Fuchs Endothelial Corneal DystrophyPhase 1Fuchs FocusNCT05052554
Study With QR-504a to Evaluate Safety, Tolerability & Corneal Endothelium Molecular Biomarker(s) in Subjects With FECD3
A Phase 1 study testing QR-504a in people with Fuchs Endothelial Corneal Dystrophy and FECD3, run by ProQR Therapeutics at 1 site in United Kingdom.
Trial summary
PQ-504a-001 (Fuchs Focus) is an open-label, single-dose, exploratory study to evaluate safety, tolerability, and corneal endothelium molecular biomarker(s) in subjects with Fuchs Endothelial Corneal Dystrophy with Trinucleotide Repeat Expansion in the TCF4 gene (FECD3). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fuchs Endothelial Corneal Dystrophy, FECD3, Corneal Diseases
- What is being tested?
- QR-504a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Aug 2021to 12 Apr 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- Clinical diagnosis of FECD3 with:
- confirmed presence of trinucleotide repeat (TNR) expansion in the TCF4 gene (50 TNRs or more as determined by PCR),
- symmetrical disease progression in both eyes, in the opinion of the Investigator,
- a clinical indication for DMEK in both eyes ((phakic, aphakic, pseudophakic), or a clinical indication for concurrent, preemptive lens replacement surgery \& DMEK in phakic eye.
Who cannot join
- Presence of any significant ocular or non-ocular disease/disorder which 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.
- History of any form of keratoplasty in either eye.
- History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in either eye.
- Presence of any active ocular infection in either eye.
- Receipt within 3 months prior to Screening of in the opinion of the investigator any procedures or drugs that cause ocular disease or have ocular side effects that may confound assessment of safety, local tolerability or potential efficacy including.
- Systemic therapies known to influence the immune system (including but not limited to cytostatics, interferons, 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 (eg, in pulmonological, dermatological or ophthalmological indications) may be considered for inclusion following approval by the Medical Monitor.
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- Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the study period.
- Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.
- Ongoing event of intraocular tumors.
- Pregnant or breastfeeding subjects. Female subjects of childbearing potential and male subjects must be sexually inactive by abstinence, which is consistent with the preferred and usual lifestyle of the subject, or agree to use highly effective methods of birth control, as defined in the study protocol. Women of non-childbearing potential may be included without the use of adequate birth control, provided the participant meets the criteria.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Moorfields Eye Hospital, NIHR Clinical Research Facility
London
About this study
Official title: Open-Label, Single-Dose, Exploratory Study With QR-504a to Evaluate Safety, Tolerability, and Corneal Endothelium Molecular Biomarker(s) in Subjects With Fuchs Endothelial Corneal Dystrophy With Trinucleotide Repeat Expansion in the TCF4 Gene (FECD3)
PQ-504a-001 (Fuchs Focus) is an open-label, single-dose, exploratory study to evaluate safety, tolerability, and corneal endothelium molecular biomarker(s) in subjects with Fuchs Endothelial Corneal Dystrophy with Trinucleotide Repeat Expansion in the TCF4 gene (FECD3).
Read the detailed description
PQ-504a-001 (Fuchs Focus) is an open-label, intra-subject-controlled study in subjects with FECD3 scheduled for Descemet's Membrane Endothelial Keratoplasty (DMEK) in both eyes or with concurrent, preemptive lens replacement surgery (LRS/DMEK), if indicated as part of routine clinical practice. Each subject will go through the following two parts in this study:
- Part A without study drug administration: Part A of the study starts once LRS/DMEK of the first eye (hereafter called Eye 1) has been scheduled and subject eligibility has been confirmed. During the LRS/DMEK of Eye 1 corneal endothelium will be collected to assess the levels of selected molecular biomarkers. According to routine clinical practice, subjects will then be monitored for at least 4 weeks and up to approximately 6 months to evaluate recovery of Eye 1 prior to scheduling LRS/DMEK of the second eye (hereafter called Eye 2). The duration of the follow-up period also depends on the availability of cornea transplant material for Eye 2. Data generated during this part will serve as intra-subject control for data generated in Part B.
- Part B with study drug administration: Part B of the study starts once LRS/DMEK in Eye 2 can be scheduled and subject eligibility for Part B has been confirmed. At least 4 weeks prior to the scheduled LRS/DMEK in Eye 2, the subject will receive a single dose of QR-504a administered intravitreally in Eye 2. During the LRS/DMEK in Eye 2 corneal endothelium will be collected for molecular biomarker assessments and subjects will continue to be followed for safety and tolerability for at least 12 months post-surgery (ie, at least 13 months post dosing).
- Conditions
- Fuchs Endothelial Corneal Dystrophy, FECD3, Corneal Diseases, LRS, Descemet's Membrane Disorder
- Being tested
- QR-504a
- Medical subject headings
- Fuchs' Endothelial Dystrophy, Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QR-504aDrug
Intravitreal (IVT) injection
| Study group | Role | What they receive |
|---|---|---|
| 30 µg cohort | Experimental | Open label single dose cohort: Dose level 1 Receives: Drug: QR-504a |
| 60 µg cohort | Experimental | Open label single dose cohort: Dose level 2 Receives: Drug: QR-504a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of ocular and non-ocular adverse events (AEs)
Measured: 20 months
Change from baseline in the isoform levels of MBNL1 and MBNL2 in corneal endothelium
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2021
- Study start10 Aug 2021
- Primary completion12 Apr 2022
- Study completion12 Apr 2022
Why it stopped: No patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fuchs Endothelial Corneal DystrophyStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- QR-504a will be administered per intravitreal (IVT) injection, as a single dose. The starting dose is 30 µg. Guided by the dose (de-)escalation plan, doses in a range of below 30 µg and up to 60 µg may be evaluated following pre-specified criteria for opening additional dose cohorts.
- Masking
- None (open label)
- Enrolment
- 0 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 Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05052554
- Sponsor's protocol ID
- PQ-504a-001
- Acronym
- Fuchs Focus
- Status last verified
- May 2022
- First submitted
- 6 Aug 2021
- Last updated
- 11 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Single-Dose, Exploratory Study With QR-504a to Evaluate Safety, Tolerability, and Corneal Endothelium Molecular Biomarker(s) in Subjects With Fuchs Endothelial Corneal Dystrophy With Trinucleotide Repeat Expansion in the TCF4 Gene (FECD3)
- ClinicalTrials.gov ID
- NCT05052554
- Acronym / sponsor ID
- Fuchs Focus / PQ-504a-001
- Conditions
- Fuchs Endothelial Corneal Dystrophy, FECD3, Corneal Diseases, LRS, Descemet's Membrane Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ProQR TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2021 (actual)
- Primary completion
- 12 Apr 2022 (actual)
- Study completion
- 12 Apr 2022 (actual)
- First posted
- 22 Sep 2021 (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.
PQ-504a-001 (Fuchs Focus) is an open-label, single-dose, exploratory study to evaluate safety, tolerability, and corneal endothelium molecular biomarker(s) in subjects with Fuchs Endothelial Corneal Dystrophy with Trinucleotide Repeat Expansion in the TCF4 gene (FECD3).
Detailed description
PQ-504a-001 (Fuchs Focus) is an open-label, intra-subject-controlled study in subjects with FECD3 scheduled for Descemet's Membrane Endothelial Keratoplasty (DMEK) in both eyes or with concurrent, preemptive lens replacement surgery (LRS/DMEK), if indicated as part of routine clinical practice. Each subject will go through the following two parts in this study:
- Part A without study drug administration: Part A of the study starts once LRS/DMEK of the first eye (hereafter called Eye 1) has been scheduled and subject eligibility has been confirmed. During the LRS/DMEK of Eye 1 corneal endothelium will be collected to assess the levels of selected molecular biomarkers. According to routine clinical practice, subjects will then be monitored for at least 4 weeks and up to approximately 6 months to evaluate recovery of Eye 1 prior to scheduling LRS/DMEK of the second eye (hereafter called Eye 2). The duration of the follow-up period also depends on the availability of cornea transplant material for Eye 2. Data generated during this part will serve as intra-subject control for data generated in Part B.
- Part B with study drug administration: Part B of the study starts once LRS/DMEK in Eye 2 can be scheduled and subject eligibility for Part B has been confirmed. At least 4 weeks prior to the scheduled LRS/DMEK in Eye 2, the subject will receive a single dose of QR-504a administered intravitreally in Eye 2. During the LRS/DMEK in Eye 2 corneal endothelium will be collected for molecular biomarker assessments and subjects will continue to be followed for safety and tolerability for at least 12 months post-surgery (ie, at least 13 months post dosing).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- QR-504a will be administered per intravitreal (IVT) injection, as a single dose. The starting dose is 30 µg. Guided by the dose (de-)escalation plan, doses in a range of below 30 µg and up to 60 µg may be evaluated following pre-specified criteria for opening additional dose cohorts.
| Arm | Type | Receives |
|---|---|---|
| 30 µg cohort | Experimental | Drug: QR-504aOpen label single dose cohort: Dose level 1 |
| 60 µg cohort | Experimental | Drug: QR-504aOpen label single dose cohort: Dose level 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical diagnosis of FECD3 with:
- confirmed presence of trinucleotide repeat (TNR) expansion in the TCF4 gene (50 TNRs or more as determined by PCR),
- symmetrical disease progression in both eyes, in the opinion of the Investigator,
- a clinical indication for DMEK in both eyes ((phakic, aphakic, pseudophakic), or a clinical indication for concurrent, preemptive lens replacement surgery \& DMEK in phakic eye.
Key exclusion criteria (10 listed)
- Presence of any significant ocular or non-ocular disease/disorder which 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.
- History of any form of keratoplasty in either eye.
- History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in either eye.
- Presence of any active ocular infection in either eye.
- Receipt within 3 months prior to Screening of in the opinion of the investigator any procedures or drugs that cause ocular disease or have ocular side effects that may confound assessment of safety, local tolerability or potential efficacy including.
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-504aIntravitreal (IVT) injection | Drug | 30 µg cohort, 60 µg cohort |
Primary outcome
Incidence and severity of ocular and non-ocular adverse events (AEs)
Time frame: 20 months
Change from baseline in the isoform levels of MBNL1 and MBNL2 in corneal endothelium
Time frame: 20 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing QR-504a in people with Fuchs Endothelial Corneal Dystrophy and FECD3, run by ProQR Therapeutics at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 11 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 1 site in United Kingdom. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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 and non-ocular adverse events (AEs) (time frame: 20 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 11 May 2022.