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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 )

Tracking Information
First Submitted Date  ICMJE February 1, 2012
First Posted Date  ICMJE February 6, 2012
Results First Submitted Date  ICMJE August 15, 2018
Results First Posted Date  ICMJE October 31, 2018
Last Update Posted Date October 31, 2018
Actual Study Start Date  ICMJE December 20, 2012
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
  • 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
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 3, 2012)
Number of patients with a clinical response rate [ Time Frame: Screening and Day 29 ]
Clinical response rate is defined by any one of the following criteria 1) An improvement of 2 or more steps in vitreous haze, improvement in visual acuity (10 or more letters) or improvement of choroidal neovascular macular edema using dilated ophthalmoscopy and/or fluorescein angiography.
Change History Complete list of historical versions of study NCT01526889 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2012)
  • Change in vitritis [ Time Frame: Baseline, Day 15, 29, 43, 57 and/or 85 ]
    Change in vitritis will be measured using the standardized vitreous haze score (Nussenblatt)
  • Change in visual acuity [ Time Frame: Baseline, Day 15, 29, 43, 57 and/or 85 ]
    Visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions.
  • Number of patients with adverse events [ Time Frame: Day 85 ]
    Adverse events will be determined based on descriptive analyses of vital signs, ECG evaluation, and clinical safety laboratory evaluations.
  • Serum versus time concentrations of LFG316 [ Time Frame: Days1-85 ]
    Blood will be collected at each visit for the determination of drug serum concentrations following the intravitreal doses.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety,Tolerability and Efficacy of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, posterior-or Panuveitis ,
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-infectious Intermediate Uveitis
  • Non-infectious Posterior Uveitis
  • Non-infectious Panuveitis
Intervention  ICMJE
  • Drug: LFG316
    LFG316 administered intravitreally (IVT)
  • Drug: Conventional Therapy
    Conventional Therapy administered in accordance with its prescribing info.
Study Arms  ICMJE
  • Experimental: LFG316 -Intravitreal Injection
    Intervention: Drug: LFG316
  • Active Comparator: Conventional Therapy
    Intervention: Drug: Conventional Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 2, 2018)
25
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2012)
24
Actual Study Completion Date  ICMJE August 24, 2017
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01526889
Other Study ID Numbers  ICMJE CLFG316A2204
2011-003254-90 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP