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Safety and Efficacy of AIN457 in Noninfectious Uveitis

Primary Purpose

Non-infectious Uveitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AIN457
AIN 457
AIN457
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-infectious Uveitis focused on measuring Uveitis, eye, IL-17, IL-17A, IL17, AIN457, Vogt-Koyanagi-Harada, Behcet's, Behcet, Sympathetic ophthalmia, Multifocal choroiditis, Birdshot, HLA-B27, Birdshot retinochoroiditis, Retinal vasculitis, Sarcoidosis, Intermediate uveitis, Panuveitis, Posterior uveitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6 Arm 1

Cohort 6 Arm 2

Cohort 6 Arm 3

Arm Description

Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22.

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.

Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.

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.

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.

Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).

Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.

Full Information

First Posted
May 23, 2008
Last Updated
June 15, 2017
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00685399
Brief Title
Safety and Efficacy of AIN457 in Noninfectious Uveitis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-infectious Uveitis
Keywords
Uveitis, eye, IL-17, IL-17A, IL17, AIN457, Vogt-Koyanagi-Harada, Behcet's, Behcet, Sympathetic ophthalmia, Multifocal choroiditis, Birdshot, HLA-B27, Birdshot retinochoroiditis, Retinal vasculitis, Sarcoidosis, Intermediate uveitis, Panuveitis, Posterior uveitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 6 Arm 1
Arm Type
Experimental
Arm Description
Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).
Arm Title
Cohort 6 Arm 2
Arm Type
Experimental
Arm Description
Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).
Arm Title
Cohort 6 Arm 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AIN457
Other Intervention Name(s)
Secukinumab
Intervention Description
AIN457 subcutaneous dose
Intervention Type
Drug
Intervention Name(s)
AIN 457
Other Intervention Name(s)
Secukinumab
Intervention Description
AIN457 low dose (i.v)
Intervention Type
Drug
Intervention Name(s)
AIN457
Other Intervention Name(s)
Secukinumab
Intervention Description
AIN457 high dose (i.v)
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died
Description
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.
Time Frame
Day 1 to Day 603
Secondary Outcome Measure Information:
Title
Number of Responders in Cohort 1, 2, 3 and 6 at Day 57
Description
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.
Time Frame
Day 1 (Baseline), Day 57
Title
Number of Complete Responders in Cohort 2, 3 and 6 at Day 57
Description
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).
Time Frame
Day 1 (Baseline), Day 57
Title
Number of Participants With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs
Description
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.
Time Frame
Baseline (Day 1) up to Month 8
Title
Number of Participants Who Were Able to Induce a Remission in Uveitis
Description
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.
Time Frame
Day 1 to Day 85
Title
Number of Participants With Remission in Uveitis
Description
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.
Time Frame
Baseline (Day 1) up to Month 8
Title
Number of Participants Who Were Able to Re-induce a Remission if a Flare-up Occurs
Description
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.
Time Frame
Day 1 to Day 57

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Novartis Investigative Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95819
Country
United States
Facility Name
Novartis Investigative Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
Novartis Investigative Site
City
Golden
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
Novartis Investigative Site
City
Littleton
State/Province
Colorado
ZIP/Postal Code
80120
Country
United States
Facility Name
Novartis Investigative Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Novartis Investigative Site
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02142
Country
United States
Facility Name
Novartis Investigative Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Novartis Investigative Site
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Facility Name
Novartis Investigative Site
City
Slingerlands
State/Province
New York
ZIP/Postal Code
12159
Country
United States
Facility Name
Novartis Investigative Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Novartis Investigative Site
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29306
Country
United States
Facility Name
Novartis Investigative Site
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Novartis Investigative Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78793
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
691120
Country
Germany
Facility Name
Novartis Investigative Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25638011
Citation
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.
Results Reference
result
PubMed Identifier
20926833
Citation
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.
Results Reference
derived

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Safety and Efficacy of AIN457 in Noninfectious Uveitis

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