E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-infectious intermediate, posterior, or pan-uveitis |
|
E.1.1.1 | Medical condition in easily understood language |
non-infectious intermediate, posterior, or pan-uveitis |
|
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 | 20.0 |
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 |
|
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 |
Primary objective: To evaluate the efficacy of ABY-035 in treating active uveitis from Baseline (BL) up to week 10 (W10).
|
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of ABY-035 in preventing relapse/recurrence in inactive uveitis beyond W10 up to W50 • To evaluate the safety of ABY-035 • To characterize the exposure of ABY-035 in plasma • To assess the immunogenicity of ABY-035 as measured by the presence of anti-drug antibodies (ADA) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1] Signed informed consent and signed data protection declaration 2] ≥18 years of age at SCR 3] Previously documented medical history with diagnosed unilateral or bilateral NIIPPU 4] Active disease at BL defined by the presence of at least 1 of the following criteria in at least one eye despite treatment with stable doses of corticosteroids for at least 2 weeks: a) Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by Dilated Indirect Ophthalmoscopy (DIO),Fundus Photography, Fluorescein angiography (FA), Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine whether a lesion is active or inactive (the central reader’s assessment using FA, fundus photography and/or SD-OCT is required to confirm eligibility). b) ≥2+ vitreous haze ( NEI/SUN criteria) by DIO and Fundus Photography (the central reader’s assessment using Fundus Photography is required to confirm eligibility). 5] On treatment with oral corticosteroids (≥7 to ≤40 mg/day oral prednisolone/pre dnisone or equivalent) at a stable dose for at least 2 weeks before BL 6] For females of non-childbearing potential: Post-menopausal or surgically sterile 7] For females of childbearing potential: Negative human chorionic gonadotropin (hCG) test at SCR visit AND practicing adequate contraception (see section 7.1.7) from SCR to FU PK/ADA/preg (section 6.2.6) 8] For males: if having a female partner, the partner should be of non-childbearing potential (see inclusion criteria 6) OR using an adequate method of contraception (see section 7.1.7) from SCR to FU PK/ADA/preg (see 6.2.6) 9] Able and willing to comply with the trial directives (as per the investigator's judgment) |
|
E.4 | Principal exclusion criteria |
1] History of hypersensitivity or allergy to ABY-035 or its excipients 2] History of hypersensitivity or allergy to fluorescein dye 3] Previous enrollment or randomization in the trial 4] Participation in another interventional clinical trial within 30 days before SCR or administration of another IMP within 5 half-lives (for experimental biologics: 6 months or 5 half-lives, whichever is longer) before BL 5] Evidence or suspicion of social drug and/or alcohol abuse or dependence, according to the judgment of the investigator 6] Females who are currently pregnant, who intend to become pregnant during the trial, or who are breastfeeding 7] The subject is an investigator or belongs to the personnel of the trial site, the sponsor or involved service providers and/or their immediate families (partner, spouse, parent, child, or sibling, whether biological or legally adopted) 8] Subject with any medical or psychiatric condition which, in the investigator's opinion, would preclude the subject from adhering to the protocol or completing the clinical trial per protocol 9] The subject is considered to belong to a vulnerable population (e.g. placed under guardianship, imprisoned, other) Criteria that relate to ocular conditions (and the etiology thereof) 10] Subject with isolated anterior uveitis 11] Subject with Occlusive Behçet's disease, Acute Posterior Multifocal Placoid Pigment Epitheliopathy, Acute Posterior Pigment Epithelitis, Multiple Evanescent White Dot Syndrome, Punctate Inner Choroiditis or serpiginous choroidopathy 12] Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, syphilis, cytomegalovirus, Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 infection, Whipple's disease, herpes zoster virus, and herpes simplex virus 13] Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial 14] Planned (elective) eye surgery within 80 weeks after BL 15] History of prior refractive laser surgery, retinal laser photocoagulation, or neodymium-doped yttrium aluminium garnet posterior capsulotomy within 30 days before BL 16] History of any other prior ocular surgery within 90 days before BL 17] Subject with intraocular pressure (IOP) of ≥25 mmHg while on ≥2 glaucoma medications or evidence of glaucomatous optic nerve injury 18] Subject with severe vitreous haze that precludes visualization of the fundus at BL 19] Subject has a contraindication for mydriatic eye drops OR subject cannot be dilatated sufficiently well to permit good fundus visualization 20] Subject with BCVA <20 letters (ETDRS) in at least one eye at BL 21] Subject with intermediate uveitis or panuveitis who has presence or history of whitish exudates on the inferior pars plana (snowbanking) or vitreal inflammatory aggregates (snowballs) in combination with a medical history or signs or symptoms suggestive of a demyelinating disease such as multiple sclerosis 22] Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy 23] Subject with neovascular/wet age-related macular degeneration 24] Subject with an abnormality of the vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process 25] Subject with a history of active scleritis within 12 months of SCR Criteria that relate to comorbidity 26] Uncontrolled inflammatory bowel disease 27] Infection requiring treatment with IV anti-infectives within 30 days before BL or oral anti-infectives within 14 days before BL 28] Subject with any active infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the trial 29] History or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 3 years (except for basal cell or squamous cell carcinoma of the skin that had been fully excised with no evidence of recurrence)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary: The number and proportion of subjects with Complete Response at week 10. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints (Efficacy) supporting the primary objective related to the treatment of active disease (≤W10): •Change in ACC grade from BL to W10 or to discontinuation of IMP, if earlier •Change in vitreous haze grade (NEI/SUN criteria) from BL to W10 or to discontinuation of IMP, if earlier •Change in BCVA using logMAR calculation from BL to W10 or to discontinuation of IMP, if earlier •Change in central retinal thickness (by SD-OCT) from BL to W10 or to discontinuation of IMP, if earlier •Change in excess CST from BL to W10 or to discontinuation of IMP, if earlier •Change in the NEI VFQ-25 score from BL to W10 or to discontinuation of IMP, if earlier •Change in the EQ-5D-3L questionnaire score from BL to W10 or to discontinuation of IMP, if earlier •Change in the EQ-5D-3L questionnaire score from BL to W10 or to discontinuation of IMP, if earlier
Time to Treatment Failure (TTF) (beyond W10) for the preventive phase is set as the secondary efficacy criterion. At any visit beyond W10 (including unscheduled visits if applicable), "Treatment Failure" is defined as Y/N by visit by meeting at least 1 of the following criteria in at least one eye (please see protocol section 2.2 Trial Endpoints). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Secondary endpoints related to the treatment of active disease: BL to W10 •Other Secondary Endpoints related to the preventive phase: beyond W10 |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 |
immunogenicity of ABY-035 |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
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 |
Germany |
|
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
|
Last Subject Last Visit (LSLV) |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |