Back to resultsA 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
Primary Purpose
Macular Degeneration
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BI 754132
Sponsored by
About this trial
This is an interventional treatment trial for Macular Degeneration
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
Sites / Locations
- Retina-Vitreous Associates Medical Group
- Retina Specialty Institute
- Center for Retina and Macular Disease
- Southeast Retina Center, PC
- Western Carolina Retinal Associate PA
- Mid Atlantic Retina
- Retina Consultants of Texas
- Retina Foundation of the Southwest
- Bristol Eye Hospital
- Royal Liverpool University Hospital
- Moorfields Eye Hospital
- Royal Victoria Infirmary
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
0.3 mg BI 754132 - SRD part
1 mg BI 754132 - SRD part
3 mg BI 754132 - SRD part
6 mg BI 754132 - SRD part
6 mg BI 754132 - MD part
Arm Description
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
MD Part: Number of Patients With Drug Related Adverse Events (AEs)
Number of patients with drug-related adverse events (AEs). Multiple dose (MD) part.
Secondary Outcome Measures
SRD Part: Number of Patients With Drug-related Adverse Events (AEs)
Number of patients with drug-related AEs. Single rising dose (SRD) part.
SRD Part: Number of Patients With Any Ocular Adverse Events (AEs) in the Study Eye
Number of patients with any ocular adverse events in the study eye. Single rising dose (SRD) part.
SRD Part: Maximum Serum Concentration of BI 754132 After a Single Intravitreal Dose (Cmax)
Maximum serum concentration of BI 754132 after a single intravitreal dose (Cmax). Single rising dose (SRD) part.
SRD Part: Area Under the Concentration-time Curve of BI 754132 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 754132 in serum over the time interval from 0 extrapolated to infinity (AUC0-∞). Singe rising dose (SRD) part.
SRD Part: Time From Dosing to Maximum Serum Concentration of BI 754132 (Tmax)
Time from dosing to maximum serum concentration of BI 754132 (tmax). Single rising dose (SRD part).
MD Part: Trough Levels of BI 754132 Before Second Administration (Cmin,1)
Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,1 (trough levels of BI 754132 before second administration). Multiple dose (MD) part.
MD Part: Trough Levels of BI 754132 Before Third Administration (Cmin,2)
Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,2 (trough levels of BI 754132 before third administration). Multiple dose (MD) part.
MD Part: Plasma Concentration of BI 754132 4, 8 and 14 Weeks After the Third Administration
Plasma concentration of BI 754132 4, 8 and 14 weeks after the third administration. Multiple dose (MD) part.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04002310
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
The trial was discontinued in the interests of patients considering benefit/risk balance.
Study Start Date
July 26, 2019 (Actual)
Primary Completion Date
August 9, 2022 (Actual)
Study Completion Date
August 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
0.3 mg BI 754132 - SRD part
Arm Type
Experimental
Arm Description
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.
Arm Title
1 mg BI 754132 - SRD part
Arm Type
Experimental
Arm Description
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.
Arm Title
3 mg BI 754132 - SRD part
Arm Type
Experimental
Arm Description
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.
Arm Title
6 mg BI 754132 - SRD part
Arm Type
Experimental
Arm Description
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.
Arm Title
6 mg BI 754132 - MD part
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BI 754132
Intervention Description
One single injection
Primary Outcome Measure Information:
Title
SRD Part: Number of Patients With Ocular (in the Study Eye) or Systemic Dose Limiting Events (DLEs)
Description
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.
Time Frame
From drug administration until end of trial, up to 100 days.
Title
MD Part: Number of Patients With Drug Related Adverse Events (AEs)
Description
Number of patients with drug-related adverse events (AEs). Multiple dose (MD) part.
Time Frame
From drug administration until end of trial, up to 155 days
Secondary Outcome Measure Information:
Title
SRD Part: Number of Patients With Drug-related Adverse Events (AEs)
Description
Number of patients with drug-related AEs. Single rising dose (SRD) part.
Time Frame
From drug administration until end of trial, up to 100 days.
Title
SRD Part: Number of Patients With Any Ocular Adverse Events (AEs) in the Study Eye
Description
Number of patients with any ocular adverse events in the study eye. Single rising dose (SRD) part.
Time Frame
From drug administration until end of trial, up to 100 days.
Title
SRD Part: Maximum Serum Concentration of BI 754132 After a Single Intravitreal Dose (Cmax)
Description
Maximum serum concentration of BI 754132 after a single intravitreal dose (Cmax). Single rising dose (SRD) part.
Time Frame
At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
Title
SRD Part: Area Under the Concentration-time Curve of BI 754132 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Description
Area under the concentration-time curve of BI 754132 in serum over the time interval from 0 extrapolated to infinity (AUC0-∞). Singe rising dose (SRD) part.
Time Frame
At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
Title
SRD Part: Time From Dosing to Maximum Serum Concentration of BI 754132 (Tmax)
Description
Time from dosing to maximum serum concentration of BI 754132 (tmax). Single rising dose (SRD part).
Time Frame
At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
Title
MD Part: Trough Levels of BI 754132 Before Second Administration (Cmin,1)
Description
Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,1 (trough levels of BI 754132 before second administration). Multiple dose (MD) part.
Time Frame
Up to 29 days.
Title
MD Part: Trough Levels of BI 754132 Before Third Administration (Cmin,2)
Description
Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,2 (trough levels of BI 754132 before third administration). Multiple dose (MD) part.
Time Frame
Up to 57 days.
Title
MD Part: Plasma Concentration of BI 754132 4, 8 and 14 Weeks After the Third Administration
Description
Plasma concentration of BI 754132 4, 8 and 14 weeks after the third administration. Multiple dose (MD) part.
Time Frame
At Day 85, 113 and Day 155.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Retina-Vitreous Associates Medical Group
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Retina Specialty Institute
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32503
Country
United States
Facility Name
Center for Retina and Macular Disease
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Southeast Retina Center, PC
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
Western Carolina Retinal Associate PA
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
Mid Atlantic Retina
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Retina Consultants of Texas
City
Bellaire
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
Facility Name
Retina Foundation of the Southwest
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Bristol Eye Hospital
City
Bristol
ZIP/Postal Code
BS1 2LX
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L69 3GA
Country
United Kingdom
Facility Name
Moorfields Eye Hospital
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
Links:
URL
https://www.mystudywindow.com
Description
Related Info
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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
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