Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis

Uveitis Clinical Trial

— SARILNIUSATURN  

Official title:

A Randomized, Double-Masked and Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sarilumab Administered Subcutaneously Every 2 Weeks in Patients With Non-Infectious, Intermediate, Posterior or Pan-Uveitis (NIU)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01900431
• Other study ID #: ACT13480
• Secondary ID: 2012-004845-34U1
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2013
• Last updated: April 26, 2016
• Start date: October 2013
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To evaluate the efficacy of sarilumab at week 16 in patients with non-infectious uveitis (NIU).

Secondary Objectives:

To evaluate the change in best corrected visual acuity (BCVA). To evaluate the safety of subcutaneous sarilumab in patients with NIU. To evaluate the change in macular edema. To evaluate the change in other signs of ocular inflammation. To evaluate the effect on retinal vessel leakage. To evaluate the effect of sarilumab on reducing concomitant immunosuppressant therapy.

To evaluate the change in ocular inflammation in the anterior chamber. To evaluate the pharmacokinetics of sarilumab in NIU patients. To evaluate the immunogenicity with anti-drug antibodies (ADA).

Description:

The total duration per patient is up to 58 weeks, which includes a 2 week screening period, 16 weeks principal treatment period, 34 weeks extension treatment period (or open label treatment period), and 6 weeks after last treatment administration.

Non-responder patients, observed within the first 16 weeks, will be offered to be treated by open-label sarilumab. Patients will be treated for 34 extra weeks (up to 18 extra injections).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: April 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

=18 years of age. Non-infectious intermediate-, posterior-, or pan-uveitis in the study eye. Active disease at screening or evidence of activity within the 3 months prior to screening visit. Following the approval of Amendment 2, only patients with "active disease" as defined above will be enrolled in the study.

Starting oral prednisone dose must be greater than or equal to 15 mg/day and less than 80 mg/day.

At screening, patients must be receiving oral prednisone (=15 mg and < 80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with Methotrexate (MTX) (= 25 mg/week) orally or intravenously or intra muscular or subcutaneous). Patients can be receiving one or several of the following therapies: Azathioprine (=2.5 mg/kg/day), Mycophenolate mofetil (=2g daily, orally), Cyclosporine (=4 mg/kg daily, orally), Tacrolimus (=4 mg daily, orally).

The doses may not have been increased for at least 4 weeks prior to the randomization visit.

At randomization, patients have been receiving oral prednisone (=15 mg and < 80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with methotrexate (MTX) (= 25 mg/week) orally or intravenously or intra muscular or subcutaneous).

Azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus have to be permanently discontinued at least 48 hours prior to the first study treatment injection, or longer as per Investigator's judgment. These immunomodulatory therapy (IMTs) are not permitted anytime during the treatment period.

Signed written informed consent.

Exclusion criteria:

Patient with best-corrected visual acuity worse than 20 ETDRS letters in at least one eye.

Patient with confirmed or suspected uveitis of infectious etiology or uveitis of traumatic etiology.

Patient with primary diagnosis of anterior uveitis. Prior treatment with anti-IL-6 or IL-6R antagonist therapies, including tocilizumab and sarilumab.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uveitis

Intervention

Drug:
• Sarilumab SAR153191/REGN88
Pharmaceutical form:Prefilled syringes Route of administration: subcutaneous
• Prednisone
Pharmaceutical form:tablet Route of administration: oral
• Methotrexate
Pharmaceutical form:solution Route of administration: intravenous
• Folic/folinic acid
Pharmaceutical form:tablet Route of administration: oral

Other:
• Sarilumab (SAR153191/REGN88) placebo
Pharmaceutical form:Prefilled syringes Route of administration: subcutaneous

Locations

Country	Name	City	State
Czech Republic	Investigational Site Number 203001	Brno
Czech Republic	Investigational Site Number 203002	Praha 2
France	Investigational Site Number 250001	Paris
France	Investigational Site Number 250002	Paris
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380003	Padova
Italy	Investigational Site Number 380004	Reggio Emilia
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724003	Barcelona
Turkey	Investigational Site Number 792001	Ankara
Turkey	Investigational Site Number 792005	Ankara
Turkey	Investigational Site Number 792002	Istanbul
Turkey	Investigational Site Number 792003	Istanbul
Turkey	Investigational Site Number 792004	Izmir
Turkey	Investigational Site Number 792006	Izmir
United States	Investigational Site Number 840006	Arlington	Texas
United States	Investigational Site Number 840007	Cleveland	Ohio
United States	Investigational Site Number 840009	Omaha	Nebraska
United States	Investigational Site Number 840005	Slingerlands	New York
United States	Investigational Site Number 840008	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Czech Republic,  France,  Italy,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with at least 2-step reduction in Vitreous Haze OR dose of prednisone < 10 mg/day		At 16 weeks	No
Secondary	Mean change from baseline in VH		At 16 weeks	No
Secondary	Percentage of patients with anterior chamber score = 0 or at least 2-step reduction in score (Tyndall and flare according to the SUN classification)		At 16 weeks	No
Secondary	Mean change from baseline in BCVA (ETDRS letters score)		Up to 16 weeks	No
Secondary	Mean change from baseline in central retinal thickness measured with Optical Coherence Tomography (OCT)		At 16 weeks	No
Secondary	Percentage of patients with Central Retinal Thickness <300 microns		At 16 weeks	No
Secondary	Percentage of patients without retinal vessel leakage on fluorescein angiography compared to baseline		At 16 weeks	No
Secondary	Percentage of patients with dose of prednisone = 5mg/day (or equivalent oral corticosteroid)		At 16 weeks	No
Secondary	Pharmacokinetics assessment		At 16 weeks	No
Secondary	Adverse events including Serious Adverse Events and Adverse Events of Special Interest		At 16 weeks	Yes
Secondary	Assessment of clinical laboratory data		At 16 weeks	Yes