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

NCT04002310 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1418-00012018-004125-92
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 13

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.

Conditions

Macular Degeneration

Outcome Measures

Primary Outcomes (2)

• SRD Part: Number of Patients With Ocular (in the Study Eye) or Systemic Dose Limiting Events (DLEs)

  SRD part: Number of patients with ocular or systemic DLEs from drug administration. Systemic DLEs were defined as drug-related adverse events (AEs), as defined by the investigator, of moderate or severe intensity on the Common terminology criteria for adverse events (CTCAE) scale, and included diarrhea, cough, or patient-reported paraesthesia, dysgeusia, taste abnormality, taste disorder, or hyposmia. Single rising dose (SRD) part.

  From drug administration until end of trial, up to 100 days.

• MD Part: Number of Patients With Drug Related Adverse Events (AEs)

  Number of patients with drug-related adverse events (AEs). Multiple dose (MD) part.

  From drug administration until end of trial, up to 155 days

Secondary Outcomes (8)

• SRD Part: Number of Patients With Drug-related Adverse Events (AEs)

  From drug administration until end of trial, up to 100 days.

• SRD Part: Number of Patients With Any Ocular Adverse Events (AEs) in the Study Eye

  From drug administration until end of trial, up to 100 days.

• SRD Part: Maximum Serum Concentration of BI 754132 After a Single Intravitreal Dose (Cmax)

  At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.

• SRD Part: Area Under the Concentration-time Curve of BI 754132 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

  At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.

• SRD Part: Time From Dosing to Maximum Serum Concentration of BI 754132 (Tmax)

  At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.

Study Arms (5)

0.3 mg BI 754132 - SRD part

EXPERIMENTAL

0.3 milligram (mg) BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. Single rising dose (SRD) part.

Drug: BI 754132

1 mg BI 754132 - SRD part

EXPERIMENTAL

1 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.

Drug: BI 754132

3 mg BI 754132 - SRD part

EXPERIMENTAL

3 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.

Drug: BI 754132

6 mg BI 754132 - SRD part

EXPERIMENTAL

6 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.

Drug: BI 754132

6 mg BI 754132 - MD part

EXPERIMENTAL

6 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as 3 injections, each separated by 4 weeks (that is, Day 1, Day 29 and Day 57). Multiple dose.

Drug: BI 754132

Interventions

BI 754132 DRUG

One single injection

0.3 mg BI 754132 - SRD part; 1 mg BI 754132 - SRD part; 3 mg BI 754132 - SRD part; 6 mg BI 754132 - MD part; 6 mg BI 754132 - SRD part

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (13)

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Center for Retina and Macular Disease

Winter Haven, Florida, 33880, United States

Location

Southeast Retina Center, PC

Augusta, Georgia, 30909, United States

Location

Western Carolina Retinal Associate PA

Asheville, North Carolina, 28803, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Bristol Eye Hospital

Bristol, BS1 2LX, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L69 3GA, United Kingdom

Location

Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Limitations and Caveats

The trial was terminated prematurely based on a negative benefit-risk assessment, which was based on the analysis of the safety data during the trial.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

18002430127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: June 28, 2019
• Study Start: July 26, 2019
• Primary Completion: August 9, 2022
• Study Completion: August 9, 2022
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); US (8)