A Study of NGM621 in Participants With Geographic Atrophy

A Phase 2 Multicenter, Randomized, Double-Masked, Sham-Controlled Study of the Safety and Efficacy of Intravitreal Injections of NGM621 in Subjects With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04465955

Acronym

CATALINA

Enrollment

320

Registered

2020-07-10

Start date

2020-07-22

Completion date

2022-08-16

Last updated

2025-07-01

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

Conditions

Geographic Atrophy

Brief summary

This is a multi-center evaluation of NGM621 in a randomized, double-masked, sham-controlled study in participants with Geographic Atrophy secondary to Age-related Macular Degeneration.

Interventions

BIOLOGICALNGM621

NGM621 Dose 1

OTHERSham Comparator

Sham Comparator

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

55 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female (non-pregnant, non-lactating) subjects ≥ 55 years * Standard luminance BCVA score of 34 letters or better using ETDRS charts at the starting distance of 4 meters (approximately 20/200 Snellen equivalent or better) in study eye * Clinical diagnosis of GA secondary to AMD: 1. Total GA area must be ≥ 2.5 and ≤ 17.5 mm² 2. If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm² (0.5 DA), with the overall area of GA ≥ 2.5 and ≤ 17.5 mm² 3. Well demarcated GA with no anatomical evidence of current or prior CNV in the study eye

Exclusion criteria

Study Eye * GA secondary to a condition other than AMD in either eye (e.g., monogenetic macular dystrophies like Stargardt disease, cone rod dystrophy, or toxic maculopathies) * Any history of or active choroidal neovascularization (CNV) Both Eyes * Any history of or active bacterial, viral, fungal, or parasitic infection in either eye in the 3 months prior to randomization

Design outcomes

Primary

Measure	Time frame	Description
The Rate of Change From Baseline in Geographic Atrophy (GA) Lesion Area	Baseline to Week 52	The rate of change from baseline in GA lesion area was measured by a non-invasive imaging technique called fundus autofluorescence (FAF) over the 52 weeks of treatment. FAF refers to the spontaneous emission of light by certain substances within the eye when exposed to a specific wavelength of light and involves quantifying the area and progression of atrophic lesions. The minimal GA lesion area is zero, the maximal GA lesion area is unknown. The higher the GA lesion area, the worse the visual outcome.
Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Baseline to end of study (Week 56)	A treatment-emergent adverse event (TEAE) was an adverse event (AE) that occurred during or after the first dose of study treatment.

Secondary

Measure	Time frame	Description
The Change From Baseline in Best Corrected Visual Acuity Score	Baseline up to Week 52	Best Corrected Visual Acuity Score is the best possible vision an eye can achieve with corrective lenses, typically glasses or contact lenses. BCVA was assessed by the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. ETDRS letter score is calculated when \>20 letters are read correctly at 4.0 meters; the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters plus 30. If \<20 letters are read correctly at 4.0 meters, the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters (number of letters recorded on line 1.0), plus the total number of letters in the first six lines read correctly at 1.0 meter. Therefore, the ETDRS letter score could result in a score of 0-100, where lower scores indicate better vision. The change from baseline in BCVA is being report with negative scores indicating an improvement in vision.
The Change From Baseline in Systemic Complement Activity (CH50)	Baseline up to Week 52	Systemic Complement Activity is a blood test that measures the overall activity of the complement system, a group of proteins crucial for the immune system's function. Low CH50 levels can be associated with certain infections. CH50 levels of 41 to 90 hemolytic units per mL (U/mL) is considered normal. The change from baseline in CH50 is being reported.
Number of Anti-Drug Antibody (ADA)-Negative Participants	Baseline up to Week 52	The incidence of anti-drug antibody (ADA) was assessed in serum.
The Change From Baseline in Low Luminance Visual Acuity Score	Baseline up to Week 52	Low Luminance Visual Acuity Score measures vision in low-light conditions. It was assessed by the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. ETDRS letter score is calculated when \>20 letters are read correctly at 4.0 meters; the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters plus 30. If \<20 letters are read correctly at 4.0 meters, the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters (number of letters recorded on line 1.0), plus the total number of letters in the first six lines read correctly at 1.0 meter. Therefore, the ETDRS letter score could result in a score of 0-100, where lower scores indicate better vision. A lower (negative) LLVA score compared to baseline indicates a decline in visual acuity. A higher (positive) LLVA score compared to baseline indicates an improvement in visual acuity.
The Change From Baseline in Low Luminance Deficit Score	Baseline up to Week 52	Low Luminance Deficit (LLD) Score was assessed by the Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at a starting distance of 4 meters. ETDRS letter score is calculated when \>20 letters are read correctly at 4.0 meters; the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters plus 30. If \<20 letters are read correctly at 4.0 meters, the visual acuity letter score is equal to the total number of letters read correctly at 4.0 meters (number of letters recorded on line 1.0), plus the total number of letters in the first six lines read correctly at 1.0 meter. Therefore, the ETDRS letter score could result in a score of 0-100, where lower scores indicate better vision. A LLD is the difference between standard visual acuity and LLVA, with a LLD \>13 ETDRS letters suggesting potential visual abnormality. The change from baseline in LLD is being report with negative scores indicating an improvement in vision.
The Change From Baseline in Geographic Atrophy (GA) Lesion Area	Baseline up to Week 52	Geographic atrophy lesion area was measured by a non-invasive imaging technique called fundus autofluorescence (FAF). FAF refers to the spontaneous emission of light by certain substances within the eye when exposed to a specific wavelength of light and involves quantifying the area and progression of atrophic lesions. The minimal GA lesion area is zero, the maximal GA lesion area is unknown. The higher the GA lesion area, the worse the visual outcome.
The Change From Baseline in Binocular Critical Print Size	Baseline up to Week 52	Binocular critical print size was assessed by the Minnesota Low-Vision Reading Test (MNRead) or Radner reading charts. MNRead uses a logarithmic scale (LogMAR) to represent print sizes, with each step representing a 0.1 LogMAR difference. The chart ranges from +1.3 LogMAR (equivalent to 20/400 at 40 cm) to -0.5 LogMAR (equivalent to 20/6 at 40 cm). The change from baseline in binocular critical print size is being reported with a higher (positive) LogMAR value for critical print size indicating that a person needs larger print sizes to maintain their maximum reading speed, while a lower (negative) LogMAR value indicates that they can read smaller print sizes at their maximum speed.
The Change From Baseline in Binocular Reading Acuity	Baseline up to Week 52	Binocular reading acuity was assessed by the Minnesota Low-Vision Reading Test (MNRead) or Radner reading charts. MNRead uses a logarithmic scale (LogMAR) to represent print sizes, with each step representing a 0.1 LogMAR difference. The chart ranges from +1.3 LogMAR (equivalent to 20/400 at 40 cm) to -0.5 LogMAR (equivalent to 20/6 at 40 cm). Binocular reading acuity is the smallest print size (in LogMAR) that a person can read easily and accurately. The change from baseline in binocular reading acuity is being reported with a higher LogMAR value for reading acuity indicates poorer reading ability, while a lower LogMAR value indicates better reading ability.
The Change From Baseline in Functional Reading Independence Index Composite Score	Baseline up to Week 52	The Functional Reading Independence (FRI) Index Composite Score is a 7-item patient questionnaire developed to evaluate the effect of geography atrophy on a patient's ability to independently perform reading activities. The FRI Index yields mean scores ranging from 1-4, with 1=unable to do and 4=totally independent. The FRI Index composite score is calculated by averaging the item-level scores across the seven questions, higher sores indicate better FRI. The change from baseline in FRI is being reported with lower (negative) values indicating a decline in FRI.
The Change From Baseline in National Eye Institute Visual Functioning Questionnaire Composite Score	Baseline up to Week 52	The National Eye Institute Visual Functioning Questionnaire Composite Score is calculated by averaging the scores of the 11 vision-targeted subscales, excluding the general health rating question, on a scale of 0 to 100, with higher scores indicating better vision-related function. The change from baseline is being reported with a negative value indicating a decline in vision function.
The Change From Baseline in Average Binocular Reading Speed	Baseline up to Week 52	Average binocular reading speed was assessed by Minnesota Low-Vision Reading Test (MNRead) or Radner reading charts. The change from baseline in average binocular reading speed is reported with a higher (positive) reading speed (wpm) indicates better reading ability, while a lower (negative) reading speed indicates poorer reading ability.
The Rate of Change From Baseline in the Square Root of Geographic Atropy (GA) Lesion Area	Baseline up to Week 52	Geographic atrophy lesion area was measured by fundus autofluorescence (FAF). FAF refers to the spontaneous emission of light by certain substances within the eye when exposed to a specific wavelength of light and involves quantifying the area and progression of atrophic lesions.

Countries

United States

Participant flow

Recruitment details

A total of 320 participants who met all inclusion criteria and no exclusion criteria were randomized to 1 of 4 treatment groups (NGM621 treatment or sham comparator administered either every 4 weeks or every 8 weeks) at 65 sites in the United States. Participants were randomized to 1 of the 4 treatment groups in a ratio of 2 (NGM621 Q4W):1 (Placebo Q4W):2 (NGM621 Q8W):1 (Placebo Q8W).

Participants by arm

Arm	Count
NGM621 Q4W Participants who were randomized to a single intravitreal (IVT) injection of 15 mg of NGM621 every 4 weeks (Q4W).	108
NGM621 Q8W Participants who were randomized to a single intravitreal (IVT) injection of 15 mg of NGM621 every 8 weeks (Q8W).	104
Sham Q4W+Q8W Participants who were either randomized to a single intravitreal (IVT) injection of sham comparator every 4 weeks (Q4W) or every 8 weeks (Q8W). As prespecified in the protocol, the sham comparator groups were pooled for analysis purposes.	106
Total	318

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	6	5	1
Overall Study	Lost to Follow-up	2	0	3
Overall Study	Other	1	1	3
Overall Study	Withdrew consent	6	10	7

Baseline characteristics

Characteristic	NGM621 Q4W	NGM621 Q8W	Sham Q4W+Q8W	Total
Age, Continuous	78.5 years STANDARD_DEVIATION 8.17	79.1 years STANDARD_DEVIATION 7.51	77.6 years STANDARD_DEVIATION 8.42	78.4 years STANDARD_DEVIATION 8.04
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Asian	0 Participants	1 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Multiple	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized White	107 Participants	102 Participants	101 Participants	310 Participants
Region of Enrollment United States	108 participants	104 participants	106 participants	318 participants
Sex: Female, Male Female	67 Participants	63 Participants	68 Participants	198 Participants
Sex: Female, Male Male	41 Participants	41 Participants	38 Participants	120 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	4 / 108	2 / 104	2 / 106
other Total, other adverse events	33 / 108	34 / 104	31 / 106
serious Total, serious adverse events	32 / 108	24 / 104	29 / 106

Outcome results

Primary

Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye

A treatment-emergent adverse event (TEAE) was an adverse event (AE) that occurred during or after the first dose of study treatment.

Time frame: Baseline to end of study (Week 56)

Population: TEAEs were assessed in the Safety Analysis Set.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE	57 Participants
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Treatment-related TEAE	6 Participants
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Serious TEAE	8 Participants
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE Leading to Treatment Discontinuation	0 Participants
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Sight Threatening TEAE	6 Participants
NGM621 Q4W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Severe TEAE	1 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Severe TEAE	3 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE	51 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE Leading to Treatment Discontinuation	1 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Sight Threatening TEAE	6 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Treatment-related TEAE	5 Participants
NGM621 Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Serious TEAE	8 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Treatment-related TEAE	1 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Serious TEAE	3 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Severe TEAE	0 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE Leading to Treatment Discontinuation	0 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any TEAE	49 Participants
Sham Q4W+Q8W	Number of Participants With Ocular Treatment-emergent Adverse Events in the Study Eye	Any Sight Threatening TEAE	3 Participants

Primary

The Rate of Change From Baseline in Geographic Atrophy (GA) Lesion Area

The rate of change from baseline in GA lesion area was measured by a non-invasive imaging technique called fundus autofluorescence (FAF) over the 52 weeks of treatment. FAF refers to the spontaneous emission of light by certain substances within the eye when exposed to a specific wavelength of light and involves quantifying the area and progression of atrophic lesions. The minimal GA lesion area is zero, the maximal GA lesion area is unknown. The higher the GA lesion area, the worse the visual outcome.

Time frame: Baseline to Week 52

Population: The rate of change from baseline in the GA lesion area was assessed in the modified Intent-to-Treat population.

Arm	Measure	Value (MEAN)	Dispersion
NGM621 Q4W	The Rate of Change From Baseline in Geographic Atrophy (GA) Lesion Area	2.243 mm^2 per year	Standard Error 0.138
NGM621 Q8W	The Rate of Change From Baseline in Geographic Atrophy (GA) Lesion Area	2.237 mm^2 per year	Standard Error 0.14
Sham Q4W+Q8W	The Rate of Change From Baseline in Geographic Atrophy (GA) Lesion Area	2.393 mm^2 per year	Standard Error 0.138

Comparison: Rate of Change Difference Between NGM621 Q4W and Pooled Shamp-value: 0.434595% CI: [-0.528, 0.227]Random coefficient model

Comparison: Rate of Change Difference Between NGM621 Q8W and Pooled Shamp-value: 0.421795% CI: [-0.536, 0.225]Random coefficient model

Secondary