search
Back to results

Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis (SARILNIUSATURN)

Primary Purpose

Uveitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sarilumab
Prednisone
Methotrexate
Folic/folinic acid
Placebo (for Sarilumab)
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840008
  • Investigational Site Number 840009
  • Investigational Site Number 840005
  • Investigational Site Number 840007
  • Investigational Site Number 840006
  • Investigational Site Number 203001
  • Investigational Site Number 203002
  • Investigational Site Number 250001
  • Investigational Site Number 250002
  • Investigational Site Number 380001
  • Investigational Site Number 380003
  • Investigational Site Number 380004
  • Investigational Site Number 724003
  • Investigational Site Number 724001
  • Investigational Site Number 792001
  • Investigational Site Number 792005
  • Investigational Site Number 792002
  • Investigational Site Number 792003
  • Investigational Site Number 792004
  • Investigational Site Number 792006

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sarilumab 200 mg q2w

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline in VH Scale at Week 16
Change from baseline in VH scale 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) were equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Least squares (LS) mean was calculated using mixed model for repeated measurements (MMRM) model with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects as well as fixed continuous covariate of baseline adjudicated VH.
Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16
Participants with AC cell score = 0 or with ≥2 step reduction from baseline at Week 16 were evaluated. Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: grade 0 = no cells; grade +0.5 = 1 - 5 cells; grade +1 = 6 - 25 cells; grade +2= 26 - 50 cells; grade +3 = too many to count.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16
BCVA score is based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters, and then at 1 meter. The range of ETDRS is 0 to 100 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline BCVA.
Change From Baseline in Central Retinal Thickness (CRT) At Week 16
CRT was measured by spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Percent Change From Baseline in CRT at Week 16
CRT was measured by SD-OCT, a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Percentage of Participants With CRT Thickness <300 Microns at Week 16
Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16
Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16
Participants with prednisone dose ≤5 mg/day (or equivalent oral corticosteroid) at Week 16 were evaluated.
Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration
Serum functional (unbound) sarilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method with a lower limit of quantification (LLOQ) of 294 ng/mL. Concentrations below LLOQ were set to zero for samples at predose. Post-treatment concentrations below LLOQ were replaced by LLOQ/2. The samples were considered non-eligible for the analysis if the previous dosing time was <11 days or >17 days before the sampling time for every other week regimens.

Full Information

First Posted
July 11, 2013
Last Updated
May 23, 2017
Sponsor
Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT01900431
Brief Title
Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Sarilumab 200 mg q2w
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Sarilumab
Other Intervention Name(s)
SAR153191/REGN88
Intervention Description
Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular
Intervention Type
Drug
Intervention Name(s)
Folic/folinic acid
Intervention Description
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
Intervention Type
Other
Intervention Name(s)
Placebo (for Sarilumab)
Intervention Description
Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous
Primary Outcome Measure Information:
Title
Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16
Description
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.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline in VH Scale at Week 16
Description
Change from baseline in VH scale 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) were equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Least squares (LS) mean was calculated using mixed model for repeated measurements (MMRM) model with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects as well as fixed continuous covariate of baseline adjudicated VH.
Time Frame
Baseline to Week 16
Title
Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16
Description
Participants with AC cell score = 0 or with ≥2 step reduction from baseline at Week 16 were evaluated. Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: grade 0 = no cells; grade +0.5 = 1 - 5 cells; grade +1 = 6 - 25 cells; grade +2= 26 - 50 cells; grade +3 = too many to count.
Time Frame
Week 16
Title
Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16
Description
BCVA score is based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters, and then at 1 meter. The range of ETDRS is 0 to 100 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline BCVA.
Time Frame
Baseline to Week 16
Title
Change From Baseline in Central Retinal Thickness (CRT) At Week 16
Description
CRT was measured by spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Time Frame
Baseline to Week 16
Title
Percent Change From Baseline in CRT at Week 16
Description
CRT was measured by SD-OCT, a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Time Frame
Baseline to Week 16
Title
Percentage of Participants With CRT Thickness <300 Microns at Week 16
Time Frame
Week 16
Title
Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16
Time Frame
Week 16
Title
Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16
Description
Participants with prednisone dose ≤5 mg/day (or equivalent oral corticosteroid) at Week 16 were evaluated.
Time Frame
Week 16
Title
Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration
Description
Serum functional (unbound) sarilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method with a lower limit of quantification (LLOQ) of 294 ng/mL. Concentrations below LLOQ were set to zero for samples at predose. Post-treatment concentrations below LLOQ were replaced by LLOQ/2. The samples were considered non-eligible for the analysis if the previous dosing time was <11 days or >17 days before the sampling time for every other week regimens.
Time Frame
Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840008
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01608
Country
United States
Facility Name
Investigational Site Number 840009
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5540
Country
United States
Facility Name
Investigational Site Number 840005
City
Slingerlands
State/Province
New York
ZIP/Postal Code
12159
Country
United States
Facility Name
Investigational Site Number 840007
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Investigational Site Number 840006
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Investigational Site Number 203001
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Investigational Site Number 203002
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Investigational Site Number 250001
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Investigational Site Number 250002
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Investigational Site Number 380001
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Investigational Site Number 380003
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Investigational Site Number 380004
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
Investigational Site Number 724003
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
Investigational Site Number 724001
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Investigational Site Number 792001
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Investigational Site Number 792005
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Investigational Site Number 792002
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Investigational Site Number 792003
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Investigational Site Number 792004
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Investigational Site Number 792006
City
Izmir
ZIP/Postal Code
35100
Country
Turkey

12. IPD Sharing Statement

Learn more about this trial

Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis

We'll reach out to this number within 24 hrs