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A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene (AURORA)

Primary Purpose

Autosomal Dominant Retinitis Pigmentosa, Eye Diseases, Eye Diseases, Hereditary

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
QR-1123
Sham procedure
Sponsored by
ProQR Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autosomal Dominant Retinitis Pigmentosa focused on measuring adRP, Retinitis Pigmentosa, P23H mutation, Rhodopsin, antisense oligonucleotide, IVT, autosomal dominant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

  1. Male or female, ≥ 18 years of age.
  2. Clinical presentation consistent with adRP, based on ophthalmic examinations.
  3. Impairment on VF in the opinion of the Investigator, as determined by perimetry.
  4. A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
  5. A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.

Main Exclusion Criteria:

  1. Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc).
  2. Presence of any significant ocular or non-ocular disease/disorder (including medication and 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.

Sites / Locations

  • Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology
  • VitreoRetinal Associates
  • Shriners UK Ophthalmology - University of Kentucky
  • Casey Eye Institute, OHSU
  • Retina Foundation of the Southwest

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

QR-1123 Single dose - dose level 1

QR-1123 Single dose - dose level 2

QR-1123 Single dose - dose level 3

QR-1123 Single dose - dose level 4

QR-1123 Single dose - dose level 5

Repeat dose cohort 1

Arm Description

Open label Single dose cohort: dose level 1

Open label Single dose cohort: dose level

Open label Single dose cohort: dose level 3

Open label Single dose cohort: dose level 4

Open label Single dose cohort: dose level 5

Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.

Outcomes

Primary Outcome Measures

Incidence and Severity of ocular AEs
Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
Incidence and Severity of non-ocular AEs
Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye

Secondary Outcome Measures

Changes in BCVA
Changes in Best corrected visual acuity (BCVA)
Changes in LLVA
Changes in Low-luminance visual acuity (LLVA)
Changes in DAC perimetry
Changes in Dark adapted chromatic (DAC) perimetry
Changes in Static VF
Changes in Static VF (Visual Field)
Changes in Microperimetry
Changes in Microperimetry
Changes in SD-OCT
Changes in Spectral Domain-Optical Coherence Tomography
Changes in FST
Changes in Full-field Stimulus Threshold (FST)
Changes in Full-field ERG
Changes in Full-field Electroretinogram (ERG)
Assessment of systemic exposure after treatment with QR-1123
Serum levels of QR-1123

Full Information

First Posted
October 1, 2019
Last Updated
May 5, 2022
Sponsor
ProQR Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04123626
Brief Title
A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
Acronym
AURORA
Official Title
A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 7, 2019 (Actual)
Primary Completion Date
June 7, 2022 (Anticipated)
Study Completion Date
June 7, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ProQR Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study evaluates the safety, tolerability and efficacy of QR-1123 injection in the eye (intravitreal; IVT) injections (one eye/unilateral) in subjects receiving a single dose or repeat doses. Single injections will be assessed in an open label way, and repeat injections will be assessed in a double-masked, randomized, sham-controlled fashion.
Detailed Description
QR-1123 is an antisense oligonucleotide, designed to specifically target the mutant P23H messenger ribonucleic acid (mRNA) in order to reduce the expression of the P23H protein selectively, while preserving expression of the wild type (WT) rhodopsin (RHO) protein. It is hypothesized that the reduction of mutant P23H mRNA will reduce the deleterious effects of the dominant-negative protein and should result in increased function of WT rhodopsin protein in photoreceptors. Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation. The study will comprise up to 8 single dose and repeat dose cohorts. Prior to initiating a higher single dose cohort and/or prior to initiating repeat dose cohort(s), available safety and efficacy data will be reviewed by the DMC. In the single dose cohorts subjects will receive a single, unilateral IVT injection of QR-1123 in an open label fashion. In the repeat dose cohorts subjects will be randomized to receive either a unilateral IVT injection of QR-1123 every 3 months or a unilateral sham procedure every 3 months, in a double masked fashion. Subjects will be followed for safety, tolerability and efficacy for a total period of 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Retinitis Pigmentosa, Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Disease, Retinitis, Vision Tunnel, Vision Disorders
Keywords
adRP, Retinitis Pigmentosa, P23H mutation, Rhodopsin, antisense oligonucleotide, IVT, autosomal dominant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
QR-1123 Single dose - dose level 1
Arm Type
Experimental
Arm Description
Open label Single dose cohort: dose level 1
Arm Title
QR-1123 Single dose - dose level 2
Arm Type
Experimental
Arm Description
Open label Single dose cohort: dose level
Arm Title
QR-1123 Single dose - dose level 3
Arm Type
Experimental
Arm Description
Open label Single dose cohort: dose level 3
Arm Title
QR-1123 Single dose - dose level 4
Arm Type
Experimental
Arm Description
Open label Single dose cohort: dose level 4
Arm Title
QR-1123 Single dose - dose level 5
Arm Type
Experimental
Arm Description
Open label Single dose cohort: dose level 5
Arm Title
Repeat dose cohort 1
Arm Type
Experimental
Arm Description
Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.
Intervention Type
Drug
Intervention Name(s)
QR-1123
Intervention Description
unilateral IVT injection
Intervention Type
Other
Intervention Name(s)
Sham procedure
Intervention Description
Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment
Primary Outcome Measure Information:
Title
Incidence and Severity of ocular AEs
Description
Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
Time Frame
up to 12 months
Title
Incidence and Severity of non-ocular AEs
Description
Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Changes in BCVA
Description
Changes in Best corrected visual acuity (BCVA)
Time Frame
up to 12 months
Title
Changes in LLVA
Description
Changes in Low-luminance visual acuity (LLVA)
Time Frame
up to 12 months
Title
Changes in DAC perimetry
Description
Changes in Dark adapted chromatic (DAC) perimetry
Time Frame
up to 12 months
Title
Changes in Static VF
Description
Changes in Static VF (Visual Field)
Time Frame
up to 12 months
Title
Changes in Microperimetry
Description
Changes in Microperimetry
Time Frame
up to 12 months
Title
Changes in SD-OCT
Description
Changes in Spectral Domain-Optical Coherence Tomography
Time Frame
up to 12 months
Title
Changes in FST
Description
Changes in Full-field Stimulus Threshold (FST)
Time Frame
up to 12 months
Title
Changes in Full-field ERG
Description
Changes in Full-field Electroretinogram (ERG)
Time Frame
up to 12 months
Title
Assessment of systemic exposure after treatment with QR-1123
Description
Serum levels of QR-1123
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Male or female, ≥ 18 years of age. Clinical presentation consistent with adRP, based on ophthalmic examinations. Impairment on VF in the opinion of the Investigator, as determined by perimetry. A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis. A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator. Main Exclusion Criteria: Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc). Presence of any significant ocular or non-ocular disease/disorder (including medication and 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ProQR Medical Monitor
Organizational Affiliation
ProQR Therapeutics
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
ProQR Clinical Trial Manager
Organizational Affiliation
ProQR Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
VitreoRetinal Associates
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Shriners UK Ophthalmology - University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Casey Eye Institute, OHSU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Retina Foundation of the Southwest
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene

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