E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-infectious, Intermediate-, Posterior- or Pan-uveitis |
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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 | 22.1 |
E.1.2 | Level | LLT |
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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036370 |
E.1.2 | Term | Posterior uveitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that izokibep is efficacious compared to placebo, as measured by time to treatment failure occurring at or after week 10 and up to week 52 |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate that izokibep is efficacious, as measured by: • Proportion of subjects that achieve quiescence at week 10 • Change in BCVA from best state achieved before week 10 to week 24 • Change in the NEI VFQ-25 score from best state achieved before week 10 to week 24 • Change in central retinal thickness (by SD-OCT) from baseline to week 10 • Change in central retinal thickness (by SD-OCT) from best state achieved ≤ week 10 up to week 52 -To assess the safety and tolerability of izokibep as measured by the incidence of TEAEs, events of special interest, SAEs and clinically significant lab values and vital signs - To assess the immunogenicity of izokibep as measured by the presence of treatment-emergent ADAs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject(male and female) must be ≥ 18 and ≤ 75 years of age - Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis - Active disease defined by the presence of at least 1 of the following criteria in at least 1 eye despite treatment with stable doses of corticosteroids for at least 2 weeks prior to day 1: o Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography (FA), and Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine whether a lesion is active or inactive (the central reading center assessment using FA, fundus photography and/or SD-OCT is required to confirm eligibility prior to day 1). o ≥ 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus photography (the central reading center assessment using fundus photography is required to confirm eligibility prior to day 1). - Currently receiving treatment with oral corticosteroids (≥ 7.5 mg/day to ≤ 40 mg/day oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at least 2 weeks prior to day 1. - No known history of active tuberculosis (TB). - Subject has a negative TB test at screening, - Male and Female participants of childbearing potential must use effective methods of contraception
For a complete overview of the inclusion criteria refer to the protocol. |
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E.4 | Principal exclusion criteria |
- Subject with isolated anterior uveitis - Subject with serpiginous choroidopathy - Subject with confirmed or suspected infectious uveitis - Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the study - Planned (elective) eye surgery during the course of the study - History of prior refractive laser surgery, laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation), retinal laser photocoagulation, or neodymium-doped yttrium aluminum garnet posterior capsulotomy ≤ 30 days before day 1 - History of any other prior ocular surgery ≤ 3 months prior to day 1 except surgery for cosmetic reasons that is not expected to impact vision - Subject with intraocular pressure of ≥ 25 mmHg while on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury - Subject with severe vitreous haze that precludes visualization of the fundus prior to first dose of study drug - Subject has a contraindication for mydriatic eye drops OR subject cannot be dilated sufficiently well to permit good fundus visualization - Subject with BCVA < 20 letters (Early Treatment Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study drug - Subject with proliferative or severe non-proliferative retinopathy or clinically significant macular edema due to diabetic retinopathy - Subject with neovascular/wet age-related macular degeneration - Subject with an abnormality of the vitreo-retinal interface (eg, vitreomacular traction, epiretinal membranes) with the potential for macular structural damage independent of the inflammatory process - Subject with a history of active scleritis ≤ 12 months of first dose of study drug - Active IBD within 3 years prior to enrollment - Active infection or history of infection - Candida infection requiring systemic treatment ≤ 3 months prior to first dose of study drug - Uncontrolled, clinically significant system disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), moderate to severe renal disease, moderate to severe liver disease, as determined by investigator - History of demyelinating disease (including myelitis) or neurological symptoms suggestive of demyelinating disease - Malignancy within 5 years - History or evidence of any clinically significant disorder, condition, or disease that, in the opinion of the investigator, may pose a risk to subject safety or interfere with the study evaluation, procedures or completion - Tuberculosis or fungal infection seen on available chest x-ray taken ≤ 3 months of screening or at screening (Exception: documented evidence of completed treatment and clinically resolved) - Known history of human immunodeficiency virus (HIV). - Prior exposure to biologics that had a potential or known association with progressive multifocal leukoencephalopathy (ie, natalizumab [Tysabri®], rituximab [Rituxan®] or efalizumab [Raptiva®]) - Exposure to TNF-α inhibitors, IL-1, IL-12, IL-23, IL-12/23 receptor inhibitors or Janus kinase inhibitors within 5 half-lives prior to first dose of study drug - Positive hepatitis B surface antigen (HBsAg) or detected sensitivity on the hepatitis B virus DNA polymerase chain reaction (PCR) qualitative test for hepatitis B core antibody (HBcAb)/hepatitis B surface antibody (HBsAb) positive subjects OR positive hepatitis C virus antibody test at screening - A positive test for syphilis at screening - Laboratory abnormalities at screening
For a complete overview of the exclusion criteria refer to the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to treatment failure |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At or after week 10 / time to treatment failure |
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E.5.2 | Secondary end point(s) |
- Quiescence - BCVA - NEI VFQ-25 - Central retinal thickness - TEAEs, events of special interest and SAEs - Laboratory values and vital signs - ADAs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Quiescence at week 10 - BCVA from best state achieved before week 10 to week 24 - NEI VFQ-25 score from best state achieved before week 10 to week 24 - Central retinal thickness (by SD-OCT) from baseline to week 10 - Central retinal thickness (by SD-OCT) from best state achieved ≤ week 10 up to week 52 From start to end of study: - Incidence of TEAEs, events of special interest, SAEs - Laboratory values and vital signs at collected timepoints - ADAs |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
United States |
Austria |
Czechia |
France |
Germany |
Italy |
Spain |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 21 |