Clinical trial NCT01900431: Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uveitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-07-16
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Change From Baseline in VH Scale at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16
timeFrame: Week 16
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Central Retinal Thickness (CRT) At Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in CRT at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With CRT Thickness <300 Microns at Week 16
timeFrame: Week 16
measure: Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16
timeFrame: Week 16
measure: Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration
timeFrame: Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)
Other outcomes:
Locations:
city: Worcester
country: United States
facility: Investigational Site Number 840008
state: Massachusetts
city: Omaha
country: United States
facility: Investigational Site Number 840009
state: Nebraska
city: Slingerlands
country: United States
facility: Investigational Site Number 840005
state: New York
city: Cleveland
country: United States
facility: Investigational Site Number 840007
state: Ohio
city: Arlington
country: United States
facility: Investigational Site Number 840006
state: Texas
city: Brno
country: Czechia
facility: Investigational Site Number 203001
city: Praha 2
country: Czechia
facility: Investigational Site Number 203002
city: Paris
country: France
facility: Investigational Site Number 250001
city: Paris
country: France
facility: Investigational Site Number 250002
city: Milano
country: Italy
facility: Investigational Site Number 380001
city: Padova
country: Italy
facility: Investigational Site Number 380003
city: Reggio Emilia
country: Italy
facility: Investigational Site Number 380004
city: Barcelona
country: Spain
facility: Investigational Site Number 724003
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Ankara
country: Turkey
facility: Investigational Site Number 792001
city: Ankara
country: Turkey
facility: Investigational Site Number 792005
city: Istanbul
country: Turkey
facility: Investigational Site Number 792002
city: Istanbul
country: Turkey
facility: Investigational Site Number 792003
city: Izmir
country: Turkey
facility: Investigational Site Number 792004
city: Izmir
country: Turkey
facility: Investigational Site Number 792006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: