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UveitisPhase 2SARILNIUSATURNNCT01900431

Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis

A Phase 2 study testing Sarilumab, Prednisone and Methotrexate in people with Uveitis, run by Sanofi at 20 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveitis
What is being tested?
Sarilumab, Prednisone and Methotrexate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
20 sitesin 6 countries
Study dates
Oct 2013to Apr 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥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).
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

20 sites in 6 countries.

20 sites in 6 countries

Turkey (Türkiye)6 sites
  • Investigational Site Number 792001

    Ankara, 06100

  • Investigational Site Number 792005

    Ankara, 06100

  • Investigational Site Number 792002

    Istanbul, 34093

  • Investigational Site Number 792003

    Istanbul, 34098

  • Investigational Site Number 792004

    Izmir, 35100

  • Investigational Site Number 792006

    Izmir, 35100

Other trials in Turkey (Türkiye)

United States5 sites
  • Investigational Site Number 840006

    Arlington, Texas, 76012

  • Investigational Site Number 840007

    Cleveland, Ohio, 44195

  • Investigational Site Number 840009

    Omaha, Nebraska, 68198-5540

  • Investigational Site Number 840005

    Slingerlands, New York, 12159

  • Investigational Site Number 840008

    Worcester, Massachusetts, 01608

Other trials in United States

Italy3 sites
  • Investigational Site Number 380001

    Milan, 20132

  • Investigational Site Number 380003

    Padova, 35128

  • Investigational Site Number 380004

    Reggio Emilia, 42100

Other trials in Italy

Czechia2 sites
  • Investigational Site Number 203001

    Brno, 62500

  • Investigational Site Number 203002

    Prague, 12808

Other trials in Czechia

France2 sites
  • Investigational Site Number 250001

    Paris, 75013

  • Investigational Site Number 250002

    Paris, 75571

Other trials in France

Spain2 sites
  • Investigational Site Number 724003

    Barcelona, 08028

  • Investigational Site Number 724001

    Barcelona, 08907

Other trials in Spain

About this study

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)

Primary Objective:

To evaluate the efficacy of sarilumab at Week 16 in participants with non-infectious uveitis (NIU).

Read more

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).

Read the 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
Being tested
Sarilumab, Prednisone, Methotrexate, Folic/folinic acid, Placebo (for Sarilumab)
Medical subject headings
Uveitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SarilumabDrug

    Also called SAR153191/REGN88

    Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

  • PrednisoneDrug

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

  • MethotrexateDrug

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

  • Folic/folinic acidDrug

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

  • Placebo (for Sarilumab)Other

    Pharmaceutical form: Prefilled syringes; Route of administration: Subcutaneous

Study groups in NCT01900431
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo (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).
Receives: Drug: Sarilumab; Drug: Prednisone; Drug: Methotrexate; Drug: Folic/folinic acid; Other: Placebo (for Sarilumab)
Sarilumab 200 mg q2wExperimentalSarilumab 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).
Receives: Drug: Sarilumab; Drug: Prednisone; Drug: Methotrexate; Drug: Folic/folinic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 16

Secondary outcomes (9)
  1. 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.

    Measured: Baseline to Week 16

  2. 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.

    Measured: Week 16

  3. 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.

    Measured: Baseline to Week 16

  4. 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.

    Measured: Baseline to Week 16

  5. 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.

    Measured: Baseline to Week 16

  6. Percentage of Participants With CRT Thickness <300 Microns at Week 16

    Measured: Week 16

  7. Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16

    Measured: Week 16

  8. 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.

    Measured: Week 16

  9. 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.

    Measured: Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionJul 2015
  4. Study completionApr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01900431
Sponsor's protocol ID
ACT13480
Other IDs
2012-004845-34, U1111-1130-6500
Acronym
SARILNIUSATURN
Status last verified
May 2017
First submitted
11 Jul 2013
Last updated
20 Jun 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sarilumab, Prednisone and Methotrexate in people with Uveitis, run by Sanofi at 20 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Turkey (Türkiye), United States, Italy, Czechia, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.

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