Diabetic Macular Edema, Diabetic Retinopathy
Conditions
Brief summary
A Phase 2 study to determine the safety and preliminary efficacy of intravitreal injections of AVD-104, a novel glyco-mimetic nanoparticle, in reducing macular edema associated with diabetic retinopathy.
Detailed description
The primary objective is to evaluate the tolerability and treatment effect of intravitreal injections (IVT) of AVD-104 in participants with diabetic macular edema (DME). Participants will receive either three intravitreal injections of low-dose AVD-104 (1.0 mg) each 28 days apart or two intravitreal injections of AVD-104 at a high-dose (2.0 mg) 56 days apart. Serial optical coherence tomography (OCT), ultra wide-field fluorescein angiography, and OCT-angiography (OCT-A) will be performed to evaluate the treatment effect on central subfield thickness (CST) and areas of non-perfusion. All participants will be followed-up for safety until day 84. There will be a planned enrollment up to 30 participants.
Interventions
DRUGAVD-104
An intravitreal injection of 50 microliters at the doses described will be given. Visual acuity, optical coherence tomography thickness and vascular perfusion will be evaluated for an effect of the drug.
Sponsors
Aviceda Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of diabetes mellitus (type 1 or 2), as defined by the World Health Organization and/or American Diabetes Association * Decreased visual acuity (VA) due to DME, with Best corrected visual acuity (BCVA) letter score of 75-20 letters on ETDRS-like charts (20/32-20/320 Snellen equivalent) * DME represented by macular thickening on Spectral domain optical coherence tomography (SD-OCT) involving the center of the macula: Central subfield thickness (CST) ≥325 μm
Exclusion criteria
* Any IVT anti-vascular endothelial growth factor (VEGF) treatment within 3 months before randomization * Any history of pan-retinal photocoagulation (PRP) treatment * Any use of Iluvien® (Alimera Sciences, Inc., Alpharetta, GA) in the last 3 years; or Ozurdex® (Abbvie, Chicago, IL) or Xipere (Bausch & Lomb, Vaughan, Ontario, Canada) in the last 6 months * History of macular laser photocoagulation * Any signs of high-risk proliferative diabetic retinopathy (PDR)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious Adverse Events | 3 months | Number of participants with any evidence of serious adverse events as assessed by ocular examination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Effect | 3 months | Evaluate the treatment effect of AVD-104 at multiple doses on central subfield thickness (CST) as measured by Spectral-domain optical coherence tomography (SD-OCT) |
| Treatment Effect - Vision | 3 months | Evaluate the treatment effect of AVD-104 at multiple doses on Best-corrected visual acuity (BCVA) using ETDRS ((Early-Treatment Diabetic Retinopathy Study) visual acuity charts |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose AVD-104 Three intravitreal injections at 1.0 milligram per eye each 28 days apart will be administered to the study eye. Participants will be followed for 84 days total.
AVD-104: An intravitreal injection of 50 microliters at the doses described will be given. Visual acuity, optical coherence tomography thickness and vascular perfusion will be evaluated for an effect of the drug. | 10 |
| High Dose AVD-104 Two intravitreal injections at 2.0 milligrams per eye 56 days apart will be administered to the study eye. Participants will be followed for 84 days total.
AVD-104: An intravitreal injection of 50 microliters at the doses described will be given. Visual acuity, optical coherence tomography thickness and vascular perfusion will be evaluated for an effect of the drug. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by sponsor | 7 | 9 |
Baseline characteristics
| Characteristic | Low Dose AVD-104 | High Dose AVD-104 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 65.2 years STANDARD_DEVIATION 6.44 | 66.6 years STANDARD_DEVIATION 11.14 | 66.0 years STANDARD_DEVIATION 9.01 |
| Race/Ethnicity, Customized Ethnicity American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity White | 7 Participants | 11 Participants | 18 Participants |
| Region of Enrollment United States | 10 participants | 11 participants | 21 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 5 / 10 | 0 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Incidence of Serious Adverse Events
Number of participants with any evidence of serious adverse events as assessed by ocular examination
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose AVD-104 | Incidence of Serious Adverse Events | 0 Participants |
| High Dose AVD-104 | Incidence of Serious Adverse Events | 0 Participants |
Secondary
Treatment Effect
Evaluate the treatment effect of AVD-104 at multiple doses on central subfield thickness (CST) as measured by Spectral-domain optical coherence tomography (SD-OCT)
Time frame: 3 months
Population: The trial was discontinued due to Intellectual property (IP) supply issues and study funding constraints. Only 6 participants received treatment with scheduled follow-up to 3 months and gradable SD-OCT. The planned treatment schedule for 30 participants was not achieved.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose AVD-104 | Treatment Effect | Baseline | 653.5 microns | Standard Deviation 116.7 |
| Low Dose AVD-104 | Treatment Effect | Month 3 | 803.5 microns | Standard Deviation 10.6 |
| High Dose AVD-104 | Treatment Effect | Baseline | 432.0 microns | Standard Deviation 111.8 |
| High Dose AVD-104 | Treatment Effect | Month 3 | 560.3 microns | Standard Deviation 254.1 |
Secondary
Treatment Effect - Vision
Evaluate the treatment effect of AVD-104 at multiple doses on Best-corrected visual acuity (BCVA) using ETDRS ((Early-Treatment Diabetic Retinopathy Study) visual acuity charts
Time frame: 3 months
Population: The trial was discontinued due to IP supply issues and study funding constraints. Only 6 participants received treatment up to 3 months of the planned 30 participants. 10 of the participants only received a single injection. This is a limited sample and the planned treatment schedule was not achieved.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose AVD-104 | Treatment Effect - Vision | Baseline | 52 ETDRS letters | Standard Deviation 11.3 |
| Low Dose AVD-104 | Treatment Effect - Vision | Month 3 | 25.5 ETDRS letters | Standard Deviation 0.7 |
| High Dose AVD-104 | Treatment Effect - Vision | Baseline | 67 ETDRS letters | Standard Deviation 9.8 |
| High Dose AVD-104 | Treatment Effect - Vision | Month 3 | 68 ETDRS letters | Standard Deviation 16.3 |