A Multicentre Study to Evaluate the Safety and Efficacy of the Eye Implant ILUVIEN® in Children with non-infectious uveitis affecting the posterior segment of the eye

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alimera Sciences Europe Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

17 Apr 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Alimera Sciences Europe Limited

External identifiers

EU CT number

2023-509469-19-00

EudraCT number

2022-001622-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate safety and efficacy of ILUVIEN® 190μg in paediatric subjects with recurrent non-infectious uveitis affecting the posterior segment of the eye

Secondary objectives 3

1. To assess the incidence of recurrence of non-infectious uveitis affecting the posterior segment in the study eye
2. To evaluate the incidence and onset of secondary lens opacity and extraction
3. To assess the incidence of secondary intraocular pressure (IOP) elevation

Conditions and MedDRA coding

Non-Infectious Uveitis affecting the posterior segment

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000801-PIP03-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Males and females of ≥6 and <18 years of age at time of consent
2. Non-infectious uveitis affecting the posterior segment of the study eye with a history of recurrence ≥1 per year as assessed by the Investigator
3. Uveitis in the study eye not adequately controlled by the preferred standard of care due to intolerable adverse effects or poor response, in the judgment of the Investigator
4. Treatment with systemic corticosteroid or other systemic therapies given for at least 3 months within the previous 12 months prior to Day 1
5. The degree of inflammation with anterior chamber cells ≥ Grade 1 and/or vitreous haze of ≥ Grade 1 and/or evidence of macular oedema in the study eye considered to be caused by recurrent uveitis
6. Visual acuity of study eye is at least 35 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart
7. No evidence of medically unstable systemic disease defined as any systemic disease requiring a change (increase or decrease) in systemic treatment in the 90 days prior to Day 1
8. Ability and willingness to comply with the treatment and follow-up procedures
9. No expectation that the subject will be moving out of the area of the clinical centre to an area not covered by another clinical centre during the next 36 months
10. Subject is not planning to undergo elective ocular surgery during the trial
11. Presence of a signed written informed consent form from the subject or subject's legal representative, and/or a signed info assent from subject in accordance with local legal requirements.

Exclusion criteria 33

1. History of intraocular surgery in the study eye within 90 days of the screening visit
2. Hypersensitivity to FA or any component of ILUVIEN
3. History of any form of glaucoma or ocular hypertension in study eye, unless study eye has been previously treated with an incisional IOPlowering surgical procedure at least 90 days prior to the screening visit and that procedure has resulted in stable IOP in the normal range (10- 21 mmHg))
4. Increased intraocular pressure >25 mmHg or that required treatment including increases in medications, surgery (other than drainage surgery), or hospitalisations, within 4 weeks prior to baseline that, in the opinion of the Investigator, would pose an unacceptable risk to the patient participating in the study
5. Best corrected visual acuity (BCVA) < 20/200 in the study eye at screening and Day 1
6. History of posterior uveitis only that was not accompanied by vitritis or macular oedema
7. History of iritis only and no vitreous cells, anterior chamber cells (ACC), or vitreous haze
8. Uveitis with infectious aetiology
9. Mycobacterial uveitis or chorioretinal changes of either eye which, in the opinion of the Investigator, resulted from infectious mycobacterial uveitis
10. Vitreous haemorrhage
11. Intraocular inflammation associated with a condition other than non-infectious uveitis (e.g., intraocular lymphoma)
12. Ocular malignancy in either eye, including choroidal melanoma
13. Toxoplasmosis scar in study eye; or scar related to previous viral retinitis
14. Previous viral retinitis
15. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and mycobacterial infections of the eye or fungal diseases of ocular structure
16. Media opacity precluding evaluation of retina and vitreous
17. Peripheral retinal detachment and/or vitreoretinal traction in area of area of insertion
18. Prior administration of intravitreal Ozurdex within 6 months of the screening visit
19. Prior administration of fluocinolone intravitreal implant within 3 years of the screening visit in the study eye
20. Viral corneal pathology in the study eye
21. Moderate to severe dry eye in the study eye
22. Ocular or adnexal infections or infectious uveitis in the study eye
23. Chronic hypotony (< 6 mmHg)
24. Capsulotomy in study eye within 30 days prior to Day 1
25. Subjects requiring chronic systemic or inhaled corticosteroid therapy (>0.15 mg/kg daily) or systemic immunosuppressive therapy for autoimmune conditions other than Juvenile Idiopathic Arthritis, Blau syndrome, Idiopathic Chronic Anterior Uveitis, Intermediate Uveitis, Idiopathic Panuveitis
26. History of certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to Day 1
27. Systemic infection within 30 days prior to Day 1
28. Any severe acute or chronic medical or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the Investigator, could make the subject inappropriate for entry into this study
29. Any other systemic or ocular condition which, in the judgment of the Investigator, could make the subject inappropriate for entry into this study
30. Treatment with an investigational drug or device within 3 months prior to Day 1
31. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 14 days prior to study Day 1 until the End of Study (Month 36).
32. Any persons with a dependent relationship to the sponsor, the investigational site or the Investigator.
33. Any persons held in an institution by a government or judicial order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Treatment success based on: 1. Absence of cystoid macular oedema on Optical Coherence Tomography AND 2. A decrease from baseline in vitreous haze grade ≥2 steps, or absence of vitreous haze
2. Rate of cataract formation
3. Rate of IOP elevation (Change from baseline in IOP and incidence of significant changes in IOP, including: IOP>21 mmHg, IOP>25 mmHg IOP>30 mmHg, increases from baseline of 10 mmHg or more).

Secondary endpoints 16

1. Absence of cystoid macular oedema and decrease from baseline in vitreous haze grade of ≥2 steps, or absence of vitreous haze at completion of the study
2. Uveitis recurrence rate following treatment, compared to the uveitis recurrence rate over the 12 months prior to enrolment
3. The incidence of recurrence of non-infectious uveitis affecting the posterior segment in the study eye and in the fellow eye after receiving study treatment
4. The time to recurrence of non-infectious uveitis affecting the posterior segment in the study eye
5. Change in macular oedema
6. Change in Best Corrected Visual Acuity
7. Change in vitreous haze
8. Change in anterior chamber cell grade
9. Incidence of secondary increase in IOP
10. Incidence of secondary increase in IOP requiring surgical intervention
11. Incidence and onset of secondary lens opacity and extraction
12. Number of adjunctive treatments required to treat recurrences of uveitis
13. Presence of active chorioretinal and retinal vascular lesions
14. Incidence of ocular infection
15. Change from baseline in cup-to-disc ratio
16. Incidence of ocular and non-ocular adverse events (AEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alimera Sciences Europe Limited

Sponsor organisation

Alimera Sciences Europe Limited

Address

Block C, 77 Sir John Rogerson's Quay 77 Sir John Rogerson's Quay

City

Dublin 2

Postcode

D02 VK60

Country

Ireland

Scientific contact point

Organisation

Alimera Sciences Europe Limited

Contact name

Alimera Sciences Europe Limited

Public contact point

Organisation

Alimera Sciences Europe Limited

Contact name

Alimera Sciences Europe Limited

Third parties 2

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications