Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03780257
Other study ID # PQ-421a-001
Secondary ID 2018-002433-38
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date March 6, 2019
Est. completion date October 14, 2021

Study information

Verified date April 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 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.


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 24 months. 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. Initial dose cohorts will include subjects randomized to sham-procedure or treatment with QR-421a. Additional subjects may be allocated to treatment with QR-421a in subsequent or initial dose cohorts.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date October 14, 2021
Est. primary completion date October 14, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
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. 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. 4. Impairment of 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 any axis in the treatment eye, and evidence of functioning rods. 5. Willing and able to comply with the protocol, follow study instructions, attend study visits as required and complete all study assessments. 6. Willing and able to provide informed consent for participation prior to performing any study related procedures, and suitable verbal, auditory, written and/or tactile sign language communication as to allow informed consent to be obtained, in the opinion of the Investigator. 7. 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. 8. Reliable perimetry measurements in both eyes, as described in the Imaging Manual and determined by the Investigator. 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. Presence of any significant ocular 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: 1) is not an appropriate candidate for antisense oligonucleotide treatment, 2) has cystoid macular edema (CME) in the treatment eye. 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 treatment 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 the treatment eye. 9. Worse than 6 diopters myopia in the treatment eye. 10. 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 during the course of the study. 11. 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. 12. A history of glaucoma or an IOP greater than 24 mmHg in either eye that is not controlled with medication or surgery at the time of informed consent. 13. 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 PQ-421a-001 study period. 14. Any prior treatment with genetic or stem-cell therapy for ocular or non-ocular disease. 15. 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. 16. Known hypersensitivity to antisense oligonucleotides or any constituents of the injection. 17. Pregnant and breastfeeding subjects. Females of childbearing potential and males must comply with using highly effective methods of contraception as defined in Section 6.2.2. Women of non-childbearing potential may be included without the use of adequate birth control, provided they meet the criteria in the protocol.

Study Design


Intervention

Drug:
QR-421a
RNA antisense oligonucleotide for intravitreal injection
Other:
Sham-procedure (dose cohort 1&2 only)
Sham-procedure (no experimental drug administered)

Locations

Country Name City State
Canada Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre Montréal
France Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique Montpellier
France Centre de maladies rares CHNO des Quinze Vingts Paris
United States University of Michigan, Kellogg Eye Center Ann Arbor Michigan
United States Center for Clinical Research Operations, Massachusetts Eye and Ear Boston Massachusetts
United States Retina Foundation of the Southwest Dallas Texas
United States Casey Eye Institute, Oregon Health & Science University Portland Oregon

Sponsors (1)

Lead Sponsor Collaborator
ProQR Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence and severity of ocular adverse events (AEs) in the treatment and contralateral eye Incidence and severity of ocular AEs 24 months
Primary Incidence and severity of non-ocular AEs Incidence and severity of non-ocular AEs 24 months
Secondary Change in DAC perimetry Change in Dark Adapted Chromatic (DAC) perimetry 24 months
Secondary Change in static perimetry Change in static perimetry 24 months
Secondary Change in EZ area by SD-OCT Change in Ellipsoid Zone (EZ) area/width by spectral domain optical coherence tomography (SD-OCT) 24 months
Secondary Change in BCVA Change in Best Corrected Visual Acuity (BCVA) 24 months
Secondary Change in LLVA Change in Low Luminance Visual Acuity (LLVA) 24 months
Secondary Change in microperimetry Change in microperimetry 24 months
Secondary Changes in FST Changes in Full-field Stimulus Threshold (FST) 24 months
Secondary Changes in FAF Changes in Fundus autofluorescence (FAF) 24 months
Secondary AUC (0-8) of QR-421a in serum Area under the curve 0 hour to infinity [AUC(0-8)] of QR-421a in serum 24 months
Secondary AUC (0-tlast) of QR-421a in serum Area under the curve 0 hour to the final sample with a concentration greater than lower limit of quantification (LLOQ) [AUC(0-tlast)] of QR-421a in serum 24 months
Secondary Cmax of QR-421a in serum Maximum concentration (Cmax) of QR-421a in serum 24 months
Secondary Tmax of QR-421a Time to maximum concentration (Tmax) of QR-421a 24 months
Secondary T1/2 of QR-421a Terminal elimination half-life (T1/2) of QR-421a 24 months
Secondary Serum clearance (CL) of QR-421a Serum clearance (CL) of QR-421a 24 months
Secondary Volume of distribution (Vd) of QR-421a Volume of distribution (Vd) of QR-421a 24 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