A Study in People With Diabetic Macular Edema to Test How Well Different Doses of BI 3812465 Are Tolerated

Official title

A First-in-human, Open-label (Part 1), Randomized (Part 2), Phase I/IIa Trial to Study Safety and Tolerability of Multiple Rising Intravitreal Doses of BI 3812465 in Patients With Center-involved Diabetic Macular Edema

Overview

This study is open to adults with diabetic macular edema that involves the center of the eye. The purpose of this study is to find out how well different doses of a medicine called BI 3812465 are tolerated by people with this condition. This is the first time BI 3812465 is given to humans. This study has 2 parts. In Part 1, a small number of participants receive low, medium, or high doses of BI 3812465. The first participants to start the study get low doses of BI 3812465. Participants who start later get higher doses only if the lower doses were tolerated. In Part 2, a larger number of participants are placed into low, medium, or high dose groups. Participants in both parts of the study get BI 3812465 as injections into the back of the eye for a total of 3 eye injections. Participants are in the study for up to 7 months. During this time, they visit the study site 19 times. Where possible, some visits can be done at the participant's home instead of the study site. At study visits, the doctors check the severity of participants' eye condition and note any health problems that could have been caused by BI 3812465.

Interventions

• Biological Low dose BI 3812465
  BI 3812465
• Biological Medium dose BI 3812465
  BI 3812465
• Biological High dose BI 3812465
  BI 3812465

Primary outcome measures

• Part 1: Occurrence of dose limiting events (DLEs) from first investigational medicine product (IMP) administration until end of study (EOS) [Time frame: Up to 169 days.]
• Part 2: Occurrence of ocular adverse events (AEs) in the study eye from first IMP administration until EOS [Time frame: Up to 169 days.]

Secondary outcome measures (3)

• Occurrence of AEs from first IMP administration until EOS [Time frame: Up to 169 days.]
• Occurrence of serious adverse events (SAEs) from first IMP administration until EOS [Time frame: Up to 169 days.]
• Part 1: Occurrence of ocular AEs in the study eye from first IMP administration until EOS [Time frame: Up to 169 days.]

Eligibility criteria

Inclusion criteria

All participants, study eye:

• Center-involved diabetic macular edema (CI-DME) defined as CST ≥320 μm (micrometers) at Screening, as confirmed on spectral-domain optical coherence tomography (SD-OCT) and confirmed by the central reading center (CRC).
• Sufficiently clear ocular media, adequate pupillary dilation, and fixation, to permit quality fundus imaging.

All participants:

• Diagnosis of diabetes mellitus (DM) type 1 or type 2 under regular treatment, with glycated hemoglobin HbA1c <12%.
• Be willing and able to understand the study procedures and the risks involved.
• Signed and dated written informed consent in accordance with international council for harmonization - good clinical practices (ICH-GCP) and local legislation prior to admission to the trial and any trial related procedures.
• Age ≥18 years (or above legal age according to local legislation) at time of signing the informed consent form (ICF).
• Male or female participants

• Woman of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control
• For men, contraception (condom or complete abstinence) should be used as precaution to prevent pregnancy of a partner and/or exposure of an existing embryo or fetus.

Further inclusion criteria apply.

Exclusion criteria

All participants, study eye:

• Only one functional eye, even if that eye was otherwise eligible for the study. Fellow eye must have sufficient visual function per the investigator's medical judgment in consultation with the participant, to support the participant's daily functioning.
• Evidence of active proliferative diabetic retinopathy (PDR).
• Evidence of active retinal neovascularization (NV) clinical exam and/or Ultra-Widefield Color Fundus Photography ((UWF-)CFP) within the early treatment diabetic retinopathy study (ETDRS) 7-field, confirmed by the CRC grading. Potential participants with NV outside of the ETDRS 7-field on ultra-widefield imaging may be included in the trial if this condition, based on the assessment of the investigator, does not require acute treatment.
• Evidence of active NV of the iris (small iris tufts are not an exclusion) or in the anterior chamber angle.
• Additional eye disease in the study eye that could compromise trial participation:

• Uncontrolled glaucoma or intraocular pressure (IOP) >24 mmHg despite treatment
• History of high myopia >8 diopters in the study eye
• Anterior segment and vitreous abnormalities in the study eye that would preclude adequate detection of intraocular inflammation (IOI) or other pathologies
• Ocular conditions which, at discretion of the investigator, might interfere with the outcome of the trial.
• Previously received ocular gene therapy or cell therapy.
• Corticosteroid use locally or systemically within 1 month prior to Screening.
• Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy may be permitted, if performed more than 2 months prior to Day 1.

Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 29 centers

• Associated Retina Consultants, Ltd. — Phoenix
• Research Network Arizona — Scottsdale
• Win Retina — Arcadia
• Retina-Vitreous Associates Medical Group — Beverly Hills
• Global Research Management — Glendale
• Retina Associates of Southern California — Huntington Beach
• California Retina Consultants-Oxnard-70187 — Oxnard
• Retinal Consultants Medical Group — Sacramento
• … and 21 more centers

Puerto Rico · 1 center

• Emanuelli Research & Development Center — Arecibo

Identifiers

NCT: NCT07553429 · 1523-0001 · U1111-1316-1873

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗