PRISM phase 2b population extension
44 evidence topics · 13 sources
Objective
Objective of the Population Extension cohort
Location and study date
Registry dates for the overall PRISM trial
| Milestone | Registry record |
|---|---|
| Study start (actual) | “2021-12-09” |
| Primary completion (estimated) | “2027-03” |
| Study completion (estimated) | “2031-01” |
Enrollment completion and data cutoffs
Study design
Open-label, sequentially assigned, two-dose cohort
Registered substudies and long-term follow-up
Eligibility criteria
Key inclusion criteria for the Population Extension cohort
| Criterion | Quoted slide text |
|---|---|
| Prior anti-VEGF injections | “1–6 in prior 12 m (≥1 last 12 weeks)” |
| CST at screening | “No minimum or maximum” |
| BCVA at screening | “34–83 ETDRS letters” |
Registered inclusion criteria for the main trial
Treatment
Scheduled aflibercept loading doses
Prophylactic corticosteroid regimens
Supplemental aflibercept injection criteria
Study outcomes
Rationale for using treatment-emergent adverse events as the primary endpoint
Key endpoints presented for the Population Extension cohort
“Safety and tolerability” (opens the source at this quote in a new tab)
“Annualized anti-VEGF injection rate” (opens the source at this quote in a new tab)
“% requiring supplemental aflibercept injection” (opens the source at this quote in a new tab)
“Change from baseline in BCVA and CST” (opens the source at this quote in a new tab)
Treatment burden benchmark against projected on-label aflibercept
Rationale for endpoint selection
No evidence found.
Statistical analysis description
Number of participants (Planned and analyzed)
Planned and enrolled participants
Description of analysis sets
Handling of missing and confounded BCVA assessments at week 52
Kaplan-Meier estimates at the September 2024 data cutoff
Results
Participant disposition
Corticosteroid regimen completion at week 24
Discontinuations
No evidence found.
Baseline characteristics
Demographics and baseline disease characteristics by dose
| Characteristic | 4D-150 3E10 vg/eye (N=30) | 4D-150 1E10 vg/eye (N=15) | Total (N=45) |
|---|---|---|---|
| Mean ±SD age, years | “77 ±7.7” | “78 ±8.6” | “77 ±7.9” |
| Female, n (%) | “20 (67)” | “6 (40)” | “26 (58)” |
| Mean ±SD BCVA, ETDRS letters | “71 ±9.9” | “73 ±8.8” | “72 ±9.5” |
| Mean ±SD central subfield thickness | “336 ±135.0” | “314 ±70.8” | “329 ±117.1” |
| Mean ±SD time since diagnosis, years | “1.8 ±3.5” | “0.7 ±0.9” | “1.4 ±2.9” |
| Mean ±SD actual anti-VEGF injections in prior 12 months | “4.4 ±2.0” | “4.3 ±2.1” | “4.4 ±2.0” |
Recently diagnosed subgroup at baseline
| Characteristic | Phase 2b recently diagnosed subgroup, 3E10 vg/eye |
|---|---|
| Mean injections in last 12 months | “2.7” |
| Mean CST | “304 µm” |
| Mean time since diagnosis | “2.4 months” |
Efficacy results
Summary: treatment burden, visual acuity, and anatomy through 2 years
At the 2-year analysis (data cutoff May 18, 2026), participants receiving 3E10 vg/eye (n=30) received a mean of 2.7 supplemental injections, a 78% reduction versus 12.0 injections projected for on-label aflibercept 2 mg every 8 weeks, and 46% were injection-free; the 1E10 vg/eye arm (n=15) received a mean of 3.7 injections (69% reduction). In the recently diagnosed subgroup at 3E10 vg/eye (n=15), the mean was 1.6 injections (87% reduction) and 66% were injection-free. The reduction at 3E10 vg/eye declined from 83% at 52 weeks (0.97 mean injections, 57% injection-free) and 82% at 1.5 years to 78% at 2 years. Mean BCVA change at week 52 was +2.2 letters with censoring of confounded assessments and +1.0 letter without censoring; mean CST change was -11 µm. At 2 years, BCVA and CST were described as maintained, with numerical values shown only in figures.
Treatment burden through 2 years
Injection-free proportions and lower-dose comparison at 2 years
| Outcome at 2 years | Quoted slide text |
|---|---|
| Phase 2b broad, 0 to 1 supplemental injection | “>50% of Participants Required 0-1 Supplemental Injection” |
| Phase 2b recently diagnosed, injection-free | “66% of Participants were Supplemental Injection-Free” |
| Phase 2b broad, 1E10 vg/eye, reduction and mean cumulative injections | “69%”and “3.7” |
| Phase 2b recently diagnosed, 1E10 vg/eye, reduction and mean cumulative injections | “73%”and “3.3” |
| Phase 2b broad, 3E10 vg/eye, injection-free | “46%” |
Mean cumulative supplemental injections through 1.5 years
| Population and dose | Through year 1 | Through year 1.5 |
|---|---|---|
| Phase 2b broad, 3E10 vg/eye (n=30) | “1.0 (83% reduction)” | “1.6 (82% reduction)” |
| Phase 2b broad, 1E10 vg/eye (n=15) | “1.4 (77% reduction)” | “2.4 (73% reduction)” |
| Recently diagnosed, 3E10 vg/eye (n=15) | “0.3 (94% reduction)” | “0.7 (92% reduction)” |
| Recently diagnosed, 1E10 vg/eye (n=11) | “1.4 (77% reduction)” | “2.1 (77% reduction)” |
Supplemental injections by 6-month interval
52-week results at the planned Phase 3 dose
Earlier Kaplan-Meier estimates at week 52 in the broad cohort (September 2024 data cutoff)
Earlier Kaplan-Meier estimates at week 52 in the recently diagnosed cohort (September 2024 data cutoff)
24-week landmark results
| Outcome, average of weeks 20 and 24 | 4D-150 3E10 vg/eye | 4D-150 1E10 vg/eye |
|---|---|---|
| Adjusted mean (95% CI) change in BCVA, ETDRS letters | “+3.5 (1.1, 5.8)” | “–2.2 (–5.9, 1.4)” |
| Adjusted mean (95% CI) change in CST, µm | “–9.2 (–30.8, 12.4)” | “+6.9 (–26.7, 40.6)” |
Aqueous humor aflibercept concentrations across 3E10 vg/eye cohorts
Supplemental injections through 32 weeks at the September 2024 data cutoff
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
Safety at the planned Phase 3 dose across PRISM through 2 to more than 4 years
Steroid prophylaxis completion across Phase 3-dose participants
Endophthalmitis attributed to a supplemental aflibercept injection
Inflammation at the 24-week analysis, including the lower dose
Treatment-emergent adverse event frequencies
No evidence found.
Study limitations
Summary
The Population Extension is an open-label, non-randomized cohort of 45 participants (30 at 3E10 vg/eye and 15 at 1E10 vg/eye) with sequential dose assignment and no concurrent aflibercept control; 13 of the 30 participants at 3E10 vg/eye came from an alternative steroid cohort, and three different prophylactic corticosteroid regimens were used. Treatment burden reduction is calculated against a projected on-label aflibercept every-8-weeks schedule (6.0 injections at 52 weeks and 12.0 at 2 years) derived from a single-arm model, not against observed injections in a comparator arm, and the 4D-150 arms received scheduled aflibercept at Day -7 and Day 28. Reported values changed across data cutoffs for the same timepoint (for example, 70% injection-free through 52 weeks by Kaplan-Meier estimate in September 2024 versus 57% at the January 2025 cutoff), and the 3E10 vg/eye reduction declined from 83% at 1 year to 78% at 2 years, with 46% injection-free at 2 years. The week 52 BCVA gain was +2.2 letters with censoring of cataract or surgery-confounded assessments and +1.0 letter without censoring; 2-year BCVA and CST results were presented only as figures. The recently diagnosed subgroup most comparable to the Phase 3 population includes only 15 participants. Aqueous humor aflibercept was below the limit of quantitation at any visit in 14 of 43 evaluable participants (33%). Pooled safety across 71 participants at 3E10 vg/eye is too small to detect uncommon events, adverse event frequency tables have not been released, and no peer-reviewed full publication or patient-reported outcome data were identified.