Safety and Efficacy of AIN457 in Noninfectious Uveitis

An Open-label Proof-of-concept Study With a Double-masked, Dose-ranging Component to Assess the Effects of AIN457 in Patients With Noninfectious Uveitis

This study was performed to evaluate the efficacy and safety of AIN457 for patients with active uveitis that requires systemic immunosuppression.

Study Overview

• Status: Completed
• Conditions: Non-infectious Uveitis
• Intervention / Treatment: Drug: AIN457; Drug: AIN457; Drug: AIN 457

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Heidelberg, Germany, 691120
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90033
      • Novartis Investigative Site
    • Sacramento, California, United States, 95819
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • Novartis Investigative Site
    • Golden, Colorado, United States, 80401
      • Novartis Investigative Site
    • Littleton, Colorado, United States, 80120
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Novartis Investigative Site
    • Baltimore, Maryland, United States, 21287
      • Novartis Investigative Site
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02142
      • Novartis Investigative Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Novartis Investigative Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10022
      • Novartis Investigative Site
    • Slingerlands, New York, United States, 12159
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Novartis Investigative Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306
      • Novartis Investigative Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Novartis Investigative Site
    • Austin, Texas, United States, 78793
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Active uveitis (i.e., uveitis that is not in remission).
• Intermediate uveitis, posterior uveitis, or panuveitis must be sufficiently severe that systemic immunosuppression is indicated.

Exclusion criteria:

• Active infection.
• Weight must not be greater that 120kg.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22.	Drug: AIN457; AIN457 subcutaneous dose; Other Names: Secukinumab; Drug: AIN457; AIN457 high dose (i.v); Other Names: Secukinumab
Experimental: Cohort 2; Participants were administered with AIN457 (Sp2/0 or Chinese hamster ovary cell (CHO) derived) 10 mg/kg, (CHO derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed a second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort.	Drug: AIN457; AIN457 subcutaneous dose; Other Names: Secukinumab; Drug: AIN457; AIN457 high dose (i.v); Other Names: Secukinumab
Experimental: Cohort 3; Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.	Drug: AIN 457; AIN457 low dose (i.v); Other Names: Secukinumab
Experimental: Cohort 4; Extension period: Participants were administered with AIN457 10 mg/kg, i.v. (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator.	Drug: AIN 457; AIN457 low dose (i.v); Other Names: Secukinumab
Experimental: Cohort 5; Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all.	Drug: AIN457; AIN457 subcutaneous dose; Other Names: Secukinumab; Drug: AIN457; AIN457 high dose (i.v); Other Names: Secukinumab
Experimental: Cohort 6 Arm 1; Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).	Drug: AIN457; AIN457 subcutaneous dose; Other Names: Secukinumab; Drug: AIN457; AIN457 high dose (i.v); Other Names: Secukinumab
Experimental: Cohort 6 Arm 2; Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).	Drug: AIN 457; AIN457 low dose (i.v); Other Names: Secukinumab
Experimental: Cohort 6 Arm 3; Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.	Drug: AIN457; AIN457 subcutaneous dose; Other Names: Secukinumab; Drug: AIN457; AIN457 high dose (i.v); Other Names: Secukinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died	AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	Day 1 to Day 603

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Responders in Cohort 1, 2, 3 and 6 at Day 57	A "responder" was defined as a participant who fulfilled at least one of the 3 criteria compared to baseline: 1. Increase in visual acuity by at least 15 letters using Early Treatment Diabetic Retinopathy Study method, no increase in daily prednisone dose compared to week 1 and without worsening of uveitis. 2. Decrease in vitreous haze by 2 steps or more or for participants with anterior uveitis, resolution of the anterior chamber inflammation (i.e., no cells or only a rare cell in the anterior chamber (score 0 or trace (0.5+)), use measurement before dilation), no increase in daily prednisone dose compared to week 1 and without any worsening of uveitis.3 For those participant on a. >20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 10 mg/day or less. b. ≤20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 0 mg/day. c. topical corticosteroids during week 1: Reduction in daily topical corticosteroid dose to 0 during the last 2 weeks.	Day 1 (Baseline), Day 57
Number of Complete Responders in Cohort 2, 3 and 6 at Day 57	A "complete responder" was defined as a participant who was able to stop all topical and systemic corticosteroids in both eyes and maintain remission of uveitis (=remains a responder as defined above) lasting at least 1 week (since stopping corticosteroids, if corticosteroids were given).	Day 1 (Baseline), Day 57
Number of Participants With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs	Participants intake of oral prednisone or topical corticosteroid and other immunosuppressant drugs was reduced if participant was on up to 1.5 mg/kg/day dose of prednisone during the week prior to Day 1 or whom the resumption of prednisone was not considered the appropriate systemic therapy by investigator or who have never been on systemic immunosuppressive therapy and whose uveitis was so severe that, in the clinician's judgment, prednisone at a dose of 1.0-1.5 mg/kg/day alone will be insufficient to control the uveitis or participant with HLA-B27-associated anterior uveitis who would ordinarily be started on systemic prednisone. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.	Baseline (Day 1) up to Month 8
Number of Participants Who Were Able to Induce a Remission in Uveitis	Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes by Day 57 visit after the first course of one or two doses of AIN457 were to be categorized as nonresponders and were to be discontinued from the study at the Day 85 visit. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.	Day 1 to Day 85
Number of Participants With Remission in Uveitis	Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes after the first course of one or two doses by Day 57 visit . The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.	Baseline (Day 1) up to Month 8
Number of Participants Who Were Able to Re-induce a Remission if a Flare-up Occurs	A flare was defined as an increase of inflammation in either eye so that the anterior chamber cell score or the vitreous haze score become 1+ or greater. Vitreous haze was evaluated with an indirect ophthalmoscope and a hand-held 20-diopter lens. Haze is defined as a reduction in the clarity of fundus details seen through the vitreous, the degree of haze was quantified using standard National Eye Institute (NEI) photographs. The standard photographs provide a grading scale with photographs of fundi with vitreous haze grades "0" (zero), "trace" (which counts as 0.5+), 1+, 2+, 3+, and 4+. If the amount of vitreous haze appears to fall between two integer grades, the value would be recorded as halfway between the grades. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.	Day 1 to Day 57

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Letko E, Yeh S, Foster CS, Pleyer U, Brigell M, Grosskreutz CL; AIN457A2208 Study Group. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology. 2015 May;122(5):939-48. doi: 10.1016/j.ophtha.2014.12.033. Epub 2015 Jan 29.
• Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group, Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group, Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010 Oct 6;2(52):52ra72. doi: 10.1126/scitranslmed.3001107.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: May 23, 2008
• First Submitted That Met QC Criteria: May 27, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Uveitis; Sarcoidosis; eye; Retinal vasculitis; IL-17; AIN457; HLA-B27; Panuveitis; IL-17A; IL17; Vogt-Koyanagi-Harada; Behcet's; Behcet; Sympathetic ophthalmia; Multifocal choroiditis; Birdshot; Birdshot retinochoroiditis; Intermediate uveitis; Posterior uveitis
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A2208; 2011-001243-67 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No