Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis

NCT01900431 | Completed Phase 2 Results DMC

• 3 other identifiers: ACT134802012-004845-34U1111-1130-6500
• Study Type: interventional
• Target: 58
• Locations: 6 countries
• Sites: 20

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).

Conditions

Uveitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16

  At least 2-step reduction in VH per central review from baseline was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 \[low opacity\] to 8 \[more opacity\]) images (in increasing order of opacity) are equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Participants with prednisone dose \<10 mg/day (or equivalent oral corticosteroid) were also evaluated.

  Week 16

Secondary Outcomes (9)

• Change From Baseline in VH Scale at Week 16

  Baseline to Week 16

• Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16

  Week 16

• Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16

  Baseline to Week 16

• Change From Baseline in Central Retinal Thickness (CRT) At Week 16

  Baseline to Week 16

• Percent Change From Baseline in CRT at Week 16

  Baseline to Week 16

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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).

Drug: Sarilumab; Drug: Prednisone; Drug: Methotrexate; Drug: Folic/folinic acid; Other: Placebo (for Sarilumab)

Sarilumab 200 mg q2w

EXPERIMENTAL

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).

Drug: Sarilumab; Drug: Prednisone; Drug: Methotrexate; Drug: Folic/folinic acid

Interventions

Sarilumab DRUG

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Also known as: SAR153191/REGN88

Placebo; Sarilumab 200 mg q2w

Prednisone DRUG

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

Placebo; Sarilumab 200 mg q2w

Methotrexate DRUG

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

Placebo; Sarilumab 200 mg q2w

Folic/folinic acid DRUG

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

Placebo; Sarilumab 200 mg q2w

Placebo (for Sarilumab) OTHER

Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Placebo

Eligibility Criteria

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

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (20)

Investigational Site Number 840008

Worcester, Massachusetts, 01608, United States

Location

Investigational Site Number 840009

Omaha, Nebraska, 68198-5540, United States

Location

Investigational Site Number 840005

Slingerlands, New York, 12159, United States

Location

Investigational Site Number 840007

Cleveland, Ohio, 44195, United States

Location

Investigational Site Number 840006

Arlington, Texas, 76012, United States

Location

Investigational Site Number 203001

Brno, 62500, Czechia

Location

Investigational Site Number 203002

Prague, 12808, Czechia

Location

Investigational Site Number 250001

Paris, 75013, France

Location

Investigational Site Number 250002

Paris, 75571, France

Location

Investigational Site Number 380001

Milan, 20132, Italy

Location

Investigational Site Number 380003

Padua, 35128, Italy

Location

Investigational Site Number 380004

Reggio Emilia, 42100, Italy

Location

Investigational Site Number 724003

Barcelona, 08028, Spain

Location

Investigational Site Number 724001

Barcelona, 08907, Spain

Location

Investigational Site Number 792001

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 792005

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 792002

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number 792003

Istanbul, 34098, Turkey (Türkiye)

Location

Investigational Site Number 792004

Izmir, 35100, Turkey (Türkiye)

Location

Investigational Site Number 792006

Izmir, 35100, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Uveitis

Interventions

sarilumab; Prednisone; Methotrexate; Leucovorin

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 16, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: April 1, 2016
• Last Updated: June 20, 2017
• Results First Posted: June 20, 2017

Record last verified: 2017-05

Locations

US (5); CZ (2); IT (3); ES (2); FR (2); TU (6)