First Patients Dosed in Gene Therapy Trial for Usher Syndrome, Retinitis Pigmentosa

This content originally appeared on our sister site, Ophthalmology Times.

The first patients have been dosed in the phase 2/3 Sirius and Celeste clinical trials of the investigational RNA therapy QR-421a (ProQR Therapeutics) for people with USH2A mediated retinitis pigmentosa (RP) and Usher syndrome.

“Retinitis pigmentosa (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”, investigator David Birch, PhD, Retina Foundation of the Southwest, Dallas, Texas. “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.”

Aniz Girach, MD, chief medical officer of ProQR, added that the company was pleased to bring its second RNA therapy into potentially the final stage of clinical testing.

READ MORE: A Snapshot of Ophthalmologic Therapies in Development

“In a previous clinical study, QR-421a appeared to be well tolerated and demonstrated concordant benefit in multiple measures of vision in treated eyes compared to untreated,” Girach said. “Our goal is that the Sirius and Celeste studies further validate QR-421a’s ability to stabilize vision loss in people with USH2A mediated retinitis pigmentosa and Usher syndrome.”

About the Sirius and Celeste Clinical Trials

Sirius and Celeste are two double-masked, randomized, sham controlled, 24-month, multiple dose studies to evaluate whether QR-421a is effective at stopping vision loss and whether it is safe and well-tolerated.

Adults and children (age 12 and up) with vision loss due to mutations in exon 13 of the USH2A gene will be enrolled in one of the studies, depending on baseline vision. In both studies participants are randomly assigned to three parallel study arms. In the two treatment arms, participants receive intravitreal injections with QR-421a at different doses (180 μg loading dose and 60 μg maintenance doses or 60 μg loading dose and 60 μg maintenance doses).

In the third sham control arm the intravitreal injections are mimicked but no injection or study medication is given.

The Sirius study is planned to enroll 81 participants with advanced vision loss (baseline best corrected visual acuity (BCVA) of worse than 20/40). The primary endpoint in the study is mean change from baseline in BCVA at 18 months in the treated arms compared to the control arm.

The Celeste study is planned to enroll 120 participants with early to moderate vision loss (baseline BCVA of equal or better than 20/40). The primary endpoint in the study is mean change from baseline in static perimetry at 12 months in the treated arms compared to the control arm.