitis Drug: LFG316 Drug: Conventional Therapy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 20, 2012
Actual Primary Completion Date : February 16, 2017
Actual Study Completion Date : August 24, 2017


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.




Primary Outcome Measures :
  1. Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye [ Time Frame: Day 85 (end of study) ]

    Response rate as defined by:

    1. An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR
    2. An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR
    3. An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR
    4. Absence of chorioretinal lesions as determined by the investigator

  2. Number of Participants With Remission in Study Eye - Treatment Period [ Time Frame: Day 85 (end of study) ]

    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.


Secondary Outcome Measures :
  1. Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period [ Time Frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) ]

    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.


  2. Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period [ Time Frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) ]

    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.


  3. Number of Patients With Macular Edema in Study Eye - Treatment Period [ Time Frame: Day 85 (end of study) ]
    Macular edema is a sign of uveitis.

  4. Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period [ Time Frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) ]
    Chorioretinal lesions is a sign of uveitis.

  5. Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period [ Time Frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) ]
    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).

  6. Number of Participants With or Without Anti-LFG316 Antibodies [ Time Frame: Throughout the study (treatment and extension period), up to day 271 ]

    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.


  7. Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period [ Time Frame: Day 2, 15, 29, 43, 57 and, 85 (end of the study) ]
    Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01526889


Locations
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United States, Colorado
Novartis Investigative Site
Golden, Colorado, United States, 80401
United States, Georgia
Novartis Investigative Site
Marietta, Georgia, United States, 30060
United States, Massachusetts
Novartis Investigative Site
Cambridge, Massachusetts, United States, 02142
United States, Nebraska
Novartis Investigative Site
Omaha, Nebraska, United States, 68198-5540
United States, New Jersey
Novartis Investigative Site
Teaneck, New Jersey, United States, 07666
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
United Kingdom
Novartis Investigative Site
Bristol, United Kingdom, BS1 2LX
Novartis Investigative Site
London, United Kingdom, EC1V 2PD
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] August 28, 2017
Study Protocol  [PDF] September 7, 2015


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01526889     History of Changes
Other Study ID Numbers: CLFG316A2204
2011-003254-90 ( EudraCT Number )
First Posted: February 6, 2012    Key Record Dates
Results First Posted: October 31, 2018
Last Update Posted: October 31, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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

Additional relevant MeSH terms:
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Uveitis
Panuveitis
Uveitis, Posterior
Uveitis, Intermediate
Pars Planitis
Uveal Diseases
Eye Diseases
Choroiditis
Choroid Diseases