Clinical trial NCT04002310: A Study to Test How Well Different Doses of BI 754132 Are Tolerated in Patients With an Advanced Form of Age-related Macular Degeneration Called Geographic Atrophy
Official title: Safety, Tolerability and Pharmacokinetics of Single Rising Intravitreal Doses and Multiple Intravitreal Dosing of BI 754132 in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration (Open Label, Non-randomized, Uncontrolled).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Macular Degeneration
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-06-28
Enrollment: 18
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a study in adults with geographic atrophy, an advanced form of age-related macular degeneration. The purpose of this study is to find out how well different doses of BI 754132 are tolerated.

The participants are in the study for about 4 months. During this time, they visit the study site about 10 times. Participants receive 1 injection of BI 754132 directly into one of the eyes affected by geographic atrophy. In this study, BI 754132 is given to humans for the first time.

The doctors compare how well participants tolerate the different doses of BI 754132. The doctors also regularly check the general health of the participants.


Eligibility criteria: Inclusion criteria:

- Men and women with Geographic Atrophy (GA) secondary to Age-related Macular Degeneration (AMD): For the SRD part, the GA lesion in the study eye must be ≥ 1.9 mm2 disc area in size (approximately ≥ 0.75 disc area in size); For the MD part the total GA lesion size in the study eye must be ≥ 7.5 mm2 (approximately ≥ 3 disc area in size)

* Fellow eye is not required to have GA
* Best Corrected Visual Acuity (BCVA):

  * SRD part: BCVA of 20/100 to 20/400 Snellen (corresponding to 19 to 53 letters in the ETDRS chart) in the study eye equivalent measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol
  * MD part: BCVA score of ≤53 letters (Snellen equivalent of 20/100) in the study eye
* Age ≥ than 50 years
* Best-corrected VA in the non-study eye must have a better best-corrected VA compared to the study-eye
* Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
* Signed informed consent consistent with International Council on Harmonisation Good Clinical Practice (ICH GCP) guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions
* Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order

Exclusion criteria

* GA in either eye because of causes other than AMD
* History of choroidal neovascularization (CNV) in the study eye and in the fellow eye
* Previous treatment in the study eye for GA secondary to AMD within 6 months prior to screening visit (ongoing therapy with vitamin and mineral supplements is allowed)
* Additional eye disease in the study eye that could compromise

  * best corrected VA (BCVA) with visual field loss,
  * uncontrolled glaucoma intraocular pressure (IOP\>24),
  * clinically significant diabetic maculopathy,
  * history of ischemic optic neuropathy or retinal vascular occlusion,
  * symptomatic vitreomacular traction,
  * genetic disorders such as retinitis pigmentosa);
  * history of high myopia \> 8 diopters in the study eye and
  * anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with Spectral Domain Optical Coherence Tomography (SD-OCT)
* Any prior intraocular surgery in the study eye other then uneventful lens replacement for cataract within 3 months prior to screening
* Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, more than 3 month prior to enrollment in the study eye
* Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol)
* Significant disease or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following:

  * Put the patient at risk because of participation in the study
  * Influence the results of the study,
  * Cause concern regarding the patient's ability to participate in the study, e.g. cardiac (including tachycardia), gastro-intestinal, hepatic, renal, metabolic, dermatologic, neurological, haematological, oncological and psychiatric.
* Patients with malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed.
* Known hypersensitivity to any of the ingredients used in the Investigational Medical Product (IMP) formulation, or any of the medications used
* Active intraocular inflammation in the study eye
* Active infectious conjunctivitis in either eye
* Further exclusion criteria apply

Primary outcomes:
measure: SRD Part: Number of Patients With Ocular (in the Study Eye) or Systemic Dose Limiting Events (DLEs)
timeFrame: From drug administration until end of trial, up to 100 days.
measure: MD Part: Number of Patients With Drug Related Adverse Events (AEs)
timeFrame: From drug administration until end of trial, up to 155 days
Secondary outcomes:
measure: SRD Part: Number of Patients With Drug-related Adverse Events (AEs)
timeFrame: From drug administration until end of trial, up to 100 days.
measure: SRD Part: Number of Patients With Any Ocular Adverse Events (AEs) in the Study Eye
timeFrame: From drug administration until end of trial, up to 100 days.
measure: SRD Part: Maximum Serum Concentration of BI 754132 After a Single Intravitreal Dose (Cmax)
timeFrame: At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
measure: SRD Part: Area Under the Concentration-time Curve of BI 754132 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
measure: SRD Part: Time From Dosing to Maximum Serum Concentration of BI 754132 (Tmax)
timeFrame: At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
measure: MD Part: Trough Levels of BI 754132 Before Second Administration (Cmin,1)
timeFrame: Up to 29 days.
measure: MD Part: Trough Levels of BI 754132 Before Third Administration (Cmin,2)
timeFrame: Up to 57 days.
measure: MD Part: Plasma Concentration of BI 754132 4, 8 and 14 Weeks After the Third Administration
timeFrame: At Day 85, 113 and Day 155.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Asheville
country: United States
facility: Western Carolina Retinal Associate PA
state: North Carolina
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: