Leber's Congenital AmaurosisPhase 1/2NCT03140969
Study to Evaluate QR-110 in Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
A Phase 1/2 study testing QR-110 in people with Leber's Congenital Amaurosis, run by Laboratoires Thea at 3 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Leber's Congenital Amaurosis
- What is being tested?
- QR-110
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 16 Oct 2017to 2 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, ≥ 6 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation.
- Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye.
- Detectable outer nuclear layer (ONL) in the area of the macula.
- An electroretinogram (ERG) result consistent with LCA.
- Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.
Who cannot join
- Syndromic disease.
- Pregnant or breast-feeding female.
- Any clinically significant cardiac disease or defect.
- One or more coagulation parameters outside of the normal range.
- Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety.
- Prior receipt of intraocular surgery or intravitreal injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study.
- 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 PQ-110-001 study period.
- Any prior receipt of genetic therapy for LCA
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
University of Iowa
Iowa City, Iowa, 52242
Scheie Eye Institute, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.
Read the detailed description
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.
- Conditions
- Leber's Congenital Amaurosis
- Being tested
- QR-110
- Keywords
- CEP290, p.Cys998X, c.2991+1655A>G, RNA therapy, Antisense oligonucleotide, Leber's congenital amaurosis
- Medical subject headings
- Optic Atrophy, Hereditary, Leber, Meckel Syndrome, Type 4
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QR-110Drug
Also called Sepofarsen
RNA antisense oligonucleotide for intravitreal injection
| Study group | Role | What they receive |
|---|---|---|
| QR-110 | Experimental | Administered every 3 months Receives: Drug: QR-110 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes
Measured: 1 year
Secondary outcomes (4)
Frequency and Severity of Non-ocular Adverse Events
Measured: 1 year
Change in Best-corrected Visual Acuity (BCVA)
Measured: 1 year
Change in Full-field Stimulus Test (FST)
Average Red Light Score
Measured: 1 year
Change in Full-field Stimulus Test (FST)
Average Blue Light Score
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start16 Oct 2017
- Primary completion2 Oct 2019
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Leber's Congenital AmaurosisStudies 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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratoires Thea
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sepul Bio
- Responsible party
- Sponsor
- Investigators
- Sepul Bio Chief Medical Officer, Study director, Sepul Bio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03140969
- Sponsor's protocol ID
- PQ-110-001
- Other IDs
- 2017-000813-22, 2017
- Status last verified
- Oct 2024
- First submitted
- 1 May 2017
- Last updated
- 15 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial. Nat Med. 2022 May;28(5):1014-1021. doi: 10.1038/s41591-022-01755-w. Epub 2022 Apr 4.
PubMed 35379979Cideciyan AV, Jacobson SG, Ho AC, Garafalo AV, Roman AJ, Sumaroka A, Krishnan AK, Swider M, Schwartz MR, Girach A. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report. Nat Med. 2021 May;27(5):785-789. doi: 10.1038/s41591-021-01297-7. Epub 2021 Apr 1.
PubMed 33795869Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.
PubMed 31215818Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, Roman AJ, Sumaroka A, Han IC, Hochstedler MD, Pfeifer WL, Sohn EH, Taiel M, Schwartz MR, Biasutto P, Wit W, Cheetham ME, Adamson P, Rodman DM, Platenburg G, Tome MD, Balikova I, Nerinckx F, Zaeytijd J, Van Cauwenbergh C, Leroy BP, Russell SR. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019 Feb;25(2):225-228. doi: 10.1038/s41591-018-0295-0. Epub 2018 Dec 17.
PubMed 30559420
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
- ClinicalTrials.gov ID
- NCT03140969
- Acronym / sponsor ID
- PQ-110-001
- Conditions
- Leber's Congenital Amaurosis
- Keywords
- CEP290, p.Cys998X, c.2991+1655A>G, RNA therapy, Antisense oligonucleotide, Leber's congenital amaurosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Laboratoires TheaIndustry (pharma, biotech, devices)
- Collaborators
- Sepul Bio
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 2 Oct 2019 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Posted 27 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.
Detailed description
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| QR-110 | Experimental | Drug: QR-110Administered every 3 months |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female, ≥ 6 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation.
- Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye.
- Detectable outer nuclear layer (ONL) in the area of the macula.
- An electroretinogram (ERG) result consistent with LCA.
- Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.
Key exclusion criteria (8 listed)
- Syndromic disease.
- Pregnant or breast-feeding female.
- Any clinically significant cardiac disease or defect.
- One or more coagulation parameters outside of the normal range.
- Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety.
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-110Also: SepofarsenRNA antisense oligonucleotide for intravitreal injection | Drug | QR-110 |
Primary outcome
Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes
Time frame: 1 year
4 secondary outcomes
Frequency and Severity of Non-ocular Adverse Events
Time frame: 1 year
Change in Best-corrected Visual Acuity (BCVA)
Time frame: 1 year
Change in Full-field Stimulus Test (FST)
Time frame: 1 year
Change in Full-field Stimulus Test (FST)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35379979Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial. Nat Med. 2022 May;28(5):1014-1021. doi: 10.1038/s41591-022-01755-w. Epub 2022 Apr 4.
- Derived from this study: PubMed 33795869Cideciyan AV, Jacobson SG, Ho AC, Garafalo AV, Roman AJ, Sumaroka A, Krishnan AK, Swider M, Schwartz MR, Girach A. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report. Nat Med. 2021 May;27(5):785-789. doi: 10.1038/s41591-021-01297-7. Epub 2021 Apr 1.
- Derived from this study: PubMed 31215818Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.
- Derived from this study: PubMed 30559420Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, Roman AJ, Sumaroka A, Han IC, Hochstedler MD, Pfeifer WL, Sohn EH, Taiel M, Schwartz MR, Biasutto P, Wit W, Cheetham ME, Adamson P, Rodman DM, Platenburg G, Tome MD, Balikova I, Nerinckx F, Zaeytijd J, Van Cauwenbergh C, Leroy BP, Russell SR. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019 Feb;25(2):225-228. doi: 10.1038/s41591-018-0295-0. Epub 2018 Dec 17.
- 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.
Sepul Bio Chief Medical Officer study director
Sepul Bio
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing QR-110 in people with Leber's Congenital Amaurosis, run by Laboratoires Thea at 3 sites in 2 countries.
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 5 inclusion and 8 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: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Belgium. 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?
Yes. Results are posted in the registry (first posted 27 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Frequency and Severity of Ocular Adverse Events in the Treatment and Contralateral Eyes (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03140969, which also lists 4 linked publications.
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 15 Oct 2024.