A Study Assessing the Safety, Tolerability, and Efficacy of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)

A Phase II, Multicenter, Randomized, Single-Masked, Sham-Controlled Study to Assess Safety, Tolerability, and Efficacy of Intravitreal Injections of FHTR2163 in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration (GALLEGO)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03972709

Acronym

GALLEGO

Enrollment

372

Registered

2019-06-04

Start date

2019-06-03

Completion date

2022-10-27

Last updated

2024-03-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Geographic Atrophy, Macular Degeneration, Age-Related

Brief summary

This study will evaluate the safety, tolerability, and efficacy of intravitreal injections of galegenimab (FHTR2163) administered every 4 weeks (Q4W) or every 8 weeks (Q8W) for approximately 76 weeks in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) compared with sham control. After completing the study's last visit (Week 76), eligible participants will have the option to enroll in open-label extension study NCT04607148 (GR42558) and receive open-label galegenimab (FHTR2163) injections.

Interventions

DRUGSham Control

Sham control

DRUGGalegenimab

Intravitreal (ITV) injections of galegenimab

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age \>/= 60 years at time of signing Informed Consent Form; * Visual acuity: best-corrected visual acuity (BCVA) letter score \>/= 24 letters (Snellen equivalent of 20/320 or better). If the study eye BCVA letter score is \>/= 69 letters (Snellen equivalent of 20/40 or better), the non-study eye must have a BCVA letter score of \>/= 44 letters (Snellen equivalent of 20/125 or better); * Well-demarcated area of GA secondary to AMD with no evidence of prior or active choroidal neovascularization (CNV) in either eye.

Exclusion criteria

Ocular

Design outcomes

Primary

Measure	Time frame	Description
Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 72 as Measured by Fundus Autofluorescence (FAF)	Baseline, Week 72	GA is an advanced stage of age-related macular degeneration (AMD) and is characterized by loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. In the early stages of GA, patients typically show minimal changes in central visual acuity although patients often still experience significant symptoms from visual dysfunction, such as reduced contrast sensitivity, and a decrease in reading speed. In the later stages, as the GA lesion expands into the fovea, a profound decrease in central visual acuity occurs with a decline in activities of daily living. The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).

Secondary

Measure	Time frame	Description
Percentage of Participants With Ocular Adverse Events in the Fellow Eye	From baseline to Week 76	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Ocular AEs are the events which are localized in the ocular region.
Percentage of Participants With Systemic Adverse Events	From baseline to Week 76	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Non-ocular AEs were the systemic events.
Percentage of Participants With Serious Adverse Events (SAEs)	From baseline to Week 76	SAEs are defined as fatal, life threatening, requires or prolongs patient hospitalization, results in persistent or significant disability/incapacity, or is a significant medical event in the investigator's judgement.
Percentage of Participants With Ocular Adverse Events in the Study Eye	From baseline to Week 76	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Ocular AEs are the events which are localized in the ocular region.
Percentage of Participants With Adverse Events Leading to Study Discontinuation	From baseline to Week 76	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Non-ocular AEs were the systemic events.
Mean Change in Best Corrected Visual Acuity (BCVA) Score From Baseline to Week 72 as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Under Low-luminance Conditions	Baseline, Week 72	BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m) under low-luminance conditions. A decrease in the VA score indicates a worsening in visual acuity. BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity.
Mean Change in BCVA Score From Baseline to Week 72 as Assessed by ETDRS Chart	Baseline, Week 72	BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m). A decrease in the VA score indicates a worsening in visual acuity. BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity.
Percentage of Participants With Adverse Events of Special Interest (AESIs)	From baseline to Week 76	AESIs include 1.) cases of potential drug-induced liver injury that include an elevated alanine transaminase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law 2.) Suspected transmission of an infectious agent by galegenimab 3.) AEs resulting from medication error 4.) Sight-threatening AEs of the following criteria: It causes a decrease of \>= 30 letters in visual acuity (VA) score, compared with the most recent prior VA assessment, that lasts more than 1 hour and is attributable to galegenimab; it requires surgical intervention to prevent permanent loss of sight; associated with severe (Grade 4+) intraocular inflammation (IOI) and/or IOI-associated retinal vasculitis; in the opinion of the investigator, it may require medical intervention to prevent permanent loss of sight.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Galegenimab Q4W Participants will receive galegenimab every 4 weeks (Q4W). After completing the study's last visit (Week 76), eligible participants will have the option to enroll in open-label extension study NCT04607148 (GR42558) and receive open-label galegenimab injections.	149
Galegenimab Q8W Participants will receive galegenimab every 8 weeks (Q8W). After completing the study's last visit (Week 76), eligible participants will have the option to enroll in open-label extension study NCT04607148 (GR42558) and receive open-label galegenimab injections.	75
All Sham Participants will receive Sham-control Q4W or Q8W. After completing the study's last visit (Week 76), eligible participants will have the option to enroll in open-label extension study NCT04607148 (GR42558) and receive open-label galegenimab injections.	148
Total	372

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	3	1	4
Overall Study	COVID-19	0	1	1
Overall Study	Death	5	1	4
Overall Study	Lost to Follow-up	6	1	2
Overall Study	Missed Study Visits	1	0	0
Overall Study	Physician Decision	1	0	0
Overall Study	Study Terminated by Sponsor	48	25	50
Overall Study	Subject Discontinuation Due to AEs with Onset Beyond Study Reporting Period	0	1	0
Overall Study	Subject Expired Due to SAE with Onset Beyond Protocol Reporting Period	0	1	0
Overall Study	Subject in Nursing Home, Unable to Attend Visit	0	0	1
Overall Study	Subject Moved	0	1	0
Overall Study	Subject Unable to be Contacted	0	1	0
Overall Study	Withdrawal by Subject	18	7	14

Baseline characteristics

Characteristic	Galegenimab Q4W	Galegenimab Q8W	All Sham	Total
Age, Continuous	78.9 Years STANDARD_DEVIATION 7.3	78.4 Years STANDARD_DEVIATION 7.8	78.0 Years STANDARD_DEVIATION 7.7	78.4 Years STANDARD_DEVIATION 7.5
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	4 Participants	3 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	143 Participants	71 Participants	145 Participants	359 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants	0 Participants	0 Participants	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	1 Participants	3 Participants
Race (NIH/OMB) White	147 Participants	74 Participants	146 Participants	367 Participants
Sex: Female, Male Female	89 Participants	50 Participants	83 Participants	222 Participants
Sex: Female, Male Male	60 Participants	25 Participants	65 Participants	150 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	5 / 149	1 / 75	4 / 148
other Total, other adverse events	53 / 149	21 / 75	38 / 148
serious Total, serious adverse events	29 / 149	16 / 75	34 / 148

Outcome results

Primary

Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 72 as Measured by Fundus Autofluorescence (FAF)

GA is an advanced stage of age-related macular degeneration (AMD) and is characterized by loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. In the early stages of GA, patients typically show minimal changes in central visual acuity although patients often still experience significant symptoms from visual dysfunction, such as reduced contrast sensitivity, and a decrease in reading speed. In the later stages, as the GA lesion expands into the fovea, a profound decrease in central visual acuity occurs with a decline in activities of daily living. The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).

Time frame: Baseline, Week 72

Population: Modified intent-to-treat (mITT) population includes all randomized patients who received at least one dose of study drug, and have a baseline measurement and at least one post-baseline measurement of GA area by FAF, subjects grouped according to treatment assigned at randomization. Participants analyzed in this outcome measure were those included in mixed models for repeated measures (MMRM) analysis.

Arm	Measure	Value (MEAN)	Dispersion
Galegenimab Q4W	Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 72 as Measured by Fundus Autofluorescence (FAF)	2.60 mm^2	Standard Error 0.133
Galegenimab Q8W	Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 72 as Measured by Fundus Autofluorescence (FAF)	2.43 mm^2	Standard Error 0.189
All Sham	Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 72 as Measured by Fundus Autofluorescence (FAF)	2.31 mm^2	Standard Error 0.133

p-value: 0.120695% CI: [-0.08, 0.66]MMRM

p-value: 0.612795% CI: [-0.34, 0.57]MMRM

Secondary

Mean Change in BCVA Score From Baseline to Week 72 as Assessed by ETDRS Chart

BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m). A decrease in the VA score indicates a worsening in visual acuity. BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity.

Time frame: Baseline, Week 72

Population: mITT population includes all randomized patients who received at least one dose of study drug, and have a baseline measurement and at least one post-baseline measurement of GA area by FAF, subjects grouped according to treatment assigned at randomization. Participants analyzed in this outcome measure were those included in mixed models for repeated measures (MMRM) analysis.

Arm	Measure	Value (MEAN)	Dispersion
Galegenimab Q4W	Mean Change in BCVA Score From Baseline to Week 72 as Assessed by ETDRS Chart	-5.05 ETDRS letter	Standard Error 1.444
Galegenimab Q8W	Mean Change in BCVA Score From Baseline to Week 72 as Assessed by ETDRS Chart	-5.68 ETDRS letter	Standard Error 2.032
All Sham	Mean Change in BCVA Score From Baseline to Week 72 as Assessed by ETDRS Chart	-5.88 ETDRS letter	Standard Error 1.456

p-value: 0.686595% CI: [-3.22, 4.88]MMRM

p-value: 0.935595% CI: [-4.73, 5.13]MMRM

Secondary

Mean Change in Best Corrected Visual Acuity (BCVA) Score From Baseline to Week 72 as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Under Low-luminance Conditions

BCVA score was based on the number of letters read correctly on the ETDRS visual acuity chart assessed at a starting distance of 4 meters (m) under low-luminance conditions. A decrease in the VA score indicates a worsening in visual acuity. BCVA score testing was performed prior to dilating the eyes. BCVA score ranges from 0 to 100 letters in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A negative change from baseline indicates a decrease in the visual acuity.

Time frame: Baseline, Week 72

Arm	Measure	Value (MEAN)	Dispersion
Galegenimab Q4W	Mean Change in Best Corrected Visual Acuity (BCVA) Score From Baseline to Week 72 as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Under Low-luminance Conditions	-3.45 ETDRS letters	Standard Error 1.344
Galegenimab Q8W	Mean Change in Best Corrected Visual Acuity (BCVA) Score From Baseline to Week 72 as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Under Low-luminance Conditions	-3.54 ETDRS letters	Standard Error 1.974
All Sham	Mean Change in Best Corrected Visual Acuity (BCVA) Score From Baseline to Week 72 as Assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) Chart Under Low-luminance Conditions	-3.06 ETDRS letters	Standard Error 1.339

p-value: 0.838895% CI: [-4.14, 3.36]MMRM

p-value: 0.841295% CI: [-5.18, 4.23]MMRM

Secondary

Percentage of Participants With Adverse Events Leading to Study Discontinuation

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Non-ocular AEs were the systemic events.