QR‐421a RNA therapy in retinitis pigmentosa due to mutations in USH2A: Stellar trial Phase[AP1] 1b/2 interim results
Bibliographic record
Abstract
Abstract Purpose To report Phase 1b/2 interim results of QR‐421a RNA therapy promoting USH2A exon 13 skipping. USH2A exon 13 mutations lead to non‐syndromic Retinitis Pigmentosa & Usher syndrome type 2. Methods Stellar ( NCT03780257 ) is a 24‐month, multicenter Phase 1b/2 single‐dose trial assessing 3 dose levels (50, 100, 200 μg) of QR‐421a in patients aged ≥18 years with biallelic USH2A pathogenic mutations with at least one in exon 13. Cohorts 1 & 2 included subjects randomized to sham‐procedure or QR‐421a. Primary endpoints: frequency & severity of adverse events (AEs). Secondary endpoints: change in best‐corrected visual acuity (BCVA), static perimetry & ellipsoid zone [EZ] area. Results 20 subjects were enrolled, 14 received QR‐421a & 6 received sham. Response to QR‐421a was similar for all doses. No serious AE or inflammation was observed. Two subjects had worsening of pre‐existing conditions: one with cataracts (not treatment‐related) & one with cystoid macular edema (being managed with standard care). BCVA stabilization was observed in QR‐421a‐treated eyes (TE), versus a decline in untreated eyes (UE). At week 48, mean BCVA benefit was 6.0 & 9.3 letters in all QR‐421a‐treated & advanced subjects (n = 6; baseline BCVA of <70 letters) respectively. No BCVA benefit was observed in sham‐treated eyes (SE). Mean change from baseline of the EZ‐area was +15.0% in TE, –26.4% in UE, & –12.5% in SE at week 24. For static perimetry at week 12, the mean number of locations (loci) that improved by ≥7 dB compared to baseline was 9.2 loci versus 6.1 loci in TE versus UE in all QR‐421a‐treated subjects & 12.9 loci versus 6.9 loci in early moderate‐stage subjects (n = 8; baseline BCVA of ≥70 letters). SE responded similarly to UE. Conclusions QR‐421a was well tolerated & demonstrated evidence of disease stabilization in visual acuity, & improvements in retinal sensitivity & retinal structural imaging data. An open‐label extension trial & 2 Phase 2/3 trials are planned.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".