Safety and Efficacy of AIN457 in Noninfectious Uveitis

NCT00685399 | Completed Phase 2 Results

• 2 other identifiers: CAIN457A22082011-001243-67
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 23

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Responders in Cohort 1, 2, 3 and 6 at Day 57

  Day 1 (Baseline), Day 57

• Number of Complete Responders in Cohort 2, 3 and 6 at Day 57

  Day 1 (Baseline), Day 57

• Number of Participants With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs

  Baseline (Day 1) up to Month 8

• Number of Participants Who Were Able to Induce a Remission in Uveitis

  Day 1 to Day 85

• Number of Participants With Remission in Uveitis

  Baseline (Day 1) up to Month 8

Study Arms (8)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Cohort 3

EXPERIMENTAL

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

Drug: AIN 457

Cohort 4

EXPERIMENTAL

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

Cohort 5

EXPERIMENTAL

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

Cohort 6 Arm 1

EXPERIMENTAL

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

Cohort 6 Arm 2

EXPERIMENTAL

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

Cohort 6 Arm 3

EXPERIMENTAL

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

Interventions

AIN457 DRUG

AIN457 subcutaneous dose

Also known as: Secukinumab

Cohort 1; Cohort 2

AIN 457 DRUG

AIN457 low dose (i.v)

Also known as: Secukinumab

Cohort 3; Cohort 4; Cohort 6 Arm 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Novartis Investigative Site

Beverly Hills, California, 90211, United States

Location

Novartis Investigative Site

Los Angeles, California, 90033, United States

Location

Novartis Investigative Site

Sacramento, California, 95819, United States

Location

Novartis Investigative Site

Denver, Colorado, 80210, United States

Location

Novartis Investigative Site

Golden, Colorado, 80401, United States

Location

Novartis Investigative Site

Littleton, Colorado, 80120, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21201, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21287, United States

Location

Novartis Investigative Site

Cambridge, Massachusetts, 02142, United States

Location

Novartis Investigative Site

Kansas City, Missouri, 64111, United States

Location

Novartis Investigative Site

Teaneck, New Jersey, 07666, United States

Location

Novartis Investigative Site

New York, New York, 10022, United States

Location

Novartis Investigative Site

Slingerlands, New York, 12159, United States

Location

Novartis Investigative Site

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44195, United States

Location

Novartis Investigative Site

Spartanburg, South Carolina, 29306, United States

Location

Novartis Investigative Site

Arlington, Texas, 76012, United States

Location

Novartis Investigative Site

Austin, Texas, 78793, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Heidelberg, 691120, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Related Publications (2)

• 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.

  PMID: 25638011 RESULT

• 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.

  PMID: 20926833 DERIVED

MeSH Terms

Conditions

Uveitis; Behcet Syndrome; Ophthalmia, Sympathetic; Multifocal Choroiditis; Birdshot Chorioretinopathy; Retinal Vasculitis; Sarcoidosis; Uveitis, Intermediate; Panuveitis; Uveitis, Posterior

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases; Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular; Autoimmune Diseases; Immune System Diseases; Choroiditis; Choroid Diseases; White Dot Syndromes; Chorioretinitis; Retinitis; Retinal Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2008
• First Posted: May 28, 2008
• Study Start: June 1, 2008
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 17, 2017
• Results First Posted: July 17, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); DE (3)