Ultevursen news update Final phase trials started for USH2A mediated RP and Usher syndrome

Sirius and Celeste are the names of our two Phase 2/3 studies of ultevursen (previously named QR-421a) an experimental RNA therapy in people with USH2A associated retinitis pigmentosa (RP) and Usher syndrome. We have advanced to the final phase of clinical development following the positive readout of our Phase 1/2 Stellar in March 2021.

Usher syndrome is the leading cause of combined deafness and blindness. People with USH2A mediated Usher syndrome are usually born with hearing loss and start to have progressive vision loss during adulthood. The vision loss can also occur without hearing loss in a disease called retinitis pigmentosa, or RP.

“RP and Usher syndrome associated with USH2A are inherited retinal diseases that can lead to blindness because there is no treatment available to stop the progressive vision loss. These are the first, potentially pivotal trials for these conditions, that we see as a promising milestone that brings hope to the RP and Usher syndrome communities.”

David Birch, Ph.D., Scientific Director at the Retina Foundation of the Southwest and investigator in the Sirius and Celeste studies.

What will Sirius and Celeste look like?

Sirius and Celeste, are two double-masked, randomized, sham controlled, 24-month, multiple dose studies to evaluate whether ultevursen are effective at stopping vision loss and whether they are safe and well-tolerated.

Adults and children (age 12 and up) with RP due to mutations in exon 13 of the USH2A gene will be enrolled in one of the studies. In both studies, participants are randomly assigned to three parallel study arms. In the two treatment arms participants receive intravitreal injections with ultevursen at different dose levels. In the third sham control arm the intravitreal injections are mimicked but no injection or study medication is given.

Sirius study

The Sirius study is for people with advanced vision loss (baseline best corrected visual acuity (BCVA) of worse than 20/40) and the primary endpoint is mean change in BCVA from baseline at 18 months in the treated arms compared to the control arm. Approximately 80 individuals will be enrolled in the Sirius study.

Celeste study

The Celeste study is for people with early to moderate vision loss (baseline BCVA of equal or better than 20/40) and the primary endpoint is mean change in static perimetry from baseline at 12 months in the treated arms compared to the control arm. Approximately 120 individuals will be enrolled in the Celeste study.

“We are pleased to bring our second RNA therapy into potentially the final stage of clinical testing. In a previous clinical study, ultevursen appeared to be well tolerated and demonstrated concordant benefit in multiple measures of vision in treated eyes compared to untreated. Our goal is that the Sirius and Celeste studies further validate ultevursen's ability to stabilize vision loss in people with USH2A mediated retinitis pigmentosa and Usher syndrome.”

Aniz Girach, M.D., Chief Medical Officer of ProQR

Want to learn more about Sirius and Celeste?

Clinical trials are used by researchers to find out whether new medicines are safe and well-tolerated. Learn more about clinical trials and participation.

Visit our dedicated Sirius or Celeste webpage to learn more.

For more information on our wider work in USH2A, please visit our dedicated ultevursen webpage.