Autosomal Dominant Retinitis PigmentosaPhase 1/2AURORANCT04123626
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
A Phase 1/2 study testing QR-1123 in people with Autosomal Dominant Retinitis Pigmentosa and Eye Diseases, run by ProQR Therapeutics at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autosomal Dominant Retinitis Pigmentosa, Eye Diseases, Eye Diseases, Hereditary
- What is being tested?
- QR-1123
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 5 sitesUnited States
- Study dates
- 7 Oct 2019to 7 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology
Aurora, Colorado, 80045
Retina Foundation of the Southwest
Dallas, Texas, 75231
VitreoRetinal Associates
Gainesville, Florida, 32607
Shriners UK Ophthalmology - University of Kentucky
Lexington, Kentucky, 40536
Casey Eye Institute, OHSU
Portland, Oregon, 97239
About this study
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
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.
Read the 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.
- Conditions
- Autosomal Dominant Retinitis Pigmentosa, Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Disease, Retinitis
- Being tested
- QR-1123, Sham procedure
- Keywords
- adRP, Retinitis Pigmentosa, P23H mutation, Rhodopsin, antisense oligonucleotide, IVT, autosomal dominant
- Medical subject headings
- Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Diseases, Retinitis, Vision Disorders, Retinitis Pigmentosa, Night Blindness, Congenital Stationary, Autosomal Dominant 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QR-1123Drug
unilateral IVT injection
Sham procedureOther
Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment
| Study group | Role | What they receive |
|---|---|---|
| QR-1123 Single dose - dose level 1 | Experimental | Open label Single dose cohort: dose level 1 Receives: Drug: QR-1123 |
| QR-1123 Single dose - dose level 2 | Experimental | Open label Single dose cohort: dose level Receives: Drug: QR-1123 |
| QR-1123 Single dose - dose level 3 | Experimental | Open label Single dose cohort: dose level 3 Receives: Drug: QR-1123 |
| QR-1123 Single dose - dose level 4 | Experimental | Open label Single dose cohort: dose level 4 Receives: Drug: QR-1123 |
| QR-1123 Single dose - dose level 5 | Experimental | Open label Single dose cohort: dose level 5 Receives: Drug: QR-1123 |
| Repeat dose cohort 1 | Experimental | Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data. Receives: Drug: QR-1123; Other: Sham procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of ocular AEs
Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
Measured: up to 12 months
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
Measured: up to 12 months
Secondary outcomes (9)
Changes in BCVA
Changes in Best corrected visual acuity (BCVA)
Measured: up to 12 months
Changes in LLVA
Changes in Low-luminance visual acuity (LLVA)
Measured: up to 12 months
Changes in DAC perimetry
Changes in Dark adapted chromatic (DAC) perimetry
Measured: up to 12 months
Changes in Static VF
Changes in Static VF (Visual Field)
Measured: up to 12 months
Changes in Microperimetry
Changes in Microperimetry
Measured: up to 12 months
Changes in SD-OCT
Changes in Spectral Domain-Optical Coherence Tomography
Measured: up to 12 months
Changes in FST
Changes in Full-field Stimulus Threshold (FST)
Measured: up to 12 months
Changes in Full-field ERG
Changes in Full-field Electroretinogram (ERG)
Measured: up to 12 months
Assessment of systemic exposure after treatment with QR-1123
Serum levels of QR-1123
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2019
- Study start7 Oct 2019
- Primary completion7 Jun 2022 (estimated)
- Study completion7 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autosomal Dominant Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- ProQR Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ProQR Medical Monitor, Study director, ProQR TherapeuticsProQR Clinical Trial Manager, Study director, ProQR Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04123626
- Sponsor's protocol ID
- PQ-1123-001
- Acronym
- AURORA
- Status last verified
- May 2022
- First submitted
- 1 Oct 2019
- Last updated
- 6 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04123626
- Acronym / sponsor ID
- AURORA / PQ-1123-001
- Conditions
- Autosomal Dominant Retinitis Pigmentosa, Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Disease, Retinitis
- Keywords
- adRP, Retinitis Pigmentosa, P23H mutation, Rhodopsin, antisense oligonucleotide, IVT, autosomal dominant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 11 participants (actual)
- Lead sponsor
- ProQR TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 7 Oct 2019 (actual)
- Primary completion
- 7 Jun 2022 (estimated)
- Study completion
- 7 Jun 2022 (estimated)
- First posted
- 11 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| QR-1123 Single dose - dose level 1 | Experimental | Drug: QR-1123Open label Single dose cohort: dose level 1 |
| QR-1123 Single dose - dose level 2 | Experimental | Drug: QR-1123Open label Single dose cohort: dose level |
| QR-1123 Single dose - dose level 3 | Experimental | Drug: QR-1123Open label Single dose cohort: dose level 3 |
| QR-1123 Single dose - dose level 4 | Experimental | Drug: QR-1123Open label Single dose cohort: dose level 4 |
| QR-1123 Single dose - dose level 5 | Experimental | Drug: QR-1123Open label Single dose cohort: dose level 5 |
| Repeat dose cohort 1 | Experimental | Drug: QR-1123, Other: Sham procedureDouble-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QR-1123unilateral IVT injection | Drug | 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 |
| Sham procedureSham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment | Other | Repeat dose cohort 1 |
Primary outcome
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
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
9 secondary outcomes
Changes in BCVA
Time frame: up to 12 months
Changes in LLVA
Time frame: up to 12 months
Changes in DAC perimetry
Time frame: up to 12 months
Changes in Static VF
Time frame: up to 12 months
Changes in Microperimetry
Time frame: up to 12 months
Changes in SD-OCT
Time frame: up to 12 months
Changes in FST
Time frame: up to 12 months
Changes in Full-field ERG
Time frame: up to 12 months
Assessment of systemic exposure after treatment with QR-1123
Time frame: up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ProQR Medical Monitor study director
ProQR Therapeutics
ProQR Clinical Trial Manager study director
ProQR Therapeutics
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing QR-1123 in people with Autosomal Dominant Retinitis Pigmentosa and Eye Diseases, run by ProQR Therapeutics at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of ocular AEs (time frame: up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2022.