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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04123626
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics

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.

Condition or disease Intervention/treatment Phase
Autosomal Dominant Retinitis Pigmentosa Eye Diseases Eye Diseases, Hereditary Retinal Dystrophies Retinal Disease Retinitis Vision Tunnel Vision Disorders Drug: QR-1123 Other: Sham procedure Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
Primary Purpose: Treatment
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
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : October 7, 2021
Estimated Study Completion Date : October 7, 2021


Arm Intervention/treatment
Experimental: QR-1123 Single dose - dose level 1
Open label Single dose cohort: dose level 1
Drug: QR-1123
unilateral IVT injection

Experimental: QR-1123 Single dose - dose level 2
Open label Single dose cohort: dose level
Drug: QR-1123
unilateral IVT injection

Experimental: QR-1123 Single dose - dose level 3
Open label Single dose cohort: dose level 3
Drug: QR-1123
unilateral IVT injection

Experimental: QR-1123 Single dose - dose level 4
Open label Single dose cohort: dose level 4
Drug: QR-1123
unilateral IVT injection

Experimental: Repeat dose cohort 1
Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.
Drug: QR-1123
unilateral IVT injection

Other: Sham procedure
Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment




Primary Outcome Measures :
  1. Incidence and Severity of ocular AEs [ Time Frame: up to 12 months ]
    Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye

  2. Incidence and Severity of non-ocular AEs [ Time Frame: up to 12 months ]
    Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye


Secondary Outcome Measures :
  1. Changes in BCVA [ Time Frame: up to 12 months ]
    Changes in Best corrected visual acuity (BCVA)

  2. Changes in LLVA [ Time Frame: up to 12 months ]
    Changes in Low-luminance visual acuity (LLVA)

  3. Changes in DAC perimetry [ Time Frame: up to 12 months ]
    Changes in Dark adapted chromatic (DAC) perimetry

  4. Changes in Static VF [ Time Frame: up to 12 months ]
    Changes in Static VF (Visual Field)

  5. Changes in Microperimetry [ Time Frame: up to 12 months ]
    Changes in Microperimetry

  6. Changes in SD-OCT [ Time Frame: up to 12 months ]
    Changes in Spectral Domain-Optical Coherence Tomography

  7. Changes in FST [ Time Frame: up to 12 months ]
    Changes in Full-field Stimulus Threshold (FST)

  8. Changes in Full-field ERG [ Time Frame: up to 12 months ]
    Changes in Full-field Electroretinogram (ERG)

  9. Changes in FAF [ Time Frame: up to 12 months ]
    Changes in Fundus Autofluorescence (FAF)

  10. Changes in Contrast sensitivity [ Time Frame: up to 12 months ]
    Changes in Contrast sensitivity

  11. Changes in Color vision [ Time Frame: up to 12 months ]
    Changes in Color vision

  12. Assessment of systemic exposure after treatment with QR-1123 [ Time Frame: up to 12 months ]
    Serum levels of QR-1123



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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's 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123626


Contacts
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Contact: ProQR Clinical Trial Manager +31(0)88 166 7000 clinical@proqr.com

Locations
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United States, Florida
VitreoRetinal Associates Recruiting
Gainesville, Florida, United States, 32607
Contact: Jing Zhang    352-300-8412    Jing@vra-pa.com   
Principal Investigator: C Kay         
United States, Oregon
Casey Eye Institute, OHSU Recruiting
Portland, Oregon, United States, 97239
Contact: Kimberly Voelker    503-494-0020    ordc@ohsu.edu   
Principal Investigator: M Pennesi         
United States, Texas
Retina Foundation of the Southwest Recruiting
Dallas, Texas, United States, 75231
Contact: Tein Luu    214-363-3911 ext 162    tluu@retinafoundation.org   
Principal Investigator: D Birch         
Sponsors and Collaborators
ProQR Therapeutics
Investigators
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Study Director: ProQR Medical Monitor ProQR Therapeutics
Study Director: ProQR Clinical Trial Manager ProQR Therapeutics

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Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT04123626    
Other Study ID Numbers: PQ-1123-001
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ProQR Therapeutics:
adRP
Retinitis Pigmentosa
P23H mutation
Rhodopsin
antisense oligonucleotide
IVT
autosomal dominant
Additional relevant MeSH terms:
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Vision Disorders
Retinitis
Retinitis Pigmentosa
Retinal Diseases
Retinal Dystrophies
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Eye Diseases
Retinal Degeneration
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms