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Clinical Trials/NCT05158296
NCT05158296
Terminated
Phase 2

A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety and Tolerability of Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene (Sirius)

Laboratoires Thea15 sites in 4 countries7 target enrollmentStarted: December 8, 2021Last updated:
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ConditionsRetinitis PigmentosaUsher Syndrome Type 2Deaf BlindRetinal DiseaseEye DiseasesEye Diseases, HereditaryEye Disorders CongenitalVision Disorders
InterventionsUltevursenSham-procedure
DrugsUltevursen

Overview

Phase
Phase 2
Status
Terminated
Enrollment
7
Locations
15
Primary Endpoint
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA)
OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Overview

Brief Summary

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

The below dose levels of ultevursen will be evaluated with the loading dose administered at Day 1 and maintenance dose administered at Month 3 and every 6 months thereafter:

  1. Loading dose of 60 µg, maintenance dose of 60 µg
  2. Loading dose of 180 µg, maintenance dose of 60 µg

Dose levels will include subjects randomized to sham-procedure or treatment with ultevursen.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

Subject, site staff (study coordinator, imaging technician, etc) and Investigator will be completely masked. Physician performing IVT and post-IVT monitoring will know if subject is receiving sham or treatment, but will be masked to the dose level. Pharmacist is the only site staff that will be completely unmasked.

Eligibility Criteria

Ages
12 Years to — (Child, Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Male or female, ≥ 18 years of age OR a minor (12 to \< 18 years) with permission from a parent or legal guardian. The lower age limit for pediatric populations is subject to local regulatory and ethics committee requirements.
  • •An adult willing to comply with the protocol, follow study instructions, attend study visits as required and willing and able to complete all study assessments. OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions, and attend study visits with the subject as required.
  • •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 treatment eye using the mean BCVA reading at screening. Subjects with a mean BCVA between \>68 and ≤73 letters will be allowed with documented historic evidence of a BCVA equivalent decline of \>5 letters in both eyes.
  • •BCVA between ≥30 and ≤73 letters (approximate Snellen equivalent 20/250 - 20/40) in the contralateral eye (CE), using the mean BCVA reading at Screening.
  • •A difference in mean BCVA readings at Screening between the TE and CE of
  • •≤10 letters (based on ETDRS). BCVA differences between eyes that are greater than 10 letters may be allowed however, the Investigator should discuss the case with the Medical Monitor.
  • •Stable BCVA in the TE and CE, defined as 2 separate BCVA measurements at Screening that fall within ≤ 5 letters for each respective eye.
  • •A visible EZ layer on SD-OCT in the TE, as determined by the Investigator.

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.
  • •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. Note: The confirmed presence of homozygous or compound heterozygous known disease-causing mutations in other genes involved in recessive retinal dystrophies (RD), or the confirmed presence of known disease-causing mutations in genes involved in dominant or X-linked retinal dystrophies is exclusionary.
  • •Presence of any significant ocular (in either eye) or non-ocular disease/disorder (or medication and/or laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study. This includes but is not limited to a subject who has uncontrolled cystoid macular edema (CME). CME is permissible if stable for 3 months (with or without treatment). Past CME is permissible if resolved for more than 1 month.
  • •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 either 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 or planned intraocular surgery or procedure in either eye during the course of the study. For YAG laser treatment of a posterior capsular opacity, receipt within 1 month prior to Screening or planned procedure in either eye during the course of the study.

Arms & Interventions

Ultevursen 60/60 µg

Experimental

60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter

Intervention: Ultevursen (Drug)

Ultevursen 180/60 µg

Experimental

180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter

Intervention: Ultevursen (Drug)

Sham-procedure

Sham Comparator

Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter

Intervention: Sham-procedure (Other)

Outcomes

Primary Outcomes

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA)

Time Frame: 18 months of treatment versus sham-procedure

Mean change from baseline in best corrected visual acuity(BCVA) based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart

Secondary Outcomes

  • Proportion of Patients Who Maintain Vision Defined by BCVA Loss Less Than 15 Letters (ETDRS)(27 months)
  • Change From Baseline in Other Analyses of Best Corrected Visual Acuity (BCVA)(27 months)
  • Change From Baseline in Full-field Stimulus Threshold (FST)(27 months)
  • Cmax of Ultevursen in Serum(27 months)
  • Ocular and Non-ocular Adverse Events (AEs)(27 months)
  • Change From Baseline in Ellipsoid Zone (EZ) Area and Width as Imaged by Spectral Domain Optical Coherence Tomography (SD-OCT)(27 months)
  • Change From Baseline in Low Luminance Visual Acuity (LLVA)(27 months)
  • Change From Baseline in Microperimetry(27 months)
  • Change From Baseline in PRO Measures(27 months)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (15)

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