E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Non-infectious Intermediate-, Posterior-, or Pan-uveitis |
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E.1.1.1 | Medical condition in easily understood language |
Uveitis refers to inflammation in the uveal tract of the eye which includes the iris, ciliary body, and choroid. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022557 |
E.1.2 | Term | Intermediate uveitis |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033687 |
E.1.2 | Term | Panuveitis |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036370 |
E.1.2 | Term | Posterior uveitis |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The objective of this study is to evaluate the efficacy and safety of adalimumab 80 mg loading dose followed by 40 mg dose given every other week (eow) subcutaneously (SC) starting at Week 1 compared with placebo as maintenance therapy in subjects requiring high dose corticosteroids for active non-infectious intermediate-, posterior-, or pan-uveitis. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject is ≥ 18 years of age.
Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis.
Subject must have active disease at the Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of maintenance therapy with oral prednisone at a dose of ≥ 10 mg/day to ≤ 60 mg/day (or oral corticosteroid equivalent):
● Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
● ≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria)
● ≥ 2+ vitreous haze (National Eye Institute [NEI]/SUN criteria)
Subject is on oral prednisone at a dose of ≥ 10 mg/day to ≤ 60 mg/day (or oral corticosteroid equivalent) for at least 2 weeks prior to Screening and remains on the same dose from Screening to Baseline visit.
Subjects who do not have previous, active or latent TB. |
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E.4 | Principal exclusion criteria |
1. Subject with isolated anterior uveitis.
2. Subject with prior inadequate response to high-dose oral
corticosteroids.
3. Subject with confirmed or suspected infectious uveitis, including but not limited to
infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease,
toxoplasmosis, Human T-Lymphotropic Virus Type 1 (HTLV-1) infection,
Whipple's disease, herpes zoster virus (HZV) and herpes simplex virus (HSV).
4. Subject with presumed ocular histoplasmosis syndrome (POHS).
5. Subject with ocular masquerade syndromes, such as ocular lymphoma.
6. Subject with serpiginous choroidopathy.
7. Subject has a contraindication to pupil dilation with mydriatic eyedrops.
8. Subject with corneal or lens opacity that precludes visualization of the fundus or
that likely requires cataract surgery during the duration of the trial.
9. Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications
or evidence of glaucomatous optic nerve injury.
10. Subject with Best Corrected Visual Acuity (BCVA) less than 20 letters (ETDRS [Early Treatment Diabetic Retinopathy Study]) in at least one eye at the Baseline visit.
11. Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) and symptoms and/or Magnetic Resonance Imaging (MRI) findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis or panuveitis that have signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) must have a brain MRI within 90 days prior to the Baseline visit.
12. Subject has previous exposure to anti-TNF therapy or any biologic therapy (except
intravitreal anti-vascular endothelial growth factor [VEGF] therapy [See Exclusion
Criterion No. 43]) with a potential therapeutic impact on non infectious uveitis.
13. Subject on more than 1 immunosuppressive therapy (not including corticosteroids)
at Baseline.
14. Subject on concomitant immunosuppressive therapy other than methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine, or tacrolimus at Baseline.
15. If entering the study on 1 concomitant immunosuppressive therapy, dose has been
increased within the last 28 days prior to Baseline visit or is not within the
following allowable doses at the Baseline visit:
● Methotrexate (MTX) ≤ 25 mg per week
● Cyclosporine ≤ 4 mg/kg per day
● Mycophenolate mofetil ≤ 2 grams per day or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid) at an equivalent dose approved by the Medical Monitor.
● Azathioprine ≤ 175 mg per day
●Tacrolimus (oral formulation) ≤ 8 mg per day
16. Subject with prior or current use of chlorambucil.
17. Subject has received Retisert® (glucocorticosteroid implant) within 3 years prior to
the Baseline visit or has had complications related to the device.
Subject has had Retisert® (glucocorticosteroid implant) removed within 90 days
prior to the Baseline visit or has had complications related to the removal of the
device.
18. Subject has received intraocular or periocular corticosteroids within 30 days prior
to the Baseline visit.
19. Subject with history of prior ocular surgery within 90 days prior to the Baseline visit with the exception of refractive laser surgery or retinal laser photocoagulation or YAG (neodymium-doped yttrium aluminium garnet) posterior capsulotomy. These three exceptions are exclusionary within 30 days prior to Baseline.
20. Subject with any planned (elective) eye surgery within the next 80 weeks from
Baseline.
21. Subject with proliferative or severe non-proliferative diabetic retinopathy or
clinically significant macular edema due to diabetic retinopathy.
22. Subject with neovascular/wet age-related macular degeneration.
23. Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction,
epiretinal membranes, etc.) with the potential for macular structural damage
independent of the inflammatory process.
40. Subject with severe vitreous haze that precludes visualization of the fundus at the
Baseline visit.
41. Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to
Baseline visit.
42. Subject has received intravitreal MTX within 90 days prior to the Baseline visit.
43. Subject has received intravitreal anti-VEGF therapy:
- within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab);
- or within 60 days of the Baseline visit for anti-VEGF Trap (Aflibercept).
51. Subject with intolerance to high-dose oral corticosteroids (equivalent of oral prednisone 1 mg/kg/day or 60 to 80 mg/day).
52. Subject on cyclophosphamide within 30 days prior to the Baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to treatment failure. Please refer to section 5.3.3.1 of the study protocol for further information. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It will be evaluated at Week 6 and each visit thereafter. |
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E.5.2 | Secondary end point(s) |
1. Change in Anterior Chamber (AC) cell grade in each eye from Week 6 to the Final/Early Termination visit.
2. Change in Vitreous Haze grade (NEI/SUN criteria) in each eye from Week 6 to the Final/Early Termination visit.
3. Change in logMAR BCVA in each eye from Week 6 to the Final/Early Termination Visit
4. Time to OCT evidence of macular edema in at least one eye on or after Week 6
5. Percentage change in central retinal thickness in each eye from Baseline to the Final/Early Termination visit
6. Change in NEI Visual Functioning Questionnaire (VFQ-25) composite score from Week 6 to the Final/Early Termination visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please see details in E.5.2. |
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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 | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
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 | 43 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Mexico |
Netherlands |
Poland |
Portugal |
Spain |
Switzerland |
United Kingdom |
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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The end-of-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is later (refer section 13 of the protocol) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |