A multicentric, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of COLIRIOBCN070660 administered topically in patients with moderately severe to severe non-proliferative diabetic retinopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bcn Peptides S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

17 Apr 2024 → ongoing

Decision date (initial)

2023-10-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The main objective of RETISOM is to confirm the efficacy of COLIRIOBCN070660, administered twice daily for 1 year, in reducing or arresting the number of microaneurysms in patients with moderately severe to severe NPDR

Secondary objectives 11

1. Determine the effect in reducing or arresting the number of haemorrhages (Hmas).
2. Evaluate the effect on the ETDRS severity level.
3. Evaluate the effect on the DR severity level.
4. Assess the effect on development of PDR.
5. Assess the effect on development of CI-DME.
6. Evaluate the effect on the visual acuity.
7. Evaluate the effect on visual-related quality of life.
8. Assess the effect on the vessel density.
9. Measure the effect on the Foveal Avascular Zone (FAZ).
10. Determine the incidence of vision-threatening complications due to DR (composite PDR, CI-DME or ASNV).
11. Confirm the safety of the Investigational Medicinal Product in patients with moderately severe to severe NPDR.

Conditions and MedDRA coding

Diabetic Retinopathy

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men or women with ≥ 18 years old at the time of signing the informed consent.
2. Diagnosis of diabetes mellitus (type I or type II).
3. Moderately severe or severe NPDR (ETDRS levels 47 or 53) in the Study Eye as determined by the Central Reading Centre.
4. BCVA ETDRS letter score in the Study eye of ≥60 letters (approximate Snellen equivalent of 20/63 or better).
5. Willing and able to comply with clinic visits and study-related procedures.
6. Provide a signed informed consent.

Exclusion criteria 24

1. Presence of CI-DME or other pathologies involving edema in the study eye, confirmed by evaluation of OCT images measured by the Central Reading Center (CRC) according to the following thresholds for Zeiss Cirrus: - ≥ 290 μm in women - ≥ 305 μm in men
2. Presence of retinal neovascularization in the study eye on clinical exam, by 7-field or ultra-widefield CFP.
3. Current ASNV (Anterior Segment Neovascularization), vitreous haemorrhage, or tractional retinal detachment in the study eye.
4. Any ocular condition (other than DR) in the study eye that, in the opinion of the investigator, would prevent a visual acuity improvement (e.g., clinical signs of glaucoma, clinically relevant cataract).
5. Intraocular pressure (IOP) ≥ 22 mm Hg in the study eye.
6. Presence of clinical signs of glaucoma in the study eye.
7. Evidence of active inflammation or infection in either eye, including very frequent and chronic inflammations such as blepharitis and conjunctivitis.
8. History of aphakia in the study eye.
9. History of major ocular surgery in the study eye (cataract/glaucoma/retinal detachment surgery) within prior 6 months of Screening.
10. History of YAG capsulotomy in the study eye performed within the last 2 months prior to Screening.
11. History of DME or DR treatment with laser photocoagulation in the study eye or intraocular injections of steroids or anti-VEGF medication in any of the two eyes within the prior 12 months to Screening.
12. Active glaucoma treatment with prostaglandin analogues or carbonic anhydrase inhibitors. Alfa agonists and beta blockers are allowed.
13. Patients that change diabetes mellitus treatment (including initiation of insulin treatment) in the last 4 months, or plan to do so along the study.
14. HbA1C > 10.5 % at Screening.
15. Subject with a refractive error ≥ ± 5 diopter in the Study eye.
16. Inadequate ocular media, pupil dilatation or lack of cooperation to obtain CFP, FA and OCT images with sufficient quality.
17. Renal failure, dialysis or history of renal implant.
18. Uncontrolled blood pressure (defined as systolic > 180 mm Hg and/or diastolic > 110 mmHg while patient is sitting).
19. Somatostatin treatment, for any indication, in the previous 3 months from Screening.
20. Condition or situation which may put the subject at significant risk, may confound the study results or may interfere significantly with the patient’s participation in the study.
21. Pregnant or nursing or intending to become pregnant along the study.
22. Hypersensitivity to the active substance to be tested or to any of the excipients.
23. Known allergy to fluorescein dye.
24. Participation in an investigational study within 30 days prior to Screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction or arrest of the microvascular impairment, based on the quantification of the number of microaneurysms in the central retinal field in patients with moderately severe to severe NPDR assessed by FA.

Secondary endpoints 13

1. Change on number of haemorrhages (Hmas) in the central retinal field by FA.
2. Change on the number of MAs and Hmas in the central field by CFP.
3. Change on ETDRS severity level assessed by 7-field or ultra-widefield CFP.
4. Changes on Retinal thickness assessed by OCT.
5. Changes on Vessel density assessed by OCTA.
6. Changes on Foveal Avascular Zone (FAZ) growth assessed by OCTA.
7. Changes on visual acuity assessed (BCVA) using the 4-meter ETDRS protocol.
8. Proportion of patients who change by ≥ 2 steps in the ETDRS severity scale.
9. Proportion of patients who change on DR severity level assessed by 7-field or ultra-widefield CFP.
10. Incidence and time to development of proliferative diabetic retinopathy (PDR) assessed by 7-field or ultra-widefield CFP.
11. Incidence and time to development of Central-Involved Diabetic Macular Edema (CI-DME) assessed by OCT.
12. Incidence and time to development of vision-threating complications due to DR (composite of PDR, CI-DME or anterior segment neovascularization (ASNV)) assessed by 7-field or ultra-widefield CFP, OCT, slit lamp examination or indirect ophthalmoscopy.
13. Changes on DR biomarkers

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bcn Peptides S.A.

Sponsor organisation

Bcn Peptides S.A.

Address

Poligono Industrial Els Vinyets Els Fogars Sector II

City

Sant Quinti De Mediona

Postcode

08777

Country

Spain

Scientific contact point

Organisation

Bcn Peptides S.A.

Contact name

CT Info Desk

Public contact point

Organisation

Bcn Peptides S.A.

Contact name

CT Info Desk

Locations

1 EU/EEA country · 10 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 14 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