E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046851 |
E.1.2 | Term | Uveitis |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of sarilumab at week 16 in patients with non-infectious uveitis (NIU). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the change in best corrected visual acuity (BCVA).
To evaluate the safety of subcutaneous sarilumab in patients 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 at W16.
To evaluate the change in ocular inflammation in the anterior chamber.
To evaluate the pharmacokinetics of sarilumab in NIU patients.
To evaluate the immunogenicity with anti-drug antibodies (ADA)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 patients with “active disease” as defined above will be 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, patients must be receiving oral prednisone (≥15 mg and < 80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with Methotrexate (MTX) (≤ 25 mg/week) orally or intravenously or intra muscular or subcutaneous). Patients can be receiving one or several of the following therapies: Azathioprine (≤2.5 mg/kg/day), Mycophenolate mofetil (≤2g daily, orally), Cyclosporine (≤4 mg/kg daily, orally), Tacrolimus (≤4 mg daily, orally).
The doses may not have been increased for at least 4 weeks prior to the randomization visit.
At randomization, patients have been receiving oral prednisone (≥15 mg and < 80 mg/day [or equivalent oral corticosteroid]) as single immunosuppressive therapy or in combination with methotrexate (MTX) (≤ 25 mg/week) orally or intravenously or intra muscular or subcutaneous).
Azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus have to be permanently discontinued at least 48 hours prior to the first study treatment injection, or longer as per Investigator’s judgment. These IMTs are not permitted anytime during the treatment period.
Signed written informed consent. |
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E.4 | Principal exclusion criteria |
Patient with best-corrected visual acuity worse than 20 ETDRS letters in at least one eye.
Patient with confirmed or suspected uveitis of infectious etiology or uveitis of traumatic etiology.
Patient with primary diagnosis of anterior uveitis.
Prior treatment with anti-IL-6 or IL-6R antagonist therapies, including tocilizumab and sarilumab.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with at least 2-step reduction in Vitreous Haze OR dose of prednisone < 10 mg/day |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Mean change from baseline in VH
2) Percentage of patients with anterior chamber score = 0 or at least 2-step reduction in score (Tyndall and flare according to the SUN classification)
3) Mean change from baseline in BCVA (ETDRS letters score)
4) Mean change from baseline in central retinal thickness measured with Optical Coherence Tomography (OCT)
5) Percentage of patients with Central Retinal Thickness <300 microns
6) Percentage of patients without retinal vessel leakage on fluorescein angiography
7) Percentage of patients with dose of prednisone ≤ 5mg/day (or equivalent oral corticosteroid)
8) Pharmacokinetics assessment
9) Adverse events including Serious Adverse Events and Adverse Events of Special Interest
10) Assessment of clinical laboratory data |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
France |
Germany |
Italy |
Spain |
Switzerland |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 28 |