Efficacy of Topical Somatostatin (COLIRIOBCN070660) in Moderately Severe to Severe Non-Proliferative Diabetic Retinopathy: A Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2023-505791-30-01
Protocol: RETISOM
Sponsor: Bcn Peptides S.A.

Trial statistics

science

test molecules

location_city

research sites

public

country

medical_information

disease

person_search

investigators

Diseases & Conditions

Diabetic retinopathy

Objectives

The primary objective of this multicentric, randomized, double-blind, placebo-controlled trial is to confirm the efficacy of **COLIRIOBCN070660**, administered topically twice daily for one year, in reducing or arresting the number of microaneurysms in patients with moderately severe to severe non-proliferative **diabetic retinopathy** (NPDR). This is clinically relevant as microaneurysms are a hallmark of diabetic retinopathy progression, and their reduction could potentially slow disease progression and preserve vision.

Secondary objectives include:

Determining the effect in reducing or arresting the number of haemorrhages.
Evaluating the effect on the ETDRS severity level and DR severity level.
Assessing the effect on the development of proliferative diabetic retinopathy (PDR) and clinically significant diabetic macular edema (CI-DME).
Evaluating the effect on visual acuity and visual-related quality of life.
Assessing the effect on vessel density and measuring the effect on the Foveal Avascular Zone (FAZ).
Determining the incidence of vision-threatening complications due to diabetic retinopathy, including composite PDR, CI-DME, or anterior segment neovascularization (ASNV).
Confirming the safety of the investigational medicinal product in patients with moderately severe to severe NPDR.

Participants

The clinical trial focuses on individuals diagnosed with **Diabetic Retinopathy**, specifically those with moderately severe to severe non-proliferative diabetic retinopathy (NPDR). The study population includes both male and female participants aged 18 years and older. Participants are required to have a diagnosis of diabetes mellitus, either type I or type II, and must exhibit a BCVA ETDRS letter score in the study eye of 60 letters or more, which is approximately equivalent to a Snellen score of 20/63 or better. The trial does not involve a vulnerable population. Participants are expected to be willing and able to comply with clinic visits and study-related procedures. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Key inclusion criteria include the ability to provide signed informed consent and the determination of NPDR severity by the Central Reading Centre. The selection process for the trial population is not detailed in the provided data.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy of COLIRIOBCN070660, an **eye drop** formulation containing **somatostatin**, in patients with moderately severe to severe non-proliferative **diabetic retinopathy**. The trial aims to confirm the efficacy of the treatment in reducing or arresting the number of microaneurysms over a period of one year. Participants will be randomly assigned to receive either the active treatment or a placebo, administered twice daily. The trial is expected to commence recruitment on September 1, 2023, and conclude by May 1, 2025, with a total duration of approximately 20 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥18 years), diagnosis of diabetes mellitus (type I or II), and specific visual acuity and retinopathy severity levels. Following successful screening, participants will be enrolled and randomized into the study. Regular follow-up visits will be scheduled to monitor the treatment's effects and assess primary and secondary endpoints, including the reduction of microvascular impairment and changes in retinal thickness and vessel density. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted.

The expected length of participant involvement is 12 months, corresponding to the treatment period. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial's primary endpoint focuses on the reduction or arrest of microvascular impairment, while secondary endpoints include various measures of retinal health and visual function. The study is categorized as a confirmatory Phase II-III clinical trial, emphasizing its role in validating the treatment's efficacy and safety in a controlled setting.

Treatment

The clinical trial involves the administration of **COLIRIOBCN070660**, an experimental medication formulated as **eye drops**. The active substance in this formulation is **somatostatin**, a protein of non-human origin. The eye drops are intended for **ocular use** and are administered topically. The dosage regimen involves a maximum daily dose of 160 micrograms, with the treatment period extending up to 12 months. The administration frequency is twice daily, ensuring consistent exposure to the active compound. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** comparator, named **PLACEBO COLIRIOBCN070660**, is utilized in this study. The placebo is designed to mimic the experimental eye drops in appearance and administration method but does not contain the active substance, somatostatin. The placebo is administered under the same conditions as the experimental treatment, ensuring the integrity of the double-blind study design. The use of a placebo allows for the assessment of the true efficacy of COLIRIOBCN070660 by providing a baseline for comparison.

Efficacy

The efficacy of the investigational product, COLIRIOBCN070660, in the treatment of moderately severe to severe non-proliferative diabetic retinopathy (NPDR) will be assessed through a multicentric, randomized, double-blind, placebo-controlled trial. The primary endpoint for evaluating efficacy is the reduction or arrest of microvascular impairment, specifically quantified by the number of microaneurysms in the central retinal field, as assessed by fluorescein angiography (FA). Secondary endpoints include the number of hemorrhages in the central retinal field, the severity level of diabetic retinopathy (DR) assessed by 7-field color fundus photography (CFP), and the presence of proliferative diabetic retinopathy (PDR) and central-involved diabetic macular edema (CI-DME) assessed by spectral domain optical coherence tomography (SD-OCT).

Additional secondary endpoints involve the assessment of central retinal thickness, vessel density, and foveal avascular zone (FAZ) using optical coherence tomography angiography (OCTA). The appearance of vision-threatening complications due to DR will be evaluated through a composite outcome of PDR, CI-DME, vitreous hemorrhage, or tractional retinal detachment, assessed by 7-field CFP, SD-OCT, slit lamp examination, or indirect ophthalmoscopy. Best corrected visual acuity (BCVA) will be measured using the 4-meter ETDRS protocol, and visual-related quality of life will be assessed using the Visual Function Questionnaire 25 (VFQ-25). Blood biomarkers related to DR will also be evaluated if relevant biomarkers are identified through a bibliographic review.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

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

cancel

Exclusion Criteria

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
Presence of retinal neovascularization in the study eye on clinical exam, by 7-field or ultra-widefield CFP.
Current ASNV (Anterior Segment Neovascularization), vitreous haemorrhage, or tractional retinal detachment in the study eye.
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).
Intraocular pressure (IOP) ≥ 22 mm Hg in the study eye.
Presence of clinical signs of glaucoma in the study eye.
Evidence of active inflammation or infection in either eye, including very frequent and chronic inflammations such as blepharitis and conjunctivitis.
History of aphakia in the study eye.
History of major ocular surgery in the study eye (cataract/glaucoma/retinal detachment surgery) within prior 6 months of Screening.
History of YAG capsulotomy in the study eye performed within the last 2 months prior to Screening.
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.
Active glaucoma treatment with prostaglandin analogues or carbonic anhydrase inhibitors. Alfa agonists and beta blockers are allowed.
Patients that change diabetes mellitus treatment (including initiation of insulin treatment) in the last 4 months, or plan to do so along the study.
HbA1C > 10.5 % at Screening.
Subject with a refractive error ≥ ± 5 diopter in the Study eye.
Inadequate ocular media, pupil dilatation or lack of cooperation to obtain CFP, FA and OCT images with sufficient quality.
Renal failure, dialysis or history of renal implant.
Uncontrolled blood pressure (defined as systolic > 180 mm Hg and/or diastolic > 110 mmHg while patient is sitting).
Somatostatin treatment, for any indication, in the previous 3 months from Screening.
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.
Pregnant or nursing or intending to become pregnant along the study.
Hypersensitivity to the active substance to be tested or to any of the excipients.
Known allergy to fluorescein dye.
Participation in an investigational study within 30 days prior to Screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.