Clinical trial NCT06321302: A Study to Test Whether BI 764524 Helps People With an Eye Condition Called Diabetic Retinopathy
Official title: CRIMSON: A Multicentre, Randomised, Sham-controlled (and Active Controlled in the USA), Double-masked, 72-week Trial to Study the Safety, Tolerability, Pharmacokinetics, and Efficacy of 3 Dosing Regimens of Intravitreal BI 764524 in Patients With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Retinopathy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2024-03-20
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is open to adults with diabetic retinopathy. People who have non-proliferative diabetic retinopathy of moderate or high severity can join the study.

The purpose of this study is to find out whether a medicine called BI 764524 helps people with diabetic retinopathy. The study also aims to find a suitable treatment plan for BI 764524. Participants are put into 5 groups by chance. Participants in groups 1, 2, and 3 get BI 764524. Over 1 year, they get a different number of injections of the same dose of BI 764524 injected into 1 eye. During some visits, participants may get a sham control, which is done like an eye injection but without a needle, so that participants will not know how many injections of BI 764524 they received. Participants in group 4 only get a sham control. Participants in group 5 (only in the USA) get aflibercept or sham injections during some visits. Aflibercept is a medicine already used to treat diabetic retinopathy.

Participants are in the study for one and a half years. During this time, they visit the study site at least 16 times. During this time, doctors regularly do eye exams and visual tests to assess the severity of participants' eye condition. After 1 year of treatment, researchers look at the number of participants with eye improvements. To do so, they compare eye damage and certain severe eye problems between the groups of participants. The doctors also regularly check participants' health and take note of any unwanted effects.


Eligibility criteria: General inclusion criteria

* Diagnosis of DM under regular treatment with Haemoglobin A1c (HbA1c) (glycated haemoglobin) (HbA1c) \<12%
* Age ≥18 years at time of signing Informed Consent Form

Ocular inclusion criteria: study eye

* Moderately severe to severe non-proliferative diabetic retinopathy (NPDR) (Diabetic Retinopathy Severity Scale (DRSS) 47 to 53) based on early treatment diabetic retinopathy study (ETDRS) 7-field grading as confirmed by the central reading centre (CRC) at screening
* Presence of retinal non-perfusion (RNP) as assessed by ultra-widefield fluorescein angiography (UWF-FA) defined as an area ≥12.5 square millimeter (mm²) (approximately ≥5 disc areas) within a circular area with a 17.5 millimeter (mm) radius centred to the fovea as confirmed by the CRC at screening
* Visual acuity: best corrected visual acuity (BCVA) letter score of ≥49 letters (approximate Snellen equivalent of 20/100 or better) using ETDRS chart at starting distance of 4 meter (m) at screening
* Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging

Main exclusion criteria in study eye:

* Evidence of active retinal neovascularisation (NV) on clinical exam and/or ultra-widefield colour fundus photography (UWF-CFP) within the ETDRS 7-field, confirmed by the CRC grading

  -- Neovascularisations outside of the ETDRS 7-field on ultra-widefield imaging may be included 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
* Prior pan-retinal photocoagulation (PRP) (defined as ≥100 burns placed previously outside of the posterior pole)
* CI-DME, defined as a central subfield thickness (CST) ≥320 micrometer (μm) (men)/305 μm (women), measured by Heidelberg Spectralis optical coherence tomography (OCT)), in the study eye as confirmed by the CRC at screening
* Previous treatment in the study eye for NPDR and/or diabetic macular edema (DME) with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) (including anti-VEGF/Ang2) drugs within 6 months prior to Day 1. The number of patients with history of an IVT anti-VEGF treatment is limited to approximately 50 randomised patients. Once this number has been achieved, any patients with previous IVT treatment will be excluded
* Any previous IVT treatment other than anti-VEGF, including steroids
* Refractive error of more than -8 dioptres of myopia (spherical equivalent) in the study eye. For patients having undergone refractive or cataract surgery in the study eye, the preoperative refractive error should be used.
* Any concurrent or past ocular condition in the study eye which, in the judgement of the investigator, could:

  * Require medical or surgical intervention during the study period to prevent or treat vision loss (e.g. advanced cataract, history of retinal detachment or macular hole (Stage 3 or 4) in the study eye)
  * Could likely contribute to a significant loss of BCVA during the study period if left untreated (e.g. advanced epiretinal membrane and/or vitreomacular traction, active or history of optic neuritis in either eye)
  * Contraindicate the use of the investigational drug, or may render the patient at high risk for treatment complications (e.g. active infectious or non-infectious conjunctivitis/keratitis in either eye; history of recurrent infectious or inflammatory ocular disease in either eye (e.g. uveitis)
  * May affect interpretation of the study results (e.g. central atrophy of the retinal pigment epithelium or photoreceptors; age-related macular degeneration, hereditary retinal degenerative diseases, myopic macular degeneration, past, current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. deferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol); history of central serous chorioretinopathy, ischemic optic neuropathy or retinal vascular occlusion

Primary outcomes:
measure: Occurrence of a ≥2-step improvement compared with baseline in Diabetic Retinopathy Severity Scale (DRSS) level in the study eye at Week 52
timeFrame: At baseline and at Week 52
Secondary outcomes:
measure: Occurrence of vision threatening complications (VTC)s in the study eye between baseline and Week 52
timeFrame: At baseline and at Week 52
measure: Absolute change from baseline of best corrected visual acuity (BCVA) [early treatment diabetic retinopathy study (ETDRS) letters] in the study eye at Week 52
timeFrame: At baseline and at Week 52
measure: Absolute change from baseline of central retinal thickness [μm], as assessed by spectral domain optical coherence tomography (SD-OCT), in the study eye at Week 52
timeFrame: At baseline and at Week 52
measure: Occurrence of a ≥2-step worsening of Diabetic Retinopathy Severity Scale (DRSS) in the study eye between baseline and Week 52
timeFrame: At baseline and at Week 52
measure: Occurrence of proliferative diabetic retinopathy (PDR) and/or anterior segment neovascularisation (NV) in the study eye between baseline and Week 52
timeFrame: At baseline and at Week 52
measure: Occurrence of centre-involved diabetic macular edema (CI-DME) in the study eye between baseline and Week 52
timeFrame: At baseline and at Week 52
measure: Occurrence of drug-related adverse events (AEs) between baseline and end of study (EOS)
timeFrame: up to 72 weeks
measure: Occurrence of ocular AEs in the study eye between baseline and EOS
timeFrame: up to 72 weeks
measure: Occurrence of ocular AEs of special interest in the study eye between baseline and EOS
timeFrame: up to 72 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants, Ltd.
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants-Bakersfield-65523
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Glendale
country: United States
facility: Lugene Eye Institute
state: California
city: Huntington Beach
country: United States
facility: Retina Associates of Southern California
state: California
city: Los Angeles
country: United States
facility: American Institute of Research, Inc
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical Group Inc
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants-Santa Maria-65510
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates - Walnut Creek
state: California
city: Lakewood
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England, PC
state: Connecticut
city: Jacksonville
country: United States
facility: Florida Retina Institute
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Stuart
country: United States
facility: East Florida Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: 'Aiea
country: United States
facility: Retina Consultants Of Hawaii
state: Hawaii
city: Southaven
country: United States
facility: Deep Blue Retina Clinical Research PLLC
state: Mississippi
city: Teaneck
country: United States
facility: NJRetina
state: New Jersey
city: Liverpool
country: United States
facility: Retina Vitreous Surgeons of Central NY, PC
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Portland
country: United States
facility: EyeHealth Northwest
state: Oregon
city: Ladson
country: United States
facility: Charleston Neuroscience Institute - Ladson
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Retina
state: Tennessee
city: Austin
country: United States
facility: Retina Research Center, PLLC
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, PA
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston, PA-The Woodlands-66484
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Neubrandenburg
country: Germany
facility: Dietrich-Bonhoeffer-Klinikum
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: Budapest Retina Associations Ltd.
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-Pest Hospital
city: Debrecen
country: Hungary
facility: University Debrecen Hospital
city: Pecs
country: Hungary
facility: Ganglion Orvosi Kozpont
city: Zala
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Campobasso
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: IRCCS San Raffaele
city: Roma
country: Italy
facility: IRCCS Fondazione Bietti
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Torrette Di Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Akita
country: Japan
facility: Akita University Hospital
city: Amagasaki
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center
city: Fukuoka
country: Japan
facility: Hayashi Eye Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Hachioji-shi
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Kobe
country: Japan
facility: Kobe University Hospital
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
city: Meguro-ku
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Bydgoszcz
country: Poland
facility: Klinika Okulistyczna
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka-Lens Sp. z o.o.
city: Walbrzych
country: Poland
facility: Centrum Medyczne Piasta 47 sp. z o.o.
city: Warszawa
country: Poland
facility: Warsaw Ophthalmology Hospital
city: Wroclaw
country: Poland
facility: 4. Military Clinical Hospital with Polyclinic SP ZOZ
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research & Development Center
city: Barcelona
country: Spain
facility: University Hospital of Bellvitge
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sant Cugat del Vallés
country: Spain
facility: Hospital Universitari General de Catalunya
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Colchester
country: United Kingdom
facility: East Suffolk and North Essex NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: London
country: United Kingdom
facility: Western Eye Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
References: