DAVIO

29 evidence topics · 4 sources

Objective

Primary and secondary objectives

“The primary objective of this study was to evaluate the safety and determine the maximum tolerated dose of the EYP-1901 intravitreal insert for the treatment of patients with wAMD, based on ocular treatment-emergent adverse events (TEAEs) in the study and fellow eye, as well as nonocular adverse events (AEs), including clinical laboratory findings.” (opens the source at this quote in a new tab)
“Posthoc exploratory analyses were conducted to evaluate reduction in treatment burden and supplemental injection-free rate.” (opens the source at this quote in a new tab)

Location and study date

Sites and study period

“The study was a phase I, multicenter (11 sites in the US), prospective, open-label, dose escalation trial.” (opens the source at this quote in a new tab)
“The study was conducted from January 2021 to May 2022.” (opens the source at this quote in a new tab)

Registry dates

Field	Quoted record
Study start (actual)	“2021-01-20”
Primary completion (actual)	“2022-05-11”

Study design

Dose-escalation design

“All patients in the study received EYP-1901, and both patients and investigators were not masked.” (opens the source at this quote in a new tab)
“According to the study protocol, 3 successive dose cohorts were planned to be enrolled in the dose-escalation phase, and depending on toxicity, up to 26 patients could have been enrolled during this phase.” (opens the source at this quote in a new tab)
“The study duration was 48 weeks, and the study consisted of a patient screening phase and a sequential dose-escalation phase.” (opens the source at this quote in a new tab)

Criteria for additional anti-VEGF injections

“Administration of additional Food and Drug Administration-approved anti-VEGF treatment for wAMD (e.g., ranibizumab or aflibercept; not brolucizumab) or off-label bevacizumab was allowed at the investigator's discretion if a patient had a new or worsening vision-threatening hemorrhage since day 0 due to wAMD, an increase in CST of >75 μm from day 0, or a loss of ≥10 ETDRS letters from day 0 with intraretinal or subretinal fluid and/or hemorrhage judged to be the cause of BCVA loss.” (opens the source at this quote in a new tab)

Eligibility criteria

Key inclusion criteria

“They must have received ≥3 prior injections with the same anti-VEGF agent (including bevacizumab, ranibizumab, or aflibercept) in the 6 months prior to the screening visit, in the study eye.” (opens the source at this quote in a new tab)
“Patients must have had best-corrected visual acuity (BCVA), using ETDRS charts, of 25 letters (Snellen equivalent, 20/320) to 85 letters (Snellen equivalent, 20/20).” (opens the source at this quote in a new tab)
“Notably, patients were not excluded based on fluid levels or CST-based criteria.” (opens the source at this quote in a new tab)

Treatment

Single intravitreal administration after standard-of-care anti-VEGF

“Patients received a single intravitreal administration of EYP-1901 in the study eye on day 0 using a preloaded applicator, 7 to 10 days following their last anti-VEGF injection.” (opens the source at this quote in a new tab)

Dose cohorts as treated

“Patients were assigned to 1 of 4 cohorts based on their received dose: 440 μg cohort (1 insert; n = 3), 1030 μg cohort (1 insert; n = 1), 2060 μg cohort (2 inserts; n = 8), 3090 μg cohort (3 inserts; n = 5).” (opens the source at this quote in a new tab)

Injector deviation in the high-dose cohort

“Investigators experienced difficulties with the injector related to the advancement of the plunger as it pushed the 3 inserts (1030 μg each) through the needle.” (opens the source at this quote in a new tab)
“The injector issues that caused the deviation have been resolved in the subsequent phase II DAVIO 2 trial, and the device continues to be in development.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using ocular and nonocular treatment-emergent adverse events as the primary endpoint

Registered primary and secondary outcomes

Role	Quoted record
Primary outcome	“Incidence of ocular (study eye) and systemic treatment emergent adverse events (TEAEs)”
Secondary outcome	“Change in best corrected visual acuity (BCVA) by EDTRS”
Secondary outcome	“Mean change in central subfield thickness (CST)”

Maintenance of BCVA and CST as the targeted efficacy signal

“For this reason, patients who were already stable on anti-VEGF therapy were recruited for the DAVIO Trial. As a result, instead of the rapid improvement seen with typical anti-VEGF clinical trials in a treatment-naive population, the maintenance of stable BCVA and CST was targeted and observed in this study.” (opens the source at this quote in a new tab)

Definition of treatment burden

“Preenrollment and postenrollment treatment burden, defined as the number of injections during the 12-month period before or after the EYP-1901 injection, were derived for each patient.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Sample size

“No formal sample size calculations were performed.” (opens the source at this quote in a new tab)
“All 17 patients were included in the safety analyses.” (opens the source at this quote in a new tab)
“As a result, all secondary and exploratory analyses included only the 16 patients who completed the study.” (opens the source at this quote in a new tab)

Description of analysis sets

Descriptive analyses and exclusion of one participant

“All safety, tolerability, and secondary and exploratory parameters were reported using descriptive summary statistics. No inferential statistical analysis was planned.” (opens the source at this quote in a new tab)
“Because no additional data were collected after week 16, the study sponsor decided to exclude this patient from the secondary and exploratory analyses to avoid the potential to skew the data.” (opens the source at this quote in a new tab)

Normalization of pre-enrollment treatment burden

“Patients who were treated for <12 months prior to study enrollment had their 12-month treatment burden normalized based on the number of injections they received and the time period during which they received those injections” (opens the source at this quote in a new tab)

Minimal-fluid subgroup definition

“A subgroup of patients from the mid- and high-dose cohorts with minimal or no fluid at baseline, defined as CST values of ≤350 μm at screening (n = 9; CST, 205–298 μm) and minimal intraretinal or subretinal fluid reported in the study eye, was identified and analyzed separately.” (opens the source at this quote in a new tab)

Results

Participant disposition

Withdrawal and death of one participant

“One patient withdrew from the study after the week 16 visit due to personal concerns related to traveling during the ongoing coronavirus disease 2019 pandemic.” (opens the source at this quote in a new tab)
“The cause of death was listed as diverticulitis, which was a preexisting condition reported in the patient’s previous medical history prior to the start of the study that had resolved and was not being treated at the time of screening per the patient’s own report.” (opens the source at this quote in a new tab)

Baseline characteristics

Baseline characteristics: all 17 participants

Characteristic	Single-dose EYP-1901, 17 participants
Age, mean (range), years	“77.4 (67–94)”
Female, n (%)	“13 (76)”
BCVA, ETDRS letters, mean (range)	“69 (38–85)”
CST, µm, mean (range)	“299 (204–441)”
Time from diagnosis to enrollment, months, median (range)	“17 (4–74)”
Anti-VEGF injections in the prior 12 months, normalized, mean (range)	“8.6 (3–10)”

Efficacy results

Summary: DAVIO biologic activity

In DAVIO, 17 participants with previously treated wet age-related macular degeneration received a single EYP-1901 injection at 440 to 3090 μg, and 16 were included in efficacy analyses. Mean BCVA change from baseline was -1.8 letters at 6 months and -5.4 letters at 12 months, and mean CST change was +1.7 μm and +2.4 μm. At 12 months, 6 of 16 participants (37.5%) had lost 5 or more letters. Treatment burden, compared with a normalized pre-enrollment count, was reduced by 74% at 6 months and 71% at 12 months. Of 16 study eyes, 13 (81%), 8 (50%), and 5 (31%) required no additional anti-VEGF injection up to 3, 6, and 12 months, respectively. The study had no control arm, was open label, and was not powered for efficacy.

BCVA change from baseline

“A mean (range) BCVA change from baseline of +0.7 (−11 to +12), −5.2 (−51 to +10), −1.8 (−38 to +8), and −5.4 (−45 to +10) ETDRS letters was observed at 4, 5, 6, and 12 months, respectively, following administration of EYP-1901” (opens the source at this quote in a new tab)
“Among the 16 patients who completed the study, 6 (37.5%) had a loss of ≥5 letters from baseline in BCVA at 12 months, and 10 patients (62.5%) had a loss of <5 letters, no change, or a gain from baseline in BCVA at 12 months.” (opens the source at this quote in a new tab)

CST change from baseline

“A mean (range) CST change from baseline of +2.7 (−147 to +173), +60.5 (−91 to +227), +1.7 μm (−174 to +263), and +2.4 μm (−215 to +239) was observed at 4, 5, 6, and 12 months, respectively, following administration of EYP-1901” (opens the source at this quote in a new tab)

Treatment burden and injection-free rates

“When comparing the number of anti-VEGF injections before and after treatment with EYP-1901, the treatment burden was reduced by 74% at 6 months and 71% at 12 months” (opens the source at this quote in a new tab)
“The median time to first additional anti-VEGF treatment was 6.5 months. Thirteen eyes of 16 (81%) remained additional-injection free up to 3 months, 8 of 16 (50%) up to 6 months, and 5 of 16 (31%) up to 12 months” (opens the source at this quote in a new tab)

Subgroup: minimal or no fluid at screening

“In the subgroup of 9 eyes that had minimal or no fluid at screening, the mean change in BCVA from baseline was −0.4 letters (range, −12 to +8) at 6 months and −2.2 letters (range, −17 to +10) at 12 months.” (opens the source at this quote in a new tab)
“Sixty-seven percent did not require an additional injection up to 6 months and 56% up to 12 months. The median time to first additional anti-VEGF treatment among these eyes was 12 months.” (opens the source at this quote in a new tab)

Earlier company-reported 12-month treatment burden

“EYP-1901 Phase 1 DAVIO clinical trial continues clinically significant reduction in treatment burden of 74% at 12-months” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Summary of ocular TEAEs by dose

TEAEs through study end, n (%)	440 μg, 3 participants	1030 μg, 1 participant	2060 μg, 8 participants	3090 μg, 5 participants	Overall, 17 participants
Participants with 1 or more ocular TEAE	“3 (100.0)”	“0 (0.0)”	“6 (75.0)”	“4 (80.0)”	“13 (76.5)”
Participants with 1 or more ocular treatment-related TEAE	“1 (33.3)”	“0 (0.0)”	“4 (50.0)”	“1 (20.0)”	“6 (35.3)”
Conjunctival hemorrhage	“0 (0.0)”	“0 (0.0)”	“3 (37.5)”	“1 (20.0)”	“4 (23.5)”
Neovascular AMD	“1 (33.3)”	“0 (0.0)”	“3 (37.5)”	“0 (0.0)”	“4 (23.5)”
Retinal exudate	“0 (0.0)”	“0 (0.0)”	“0 (0.0)”	“3 (60.0)”	“3 (17.6)”

Ocular safety

“No dose-limiting toxicity was observed in this study.” (opens the source at this quote in a new tab)
“No patients experienced an ocular SAE or TEAE leading to discontinuation or death.” (opens the source at this quote in a new tab)
“There were no vitreous floaters, endophthalmitis, retinal detachment, insert migration into the anterior chamber, retinal vasculitis, posterior or anterior segment inflammation, vascular occlusive events, or ischemic optic neuropathy observed throughout the study.” (opens the source at this quote in a new tab)
“One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters.” (opens the source at this quote in a new tab)

Systemic safety

“Forty systemic, nonocular AEs were reported among 14 patients (82.4%).” (opens the source at this quote in a new tab)
“One nonocular TEAE, an increased laboratory value of γ-glutamyltransferase arising on day 58, was considered possibly treatment-related and mild.” (opens the source at this quote in a new tab)
“Two patients (11.8%) had SAEs during the study, including pneumonia in 1 patient and diverticulitis in the other, the latter resulting in death. In both patients, these SAEs occurred >6 months after receiving EYP-1901 at a time point when the study drug was undetectable in plasma.” (opens the source at this quote in a new tab)

Study limitations

Summary

DAVIO enrolled 17 participants across 4 dose cohorts (1 to 8 participants per cohort) at 11 sites in the United States, without a control arm or masking, and no formal sample size calculation was performed. Four participants in the planned 3090-μg cohort received fewer inserts than planned because of injector difficulties and were reassigned to lower-dose cohorts. Efficacy and treatment-burden analyses were descriptive, excluded 1 participant who withdrew after week 16, and were added post hoc, with pre-enrollment treatment burden normalized from historical records. The authors state that unmasked investigators may have been biased in deciding on supplemental injections. The eligibility criteria (3 or more prior injections of the same agent in 6 months, dosing 7 to 10 days after the last anti-VEGF injection) limit applicability to treatment-naive participants, and the doses tested differ from the 2.7-mg phase 3 dose. The publication was sponsored by EyePoint, and 2 authors were EyePoint employees.

Limitations stated by the authors

“Additionally, the study lacked a control group, meaning there was no comparison of the study drug with an existing therapy. Investigators were not masked to study enrollment, which may have biased their decision to administer supplemental injections during the study period. The study was not powered to make statistical comparisons.” (opens the source at this quote in a new tab)