NEGATIVE RESULTS

UCSF's REAGIR trial misses primary endpoint for Rose Bengal eye therapy

The Phase 3 REAGIR trial found adjunctive Rose Bengal photodynamic therapy did not beat standard antimicrobial treatment on visual acuity in infectious keratitis, with only a non- subgroup signal in Fusarium infection.

The REAGIR Phase 3 trial of adjunctive Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) added to standard antimicrobial treatment did not separate from standard therapy alone on its primary 6-month visual acuity endpoint in infectious keratitis.

By AppliedXLJuly 22, 2026Trial NCT05110001

Executive Summary

A Phase 3 trial testing whether adding a light-activated antimicrobial therapy to standard treatment for infectious corneal ulcers improves vision found no separation from standard treatment alone on its primary endpoint.
The trial compared standard antimicrobial eye treatment with and without the adjunctive light-activated therapy in patients with fungal, amoebic, or culture-negative corneal ulcers, using visual acuity at six months as the measure of success.
Sponsor communications highlighted a favorable but statistically inconclusive trend in one fungal-species subgroup, a secondary and underpowered cut of the data that does not offset the negative primary result.
Serious ocular complications, including cases requiring corneal transplant surgery, occurred somewhat more often in the treatment arm than in the standard-therapy arm, a signal worth weighing against any future use of the combination.
The developer has signaled plans to pursue a new, differently designed trial after discussions with regulators, rather than to advance the current data package as registration-supporting.

The result

REAGIR (NCT05110001), a 330-patient, randomized, quadruple-masked Phase 3 trial run by the University of California, San Francisco with sites in Brazil and India, tested whether adding RB-PDAT, a rose bengal dye activated by green light, to standard antimicrobial treatment (chlorhexidine, moxifloxacin, or natamycin depending on suspected pathogen) improved outcomes in infectious keratitis, corneal ulcers caused by fungi, amoeba, or unidentified organisms. The trial's posted primary outcome measure, best spectacle-corrected visual acuity at 6 months, showed no separation between the RB-PDAT arm and the standard-therapy-alone arm across the full enrolled population, and the developer's own July 22, 2026 disclosure reports the trial did not meet its primary endpoint. NCT05110001+1

How it was tested

The design was a two-arm, randomized, quadruple-masked comparison: one arm received standard topical antimicrobial therapy alone, the other received the same standard therapy plus RB-PDAT. Natamycin served as the antimicrobial comparator for fungal cases specifically. The trial enrolled its full target of 330 patients, reached its primary completion date of January 31, 2025, and moved to Active, not recruiting status as enrollment closed on schedule. Secondary measures tracked visual acuity at 3 weeks, 3 months, and 12 months, and scar size through 12 months. NCT05110001

The subgroup signal

Within the negative overall result, a subgroup of patients with Fusarium-species fungal infection showed a directionally favorable trend that did not reach statistical significance (p=0.1). That figure was drawn from a secondary, species-level cut of the data rather than the trial's prespecified primary comparison, and the developer's public materials were flagged for leaning on that subgroup and on post-hoc framing rather than the primary result itself. A companion account of the same trial's 12-month data, presented as a poster in May 2026, describes the same pattern: no statistically significant benefit on visual acuity, scar size, or perforation rates, with the Fusarium trend favorable, an Aspergillus subgroup trending unfavorable, and a small Acanthamoeba subgroup trending favorable. VisiRose

Safety findings

Posted adverse-event data show serious events, including corneal perforation and cases requiring therapeutic corneal transplant surgery, in 36 of 165 patients at risk in the RB-PDAT arm versus 31 of 165 in the standard-therapy arm. One death occurred in the standard-therapy arm and none in the RB-PDAT arm. The trial's own risk profile shows a primary completion date that moved three times, cumulative delays of 211 days, and no registry update for an extended stretch before this year's disclosures, a pattern the trial's own operational history documents even as it reached its enrollment target and completed on the revised schedule. NCT05110001

What's next for the program

The developer's public plans point toward a new Phase 2b/3 trial following a pre-IND meeting with the FDA, rather than continued reliance on the REAGIR data package as sufficient on its own. That signals an acknowledgment that the current primary result does not support advancing without further study. VisiRose

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.