B-421a-006 is a 24-month, double-masked, randomized, sham-controlled, multicenter study to evaluate the safety, tolerability, and efficacy of ultevursen in subjects with RP due to mutations in exon 13 of the USH2A gene.
- Principal Investigator: Kimberly Stepien
- Study Coordinator: Nickie Stangel
- Study Sponsor: Laboratoires THEA
Study Objective
Ultevursen is designed to target specifically mutations in exon 13 of the USH2A gene resulting in the production of a functional (shorter) usherin protein. It is hypothesized that the production of usherin protein in the retina can potentially slow or stop the progression of photoreceptor degradation and as such, preserve visual function in patients.
Study Design
Subjects will be randomized in a 2:1 ratio to 1 of 2 treatment groups: ultevursen or sham. Randomization will be stratified by EZ width (<5mm, ≥5mm) and phenotype (syndromic, non-syndromic) at screening and by region of the study sites (North/South America, Other). Subjects randomized to the active treatment group will receive therapy with ultevursen administered via intravitreal (IVT) injection in the treatment eye (TE) on Day 1 and at Months 6, 12, and 18. Subjects randomized to sham will undergo a sham procedure in the TE at these corresponding timepoints.
Subjects will have up to 10 visits with a screening period of up to 12 weeks and a treatment period of up to 24 months.
Inclusion Criteria:
1. An adult (≥18 years) willing and able to provide informed consent for participation prior to performing any study related procedures OR A minor (8 to <18 years) able to provide age-appropriate assent for study participation with a parent or legal guardian willing and able to provide written permission for the subject’s participation prior to performing any study related procedures.
2. A molecular diagnosis of biallelic disease causing variants (pathogenic or likely pathogenic) in the USH2A gene where at least one of the variants is located on exon 13. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval
3. Clearly visible and measurable EZ width of ≥2.5 mm in both horizontal and vertical scans in both eyes as measured by SD-OCT and based on the assessment of the CRC.
4. BCVA ≥55 letters based on ETDRS (equivalent to 20/80 based on Snellen notation, or logMAR +0.6) in both eyes.
5. At screening, reliable measurements in MP and SP.
6. No visually significant ocular media opacities and adequate pupillary dilation to permit good quality retinal visibility or imaging in either eye, as assessed by the Investigator.
7. Non-pregnant and non-breastfeeding subjects. WOCBP and fertile males must comply with using highly effective methods of contraception (see Section 14.2 for definitions of WOCBP and fertile males and details on highly effective contraception methods). Women of non[1]childbearing potential may be included without the use of adequate birth control, provided they meet the entry criteria for the study.
Exclusion Criteria:
1. Presence of any of the following lens opacities in the TE based on the AREDS lens grading scale: 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.
2. History of amblyopia in the TE that has resulted in vision loss, in the opinion of the Investigator.
3. A history of glaucoma or an IOP greater than 24 mmHg in the TE that is not controlled with medication or surgery at the time of informed consent.
4. Use of any investigational drug or device within 90 days or 5 half lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the study.
5. Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.
6. Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
7. Current chronic treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to steroid implants, chronic systemic steroids, cytostatics, interferons, TNF-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system). Subjects who have been treated on a short course of systemic steroids within the past 12 months or who require intermittent use of topical steroids may be considered for inclusion following approval by the Medical Monitor.
8. Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine [Plaquenil®], tamoxifen, phenothiazines, ethambutol, digoxin, and aminoglycosides).
9. History of malignancy within 5 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.
Contact Nickie Stangel with questions at (608) 263-8783
For more information about this study, please visit clinicaltrials.gov