Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene

Summary: The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene.

Detailed description: The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via IVT in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects will receive one single IVT injection of QR-421a or sham-procedure in one eye (subject's worse eye) and will be followed up for 48 weeks.
  Three dose levels of QR-421a will be evaluated: 50, 100, and 200 µg. Additional dose levels (eg, 25 or 400 µg) may be evaluated based on ongoing safety and efficacy data monitoring.
  Per dose cohort, a minimum of 4 subjects will be treated with QR-421a and a minimum of 2 subjects will receive the sham-procedure. The first subject in a dose cohort will receive QR-421a (open-label); subsequent subjects in the same dose cohort will be randomized to either QR-421a or sham-procedure.

Eligibility: Inclusion Criteria:
  1. Male or female, ≥ 18 years of age.
  2. Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
  3. An ERG result consistent with RP with Usher syndrome type 2 or NSRP.
  4. A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis upon Sponsor approval.
  5. A BCVA less than or equal to Logarithm of the Minimum Angle of Resolution (LogMAR) +0.2 in the worse eye.
  6. Semi-Automated Kinetic VF V4e (Octopus 900): Continuous area of central field greater than or equal to 10 degrees diameter (equivalent in area: 78.53981634 deg2) in both eyes.
  7. No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes (including outer segment [OS] thickness and volume, outer nuclear layer [ONL] thickness, total receptor (TR) thickness, EZ horizontal and vertical widths, apparent continuous EZ area, central macula thickness [CMT], grading of cystic macular lesions [CML] if any), as determined by the reading center.
  8. Reliable perimetry measurements in both eyes, as described in the Study Reference Manual and determined by the reading center.
  9. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.
  Exclusion Criteria:
  1. Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who are compound heterozygous for mutations in exon 13.
  2. Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who are homozygous for mutations in exon 13.
  3. Presence of pathogenic mutations in genes (other than the USH2A gene) associated with Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or syndromes.
  4. Any contraindication to IVT injection according to the Investigator's clinical judgment and international guidelines.
  5. Nystagmus or unstable fixation.
  6. Amblyopia.
  7. Prior receipt of intraocular surgery or procedure or IVT injection within 12 weeks prior to study start or planned intraocular surgery or procedure during the course of the study.
  8. Any prior treatment with genetic therapy.

Relevance to patient case: not relevant