TerminatedNCT01095250INSUREUpdated Nov 3, 2015Results posted

Safety and Efficacy of AIN457 in Patients With Active Non-infectious Uveitis

A Phase 3 interventional study of AIN457 and AIN457 in Uveitis, sponsored by Novartis Pharmaceuticals. Terminated at 36 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-11-03.

Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment

Why this study was terminated

Terminated: Study in Behcet's disease with mostly active uveitis did not meet its primary endpoint.

Phase: Phase 3
Study type: Interventional
Enrollment: 30
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

This study will assess the safety and efficacy of AIN457 as adjunctive therapy for the treatment of intermediate uveitis, posterior uveitis, or panuveitis requiring systemic immunosuppression.

Conditions studied

Uveitis

Browse trials for

Uveitis 335

Keywords

Active uveitis
intermediate uveitis
panuveitis
posterior uveitis
uveitis

In context

Uveitis

335 studies on the registry are indexed under Uveitis; 37 are open to participants now.

This study's enrollment of 30 is close to the median of 30 across 208 interventional studies indexed under Uveitis.

Browse Uveitis studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male and female subjects ≥18 years of age. Where relevant, parents will also sign the informed consent according to local laws and regulations
Patients with diagnosis of chronic non-infectious intermediate uveitis, posterior uveitis or panuveitis in at least one eye
Evidence of active intermediate, posterior or panuveitis (grade ≥ 2+ vitreous haze with or without the presence of anterior chamber cells) at screening and baseline in at least one eye
Requirement for any of the following immunosuppressive therapies for the treatment or prevention of uveitis:
Prednisone or equivalent ≥10 mg daily at any time within the past 3 months.
≥1 periocular injection or ≥1 intravitreal corticosteroid injection (e.g. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening).
Treatment with either cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate at any time within the past 3 months (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study).
Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator.
Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed

Exclusion criteria

Exclusion Criteria:

Ocular concomitant conditions/disease

Patients receiving or that may require prednisone (or equivalent) ≥1.5 mg/kg/day for the treatment of their active uveitis
Patients with a primary diagnosis of Behcet's disease, anterior uveitis or any intermediate uveitis, posterior uveitis or panuveitis in which the manifestation(s) of the active intraocular inflammatory disease may spontaneously resolve or that are not characterized by the presence of either anterior chamber cells or vitritis (vitreous cell and haze) such as the white dot retino-choroidopathies (i.e. Punctate inner choroidopathy (PIC), acute zonal occult outer retinopathy (AZOOR)
Patients with infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated (e.g. ocular lymphoma)

Ocular treatments

Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening
Treatment with fluocinolone acetonide implant in the study eye within the last 3 years, or dexamethasone intravitreal implant and any other investigational corticosteroid implants in the study eye within the last 6 months.
Intraocular surgery or laser photocoagulation in the study eye within the last 6 weeks prior to screening except for a diagnostic vitreous or aqueous tap with a small-gauge needle
Ocular disease that would interfere with ocular evaluations (e.g. corneal scarring, cataract, vitreous hemorrhage) or that in the opinion of the investigator would complicate the evaluation of the safety or efficacy of the study treatment (e.g. uncontrolled glaucoma, toxoplasma scar, macular scarring)
Current use of or likely need for systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine, ethambutol, etc.)

Systemic conditions or treatments

Any previous treatment with AIN457
Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening. No biologic therapy other than the investigational study treatment will be allowed during the course of the clinical trial
Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil) within the past 5 years prior to screening
Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster or measles) within 2 months prior to screening. No treatment with live or live-attenuated vaccines will be allowed during the course of the clinical trial

Other protocol-defined inclusion/exclusion criteria may apply

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 30 participants (actual)

Study arms

Experimental
AIN457 300mg s.c every 2 weeks
AIN457 300 mg s.c. at baseline, Week 1 and Week 2, then every 2 weeks.
Drug: AIN457
Experimental
AIN457 300mg s.c. every 4 weeks
AIN457 300 mg s.c. at baseline and Week 2, then every 4 weeks.
Drug: AIN457
Experimental
AIN457 150mg s.c every 4 weeks
AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks
Drug: AIN457
Placebo comparator
Placebo s.c every 2 weeks
Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks
Drug: Placebo

Interventions

DrugAIN457
DrugAIN457
DrugAIN457
DrugPlacebo

What researchers measure

Primary outcomes

Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks

Secondary outcomes

Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Change From Baseline in Quality of Life/Patient Reported Outcome Assessments
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Change in Immunosuppressive Medication Score From Baseline to Week 28
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks

Results

Posted Nov 3, 2015

Limitations and caveats

Study CAIN457C2302 was terminated to avoid continuing patients on a study with a low probability of success. Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

Participant flow

Disposition of the 31 randomized patients is summarized in the table below. As a consequence of the early termination, few patients (N=31) were randomized into this study. Of these, 30 patients were discontinued due to administrative reasons (30 patients due to study termination and also one due to misrandomization). One patient withdrew consent.

Participant flow — Overall Study
Milestone	AIN457 300mg s.c Every 2 Weeks	AIN457 300mg s.c. Every 4 Weeks	AIN457 150mg s.c Every 4 Weeks	Placebo s.c Every 2 Weeks
Started	8	10	8	5
Completed	0	0	0	0
Not completed	8	10	8	5
Withdrew: Administrative reasons	8	10	7	5
Withdrew: Withdrawal by subject	0	0	1	0

Outcome measures

PrimaryMean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.

No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.

Time frame:: baseline to 28 weeks