Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05158296
Other study ID # PQ-421a-003
Secondary ID 2021-002729-74
Status Active, not recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date December 8, 2021
Est. completion date December 2024

Study information

Verified date September 2022
Source ProQR Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 180 µg, maintenance dose of 60 µg 2. Loading dose of 60 µg, maintenance dose of 60 µg Dose levels will include subjects randomized to sham-procedure or treatment with ultevursen.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 81
Est. completion date December 2024
Est. primary completion date December 2024
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility Inclusion Criteria: 1. 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. 2. 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. 3. Clinical presentation consistent with RP with Usher syndrome type 2 or nonsyndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations. 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 at screening. 5. 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. 6. 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. 7. 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. 8. Stable BCVA in the TE and CE, defined as 2 separate BCVA measurements at Screening that fall within = 5 letters for each respective eye. 9. A visible EZ layer on SD-OCT in the TE, as determined by the Investigator. 10. No limitations to SD-OCT image collection that would prevent high quality, reliable images from being obtained in both eyes, as determined by the Investigator. 11. Reliable BCVA, perimetry, and other measurements in both eyes, as described in the Study Reference Manual and Imaging Manual and determined by the Investigator. 12. No visually significant ocular media opacities and adequate pupillary dilation to permit good quality retinal imaging in both eyes, 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 have monoallelic exon-13 mutations. 2. Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations. 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. 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. 4. 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. 5. History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in either eye. 6. Presence of any active ocular infection in either eye. 7. 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. 8. History of amblyopia in either eye that resulted in significant vision loss, in the opinion of the Investigator. 9. 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. 10. 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. 11. A history of glaucoma or an IOP greater than 21 mmHg in either eye that is not controlled with medication or surgery. IOP measurements between 21 and 24 mmHg may be allowed however, the Investigator should discuss the case with the Medical Monitor. 12. 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. 13. Any prior treatment with genetic or stem-cell therapy for ocular or non-ocular disease. 14. 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. 15. Known hypersensitivity to antisense oligonucleotides or any constituents of the injection. 16. Pregnant and breastfeeding subjects. Females of childbearing potential and males must comply with using highly effective methods of contraception as defined in the protocol. Women of non-childbearing potential may be included without the use of adequate birth control.

Study Design


Intervention

Drug:
Ultevursen
RNA antisense oligonucleotide for intravitreal injection
Other:
Sham-procedure
Sham-procedure (no experimental drug administered)

Locations

Country Name City State
Germany Universitaetsklinikum Tuebingen Department für Augenheilkunde Tuebingen
Netherlands RadboudUMC Nijmegen
Netherlands Het Oogziekenhuis Rotterdam Rotterdam
United Kingdom Oxford Eye Hospital Headington Oxford
United Kingdom Moorfields Eye Hospital London
United States University of Michigan, Kellogg Eye Center Ann Arbor Michigan
United States Emory Eye Center Atlanta Georgia
United States Wilmer Eye Institute, Johns Hopkins Hospital Baltimore Maryland
United States Center for Clinical Research Operations, Massachusetts Eye and Ear Boston Massachusetts
United States Retina Foundation of the Southwest Dallas Texas
United States University of Wisconsin - Madison Madison Wisconsin
United States University of Miami, Bascom Palmer Eye Institute Miami Florida
United States Columbia University New York New York
United States Shiley Eye Institute - UC San Diego San Diego California
United States University of California, San Francisco San Francisco California

Sponsors (1)

Lead Sponsor Collaborator
ProQR Therapeutics

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Mean change from baseline in BCVA Mean change from baseline in best corrected visual acuity(BCVA) based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart 18 months of treatment versus sham-procedure
Secondary Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters (ETDRS) Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters based on ETDRS 27 months
Secondary Change from baseline in other analyses of BCVA Change from baseline in other analyses of BCVA 27 months
Secondary Change from baseline in ellipsoid zone (EZ) area and width as imaged by spectral domain optical coherence tomography (SD-OCT) Change from baseline in ellipsoid zone (EZ) area and width as imaged by spectral domain optical coherence tomography (SD-OCT) 27 months
Secondary Change from baseline in Low Luminance Visual Acuity (LLVA) Change from baseline in Low Luminance Visual Acuity (LLVA) 27 months
Secondary Change from baseline in Microperimetry Change from baseline in Microperimetry 27 months
Secondary Change from baseline in Full-field Stimulus Threshold (FST) Change from baseline in Full-field Stimulus Threshold (FST) 27 months
Secondary Change from baseline in PRO measures As assessed by the Veteran Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-20), Patient Global Impressions of Severity (PGI-S) and Patient Global Impressions of Change (PGI-C) 27 months
Secondary Ocular and non-ocular adverse events (AEs) Ocular and non-ocular adverse events (AEs) 27 months
Secondary Cmax of ultevursen in serum Maximum concentration (Cmax) of ultevursen in serum 27 months
See also
  Status Clinical Trial Phase
Recruiting NCT01432847 - Cell Collection to Study Eye Diseases
Completed NCT04983914 - Retrospective NIS to Evaluate the Patient Benefit of TES
Recruiting NCT03845218 - Retinitis Pigmentosa Clinical Measures and Repeatability Testing of Potential Outcome Measures
Completed NCT00231010 - Molecular Genetics of Retinal Degenerations
Active, not recruiting NCT04611503 - PDE6A Gene Therapy for Retinitis Pigmentosa Phase 1/Phase 2
Completed NCT02909985 - Visual Activity Evoked by Infrared in Humans After Dark Adaptation N/A
Recruiting NCT01914913 - Clinical Study to Evaluate Safety and Efficacy of BMMNC in Retinitis Pigmentosa Phase 1/Phase 2
Completed NCT01949623 - Biomarkers In Retinitis Pigmentosa (BIRP) N/A
Completed NCT01835002 - Transcorneal Electrical Stimulation - Multicenter Safety Study N/A
Completed NCT00407602 - Argus® II Retinal Stimulation System Feasibility Protocol N/A
Completed NCT00515814 - Retina Implant Pilot Trial to Evaluate Safety & Efficacy in Blind Patients Having Degenerated Photo-receptors N/A
Completed NCT00100230 - DHA and X-Linked Retinitis Pigmentosa Phase 2
Active, not recruiting NCT00378742 - Repository for Inherited Eye Diseases
Terminated NCT05085964 - An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa Phase 2
Recruiting NCT05805007 - Safety and Tolerability Study of Gene Editing Drug ZVS203e in Participants With Retinitis Pigmentosa Early Phase 1
Recruiting NCT06291935 - Safety and Tolerability of Intravitreal Administration of VG901 in Patients With Retinitis Pigmentosa Due to Mutations in the CNGA1 Gene Phase 1
Recruiting NCT05909488 - Role of UC-MSC and CM to Inhibit Vision Loss in Retinitis Pigmentosa Phase I/II Phase 2/Phase 3
Recruiting NCT03078309 - The Effects of Cannabis on Visual Functions in Healthy and Retinitis Pigmentosa Patients Early Phase 1
Completed NCT04238858 - Effects of Subtenon-injected Autologous Platelet-rich Plasma on Visual Functions in Eyes With Retinitis Pigmentosa N/A
Active, not recruiting NCT01680510 - The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil Phase 1/Phase 2