Actively Recruiting // Clinical Trials // Inherited Retinal Degeneration // Kimberly Stepien // Retinitis Pigmentosa // Feb 08 2022

A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety, and Tolerability of QR-421a in Subjects with Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene with Advanced Vision Loss (SIRIUS)

  • Sponsor: ProQR Therapeutics
  • Principal Investigator: Kimberly Stepien
  • Study Coordinator: Nickie Stangel

Study Objective:

To evaluate the efficacy safety and tolerability of QR-421a administered via intravitreal injection  in subjects with Retinitis Pigmentosa due to mutations in exon 13 of the USH2A gene with advanced vision loss.

Study Design:

The study involves 10 visits over the course of 1 year. Subjects will be randomized to one of three treatment groups which will be administered on Day 1, Month 3, and every 6 months thereafter.

Inclusion Criteria:

  • Male or female, ≥ 18 years of age OR a minor (12 to < 18 years) with permission from a parent or legal guardian.
  • Clinical presentation consistent with RP with Usher syndrome type 2 or nonsyndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
  • A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis at screening.
  • BCVA between ≥30 and ≤68 letters (approximate Snellen equivalent 20/250 – 20/50) in the study eye
  • Impairment of Visual Field (VF) in the opinion of the Investigator as determined by perimetry, with a continuous area of central field greater than or equal to 10 degrees diameter in each meridian as measured by a size V4e target, and a mean defect of ≥ 10 dB, in the study eye.

Exclusion Criteria:

  • Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who have monoallelic exon-13 mutations.
  • Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations.
  • History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in either eye.
  • Presence of any active ocular infection in either eye.
  • Presence of any of the following lens opacities in the study eye: cortical opacity ≥
  • +2, posterior subcapsular opacity ≥ +2, or a nuclear sclerosis ≥ +2, and which are: 1) clinically significant in the opinion of the Investigator, 2) would adequately prevent clinical and photographic evaluation of the retina.
  • History of amblyopia in the study eye that resulted in significant vision loss, in the opinion of the Investigator.
  • Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection other or planned intraocular surgery or procedure during the course of the study.
  • Current treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to steroid implants, cytostatics, interferons, tumor necrosis factor (TNF)-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system). Subjects that have been treated with systemic steroids within the past 12 months or that require intermittent use of topical steroids may be considered for inclusion following approval by the Medical Monitor.
  • A history of glaucoma or an IOP greater than 24 mmHg in either eye that is not controlled with medication or surgery.
  • Use of any investigational drug or device within 90 days or 5 half-lives preceding the first dose of study medication, whichever is longer, or plans to participate in another study of an investigational drug or device during the course of the study.
  • Any prior treatment with genetic or stem-cell therapy for ocular or non-ocular disease.
  • History of malignancy within 2 years prior to Screening, except adequately treated squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
  • Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.


Contact Nickie Stangel with questions, 608-263-8783. For more information about this study: