Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis

NCT ID: NCT01900431

Last Updated: 2017-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-04-30

Brief Summary

Primary Objective:

To evaluate the efficacy of sarilumab at Week 16 in participants 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 participants 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 participants. To evaluate the immunogenicity with anti-drug antibodies (ADA).

Detailed Description

The total duration per participant was up to 58 weeks, which included a 2 week screening period, 16 weeks principal treatment period (Part A), 34 weeks extension treatment period (Part B) or open label treatment period (Part C), and 6 weeks after last treatment administration.

Participants with decrease in vitreous haze (VH) ≥2; or corticosteroids dose <10 mg/day at Week 16 were considered as responders. Participants who did not complete the principal treatment period (Part A) due to lack of efficacy; or no decrease in VH ≥2 and corticosteroids dose ≥10 mg/day at Week 16; or no decrease in VH ≥2 and corticosteroids dose missing at Week 16; or non-responder according to medical review, were considered as non-responders.

Responder participants, observed at Week 16 (at the end of Part A), were invited to continue in the extension treatment period (Part B).

Non-responder participants, observed within the first 16 weeks, were offered to be treated by open-label sarilumab (Part C).

Conditions

Uveitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Placebo (for Sarilumab) subcutaneous (SC) injection every 2 weeks (q2w) for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and \<80 mg/day as single therapy or in combination with Methotrexate (MTX) 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).

Group Type: PLACEBO_COMPARATOR

Sarilumab

Intervention Type: DRUG

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Methotrexate

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular

Folic/folinic acid

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Placebo (for Sarilumab)

Intervention Type: OTHER

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Sarilumab 200 mg q2w

Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and \<80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C).

Group Type: EXPERIMENTAL

Sarilumab

Intervention Type: DRUG

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Methotrexate

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular

Folic/folinic acid

Intervention Type: DRUG

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Interventions

Sarilumab

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Intervention Type: DRUG

Prednisone

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Intervention Type: DRUG

Methotrexate

Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular

Intervention Type: DRUG

Folic/folinic acid

Pharmaceutical form: Tablet or Capsule; Route of administration: Oral

Intervention Type: DRUG

Placebo (for Sarilumab)

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Intervention Type: OTHER

Other Intervention Names

SAR153191/REGN88

Eligibility Criteria

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 participants with "active disease" as defined above were 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, participants must be receiving oral prednisone (≥15 mg and <80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with MTX (≤25 mg/week) orally or intravenously or intramuscular or subcutaneous). -
• Participants could be receiving one or several of the following therapies: Azathioprine (≤2.5 mg/kg/day), Mycophenolate mofetil (≤2 g daily, orally), Cyclosporine (≤4 mg/kg daily, orally), Tacrolimus (≤4 mg daily, orally).
• The doses might not had been increased for at least 4 weeks prior to the randomization visit.
• At randomization, participants had been receiving oral prednisone (≥15 mg and <80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with MTX (≤25 mg/week) orally or intravenously or intramuscular or subcutaneous).
• Azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus had to be permanently discontinued at least 48 hours prior to the first study treatment injection, or longer as per Investigator's judgment. These immunomodulatory therapies (IMTs) were not permitted anytime during the treatment period.
• Signed written informed consent.

Exclusion Criteria

• Participants with best-corrected visual acuity (BCVA) worse than 20 early treatment diabetic retinopathy study (ETDRS) letters in at least one eye.
• Participants with confirmed or suspected uveitis of infectious etiology or uveitis of traumatic etiology.
• Participants with primary diagnosis of anterior uveitis.
• Prior treatment with anti-interleukin-6 (IL-6) or interleukin-6 receptor complex (IL-6R) antagonist therapies, including tocilizumab and sarilumab.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840008

Worcester, Massachusetts, United States

Investigational Site Number 840009

Omaha, Nebraska, United States

Investigational Site Number 840005

Slingerlands, New York, United States

Investigational Site Number 840007

Cleveland, Ohio, United States

Investigational Site Number 840006

Arlington, Texas, United States

Investigational Site Number 203001

Brno, , Czechia

Investigational Site Number 203002

Prague, , Czechia

Investigational Site Number 250001

Paris, , France

Investigational Site Number 250002

Paris, , France

Investigational Site Number 380001

Milan, , Italy

Investigational Site Number 380003

Padua, , Italy

Investigational Site Number 380004

Reggio Emilia, , Italy

Investigational Site Number 724003

Barcelona, , Spain

Investigational Site Number 724001

Barcelona, , Spain

Investigational Site Number 792001

Ankara, , Turkey (Türkiye)

Investigational Site Number 792005

Ankara, , Turkey (Türkiye)

Investigational Site Number 792002

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792003

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792004

Izmir, , Turkey (Türkiye)

Investigational Site Number 792006

Izmir, , Turkey (Türkiye)

Countries

United States; Czechia; France; Italy; Spain; Turkey (Türkiye)

Other Identifiers

2012-004845-34

Identifier Type: -

Identifier Source: secondary_id

U1111-1130-6500

Identifier Type: OTHER

Identifier Source: secondary_id

ACT13480

Identifier Type: -

Identifier Source: org_study_id