- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01900431
Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis (SARILNIUSATURN)
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)
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).
Study Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Brno, Czechia, 62500
- Investigational Site Number 203001
-
Praha 2, Czechia, 12808
- Investigational Site Number 203002
-
-
-
-
-
Paris, France, 75013
- Investigational Site Number 250001
-
Paris, France, 75571
- Investigational Site Number 250002
-
-
-
-
-
Milano, Italy, 20132
- Investigational Site Number 380001
-
Padova, Italy, 35128
- Investigational Site Number 380003
-
Reggio Emilia, Italy, 42100
- Investigational Site Number 380004
-
-
-
-
-
Barcelona, Spain, 08907
- Investigational Site Number 724001
-
Barcelona, Spain, 08028
- Investigational Site Number 724003
-
-
-
-
-
Ankara, Turkey, 06100
- Investigational Site Number 792001
-
Ankara, Turkey, 06100
- Investigational Site Number 792005
-
Istanbul, Turkey, 34093
- Investigational Site Number 792002
-
Istanbul, Turkey, 34098
- Investigational Site Number 792003
-
Izmir, Turkey, 35100
- Investigational Site Number 792004
-
Izmir, Turkey, 35100
- Investigational Site Number 792006
-
-
-
-
Massachusetts
-
Worcester, Massachusetts, United States, 01608
- Investigational Site Number 840008
-
-
Nebraska
-
Omaha, Nebraska, United States, 68198-5540
- Investigational Site Number 840009
-
-
New York
-
Slingerlands, New York, United States, 12159
- Investigational Site Number 840005
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Investigational Site Number 840007
-
-
Texas
-
Arlington, Texas, United States, 76012
- Investigational Site Number 840006
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 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).
|
Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous
Other Names:
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous
|
Experimental: 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).
|
Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous
Other Names:
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
Pharmaceutical form: Tablet or Capsule or Suspension; Route of administration: Orally or intravenously or intramuscular
Pharmaceutical form: Tablet or Capsule; Route of administration: Oral
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16
Time Frame: 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in VH Scale at Week 16
Time Frame: Baseline to 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.
|
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
Time Frame: 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.
|
Week 16
|
Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16
Time Frame: Baseline to 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.
|
Baseline to Week 16
|
Change From Baseline in Central Retinal Thickness (CRT) At Week 16
Time Frame: Baseline to 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.
|
Baseline to Week 16
|
Percent Change From Baseline in CRT at Week 16
Time Frame: Baseline to 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.
|
Baseline to Week 16
|
Percentage of Participants With CRT Thickness <300 Microns at Week 16
Time Frame: Week 16
|
Week 16
|
|
Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16
Time Frame: Week 16
|
Week 16
|
|
Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16
Time Frame: Week 16
|
Participants with prednisone dose ≤5 mg/day (or equivalent oral corticosteroid) at Week 16 were evaluated.
|
Week 16
|
Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration
Time Frame: Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)
|
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.
|
Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Eye Diseases
- Uveal Diseases
- Uveitis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protective Agents
- Dermatologic Agents
- Micronutrients
- Vitamins
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Hematinics
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Leucovorin
- Levoleucovorin
- Prednisone
- Methotrexate
- Folic Acid
Other Study ID Numbers
- ACT13480
- 2012-004845-34
- U1111-1130-6500 (Other Identifier: UTN)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uveitis
-
Priovant Therapeutics, Inc.Active, not recruitingNon-infectious Intermediate Uveitis | Non-infectious Posterior Uveitis | Non-infectious Pan UveitisUnited States
-
University of NebraskaUnknownPosterior Uveitis | Intermediate Uveitis | Pan-uveitisUnited States
-
Stanford UniversitySanten Inc.WithdrawnPanuveitis | Uveitis | Posterior Uveitis | Intermediate UveitisUnited States
-
CHU de Quebec-Universite LavalCompletedIntermediate Uveitis | Anterior UveitisCanada
-
EyePoint Pharmaceuticals, Inc.CompletedPanuveitis | Posterior Uveitis | Intermediate UveitisIndia
-
Johns Hopkins UniversityMacuSight, Inc.CompletedPanuveitis | Uveitis | Posterior Uveitis | Intermediate UveitisUnited States
-
Novartis PharmaceuticalsCompletedNon-infectious Intermediate Uveitis | Non-infectious Posterior Uveitis | Non-infectious PanuveitisUnited States, United Kingdom
-
The New York Eye & Ear InfirmaryUnknownPanuveitis | Uveitis | Posterior Uveitis | Anterior UveitisUnited States
-
Duke UniversityCompletedPosterior Uveitis | Intermediate UveitisUnited States
-
AllerganCompletedPosterior Uveitis | Intermediate UveitisFrance, United Kingdom, United States, Spain, Poland, India, South Africa, Korea, Republic of, Canada, Czech Republic, Australia, Germany, Israel, Switzerland, Portugal, Austria, Brazil, Greece
Clinical Trials on Sarilumab
-
Assistance Publique - Hôpitaux de ParisUnknown
-
Westyn Branch-EllimanCompleted
-
Clinica Universidad de Navarra, Universidad de...Sanofi; Hospital Universitario Infanta LeonorUnknownCOVID-19 Drug TreatmentSpain
-
SanofiRegeneron PharmaceuticalsActive, not recruitingRheumatoid Arthritis -Exposure During PregnancyUnited States, Canada
-
GlaxoSmithKlineIqvia Pty LtdCompletedArthritis, RheumatoidUnited States, Germany, Canada, Czechia, Poland, South Africa, Korea, Republic of, Spain, Japan, Argentina, Belgium, Hungary, United Kingdom, Italy, Lithuania
-
ASST Fatebenefratelli SaccoRecruiting
-
National Institute of Allergy and Infectious Diseases...CompletedIndolent Systemic MastocytosisUnited States
-
Regeneron PharmaceuticalsSanofiCompletedCOVID-19United States
-
Massachusetts General HospitalRegeneron PharmaceuticalsWithdrawn
-
Stanford UniversityCompleted