Diabetic Macular Edema
Conditions
Keywords
Allegenesis, Diabetic Macular Edema, AG-73305
Brief summary
This is a multi-centered, open-labeled, single ascending-dose-cohort study to evaluate the safety and efficacy of 4 dose cohorts of AG-73305 administered by intravitreal injection in patients with diabetic macular edema (DME). The objectives of this study were to evaluate the safety, tolerability, duration of effect, systemic pharmacokinetic and immunogenicity profiles of ascending doses of AG-73305 administered by intravitreal injection to patients with DME. Pharmacodynamic endpoints (e.g., best-corrected visual acuity \[BCVA\], spectral domain optical coherence tomography \[SD-OCT\], and optical coherence tomography angiography \[OCT-A\]) were evaluated over 6 months post-treatment. The maximum tolerated dose or the highest administered dose was evaluated for future studies.
Interventions
BIOLOGICALAG-73305
drug product solution
Sponsors
Lexitas Pharma Services, Inc.
Allgenesis Biotherapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years of age or older at the screening visit 2. Prior diagnosis of diabetes mellitus (Type 1 or Type 2) as defined by World Health Organization or American Diabetes Association 3. Presence of center-involving DME in the study eye with CST ≥ 325 μm 4. Visual acuity loss in the study eye attributed to DME with screening and baseline ETDRS BCVA letter score of 20 to 55 (20/400 to 20/80 Snellen equivalent) in the sentinel patients and 35 to 70 (20/200 to 20/40 Snellen equivalent) in the non-sentinel patients 5. Cohort 1: Previously treated with an anti-VEGF in the study eye; Cohorts 2, 3, and 4: Previously treated or treatment-naïve to the study eye
Exclusion criteria
1. Uncontrolled diabetes mellitus, defined as hemoglobin A1c \> 12.0% at Screening 2. Uncontrolled hypertension with systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100 mmHg at Screening or Baseline 3. Chronic renal disease 4. Any active infection in either eye 5. Any anti-vascular endothelial growth factor (VEGF) treatment in the study eye within 6 to 8 weeks prior to Baseline 6. Use of Ozurdex (dexamethasone) within 6 months prior to Baseline or any use of Iluvien (fluocinolone acetonide) in the study eye 7. Uncontrolled intraocular pressure (IOP), defined as an IOP \> 25 mmHg, despite anti-glaucoma medications in the study eye at the time of screening or controlled glaucoma that requires management with \> 2 topical hypotensive medications 8. Any anti-integrin therapy (e.g., Xiidra) within 60 days before baseline in the study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 1 month after dosing | BCVA assessments were performed at all visits utilizing ETDRS charts to assess changes in vision over time. The charts were designed for use at 4 meters. BCVA assessments were performed by certified technicians to minimize bias. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Central Subfield Thickness (CST) | 1 month after dosing | SD-OCT imaging was performed at all visits utilizing Heidelberg Spectralis imaging equipment to assess changes over time in the structural details of the posterior segment of the eye. All images were graded by a central reading center. |
Countries
United States
Participant flow
Recruitment details
Patients were screened based on the inclusion/exclusion criteria at 6 clinical sites in the US between May 2022 to December 2023.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 A single intravitreal (IVT) dose of 0.5 mg AG-73305
AG-73305: AG-73305 Ophthalmic Solution | 3 |
| Cohort 2 A single IVT dose of 1 mg AG-73305
AG-73305: AG-73305 Ophthalmic Solution | 6 |
| Cohort 3 A single IVT dose of 2 mg AG-73305
AG-73305: AG-73305 Ophthalmic Solution | 8 |
| Cohort 4 A single IVT dose of 4 mg AG-73305
AG-73305: AG-73305 Ophthalmic Solution | 8 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 1 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 7 Participants | 0 Participants | 15 Participants |
| Age, Continuous | 64.2 years STANDARD_DEVIATION 9.9 | 59.6 years STANDARD_DEVIATION 11.2 | 54.5 years STANDARD_DEVIATION 14.7 | 70 years STANDARD_DEVIATION 3.6 | 60.3 years STANDARD_DEVIATION 12.2 |
| Best-corrected Visual Acuity | 48.7 ETDRS letters STANDARD_DEVIATION 11.9 | 62.4 ETDRS letters STANDARD_DEVIATION 5.4 | 63.0 ETDRS letters STANDARD_DEVIATION 3.2 | 56.7 ETDRS letters STANDARD_DEVIATION 1.5 | 58.6 ETDRS letters STANDARD_DEVIATION 8.8 |
| Central Subfield Thickness | 657.732 micrometers STANDARD_DEVIATION 169.99 | 444.818 micrometers STANDARD_DEVIATION 163.635 | 464.488 micrometers STANDARD_DEVIATION 140.934 | 522.017 micrometers STANDARD_DEVIATION 197.845 | 511.475 micrometers STANDARD_DEVIATION 174.539 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 5 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 7 Participants | 3 Participants | 24 Participants |
| Region of Enrollment United States | 6 participants | 8 participants | 8 participants | 3 participants | 25 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 3 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 3 | 4 / 6 | 6 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 1 / 8 | 1 / 8 |
Outcome results
Primary
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA)
BCVA assessments were performed at all visits utilizing ETDRS charts to assess changes in vision over time. The charts were designed for use at 4 meters. BCVA assessments were performed by certified technicians to minimize bias.
Time frame: 1 month after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 3.7 ETDRS letters | Standard Deviation 1.2 |
| Cohort 2 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 9.2 ETDRS letters | Standard Deviation 5.3 |
| Cohort 3 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 4.3 ETDRS letters | Standard Deviation 3.9 |
| Cohort 4 | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) | 7.7 ETDRS letters | Standard Deviation 7.7 |
Secondary
Mean Change From Baseline in Central Subfield Thickness (CST)
SD-OCT imaging was performed at all visits utilizing Heidelberg Spectralis imaging equipment to assess changes over time in the structural details of the posterior segment of the eye. All images were graded by a central reading center.
Time frame: 1 month after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Change From Baseline in Central Subfield Thickness (CST) | 2.287 μm | Standard Deviation 9.819 |
| Cohort 2 | Mean Change From Baseline in Central Subfield Thickness (CST) | -263.167 μm | Standard Deviation 221.986 |
| Cohort 3 | Mean Change From Baseline in Central Subfield Thickness (CST) | -70.443 μm | Standard Deviation 175.147 |
| Cohort 4 | Mean Change From Baseline in Central Subfield Thickness (CST) | -50.571 μm | Standard Deviation 108.694 |