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Retinitis PigmentosaPhase 2/3NCT05176717

Study to Evaluate the Efficacy Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene With Early to Moderate Vision Loss (Celeste)

A Phase 2/3 study testing QR-421a in people with Retinitis Pigmentosa and Usher Syndrome Type 2, run by Laboratoires Thea at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene with early to moderate vision loss. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
QR-421a
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5 participants
Where
3 sitesin 2 countries
Study dates
15 Dec 2021to 2 Aug 2022
Phase
Phase 2/3
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female, ≥ 18 years of age OR a minor (12 to < 18 years) with permission from a parent or legal guardian.
  • An adult willing to comply with the protocol, follow study instructions, attend study visits as required and willing and able to complete all study assessments. OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions, and attend study visits with the subject as required.
  • Clinical presentation consistent with RP with Usher syndrome type 2 or nonsyndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
  • A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis at screening.
  • BCVA better than ≥69 letters (approximate Snellen equivalent 20/40) in the study eye, using the best BCVA reading at Screening.
  • Impairment of Visual Field (VF) in the opinion of the Investigator as determined by perimetry, with a continuous area of central field greater than or equal to 10 degrees diameter in each meridian as measured by a size V4e target, and a mean defect of ≥ 10 dB, in the study eye.
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  • Clearly visible and measurable ellipsoid zone (EZ) width and/or area on SDOCT, per investigator judgement.
  • No limitations to SD-OCT image collection that would prevent high quality, reliable images from being obtained in both eyes, as determined by the Investigator.
  • Reliable Best Corrected Visual Acuity (BCVA), perimetry, and other measurements in both eyes, as described in the Study Reference Manual and Imaging Manual and determined by the Investigator.
  • No visually significant ocular media opacities and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.

Who cannot join

  • Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who have monoallelic exon-13 mutations.
  • Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations.
  • Presence of pathogenic mutations in genes (other than the USH2A gene) associated with Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or syndromes. Note: The confirmed presence of homozygous or compound heterozygous known disease-causing mutations in other genes involved in recessive retinal dystrophies (RD), or the confirmed presence of known disease-causing mutations in genes involved in dominant or X-linked retinal dystrophies is exclusionary.
  • Presence of any significant ocular or non-ocular disease/disorder (or medication and/or 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. This includes but is not limited to a subject who has uncontrolled cystoid macular edema (CME) in the study eye. CME is permissible if stable for 3 months (with or without treatment). Past CME is permissible if resolved for more than 1 month.
  • 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.
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  • Presence of any of the following lens opacities in the study eye: cortical opacity ≥ +2, posterior subcapsular opacity ≥ +2, or a nuclear sclerosis ≥ +2, and which are: 1) clinically significant in the opinion of the Investigator, 2) would adequately prevent clinical and photographic evaluation of the retina.
  • History of amblyopia in the study eye that resulted in significant vision loss, in the opinion of the Investigator.
  • Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection other or planned intraocular surgery or procedure during the course of the study.
  • Current treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to steroid implants, cytostatics, interferons, tumor necrosis factor (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 may be considered for inclusion following approval by the Medical Monitor.
  • A history of glaucoma or an IOP greater than 24 mmHg in either eye that is not controlled with medication or surgery.
  • Use of any investigational drug or device within 90 days or 5 half-lives preceding the first dose of study medication, whichever is longer, or plans to participate in another study of an investigational drug or device during the course of the study.
  • Any prior treatment with genetic or stem-cell therapy for ocular or non-ocular disease.
  • History of malignancy within 2 years prior to Screening, except adequately treated squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
  • Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
  • Pregnant and breastfeeding subjects. Females of childbearing potential and males must comply with using highly effective methods of contraception as defined in the protocol. Women of non-childbearing potential may be included without the use of adequate birth control.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Retina Foundation of the Southwest

    Dallas, Texas, 75231

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53705

Other trials in United States

United Kingdom1 site

  • Moorfields Eye Hospital

    London

Other trials in United Kingdom

About this study

Official title: A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety and Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene With Early to Moderate Vision Loss

The purpose of this study is to evaluate the efficacy safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene with early to moderate vision loss.

Read the detailed description

The purpose of this study is to evaluate the efficacy safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene with early to moderate vision loss.

The below dose levels of QR-421a will be evaluated with the loading dose administered at Day 1 and maintenance dose administered at Month 3 and every 6 months thereafter:

  1. Loading dose of 180 μg, maintenance dose of 60 μg
  2. Loading dose of 60 μg, maintenance dose of 60 μg

Dose levels will include subjects randomized to sham-procedure or treatment with QR-421a. After the study eye has been treated for at least 12 months, treatment of the fellow eye and cross-over of subjects assigned to sham-procedure may be initiated in eligible eyes based on assessment of benefit-risk.

Being tested
QR-421a, Sham-procedure
Keywords
Retinitis Pigmentosa, USH2A, RP, exon 13, RNA therapies, antisense oligonucleotide, exon skipping, Celeste, IVT, mutations in exon 13 of the USH2A gene, NSRP, Intravitreal Injection, Non-Syndromic RP, Inherited Retinal Diseases, Usher Syndrome
Medical subject headings
Retinitis Pigmentosa, Usher Syndromes, Retinal Diseases, Eye Diseases, Eye Diseases, Hereditary, Eye Abnormalities, Vision Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • QR-421aDrug

    Also called RNA antisense oligonucleotide for intravitreal injection

    RNA antisense oligonucleotide for intravitreal injection

  • Sham-procedureOther

    Sham-procedure (no experimental drug administered)

Study groups in NCT05176717
Study groupRoleWhat they receive
QR-421a 180/60 µgExperimental180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter
Receives: Drug: QR-421a
QR-421a 60/60 µgExperimental60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter
Receives: Drug: QR-421a
Sham-procedureSham comparatorSham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter
Receives: Other: Sham-procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Mean Sensitivity

    Change from baseline in mean sensitivity (based on static perimetry) at 12 months of treatment versus sham-procedure

    Measured: 12 months

Secondary outcomes (11)

  1. Ellipzoid Zone Area (EZ) as Measured by Spectral Domain Optical Coherence Tomography SD-OCT

    Ellipzoid Zone area (EZ) as measured by Spectral Domain optical coherence tomography SD-OCT

    Measured: 27 months

  2. Change From Baseline in Best Corrected Visual Acuity (BCVA)

    Change from baseline in Best Corrected Visual Acuity (BCVA)

    Measured: 27 months

  3. Change From Baseline in Spectral Domain Optical Coherence Tomography (SD-OCT) (Other Measures)

    Change from baseline in Spectral domain optical coherence tomography (SD-OCT) (other measures)

    Measured: 27 months

  4. Change From Baseline in Low Luminance Visual Acuity (LLVA)

    Change from baseline in Low Luminance Visual Acuity (LLVA) using the ETDRS vision chart

    Measured: 27 months

  5. Change From Baseline in Other Measures of Static Perimetry

    Change from baseline in other measures of static perimetry on the Octopus 900 as assessed by a central reading center

    Measured: 27 months

  6. Change From Baseline in Full-field Stimulus Threshold (FST)

    Change from baseline in Full-field Stimulus Threshold (FST) on the Diagnosys FST as assessed by a central reading center

    Measured: 27 months

  7. Change From Baseline in PRO Measure as Assessed by Michigan Retinal Degeneration Questionnaire (MRDQ)

    Change from baseline in PRO measure as assessed by Michigan Retinal Degeneration Questionnaire (MRDQ)

    Measured: 27 months

  8. Change From Baseline in PRO Measures as Assessed by Patient Global Impressions of Severity (PGI-S)

    Change from baseline in PRO measures as assessed by Patient Global Impressions of Severity (PGI-S)

    Measured: 27 months

  9. Change From Baseline in PRO Measures as Assessed by Patient Global Impressions of Change (PGI-C)

    Change from baseline in PRO measures as assessed by Patient Global Impressions of Change (PGI-C)

    Measured: 27 months

  10. Ocular and Non-ocular Adverse Events (AEs)

    Ocular and non-ocular adverse events (AEs)

    Measured: 27 months

  11. Cmax of QR-421a in Serum

    Maximum concentration (Cmax) of QR-421a in serum

    Measured: 27 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2022
  2. Study start15 Dec 2021
  3. Primary completion2 Aug 2022
  4. Study completion2 Aug 2022

Why it stopped: Business decision

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
After primary endpoint is assessed at 12 months, subjects continue the same randomized treatment in the fellow eye. Subjects enrolled to sham treatment will be randomized to receive one of the two ultevursen doses in a parallel design fashion. Double-masked, randomized, controlled, multiple-dose study. Subjects will be randomized to one of three treatment groups: 1. Group 1: QR-421a 180/60 µg (180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter) 2. Group 2: QR-421a 60/60 µg (60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter; n = 27) 3. Group 3: Sham-procedure (administered on Day 1, Month 3 and every 6 months thereafter; n = 27)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05176717
Sponsor's protocol ID
PQ-421a-004
Other IDs
2021-002728-19
Status last verified
Jul 2024
First submitted
23 Nov 2021
Last updated
7 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing QR-421a in people with Retinitis Pigmentosa and Usher Syndrome Type 2, 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 10 inclusion and 16 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: stopped early, as of the sponsor's last update on 7 Aug 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, 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 20 Jan 2023). 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?

Change From Baseline in Mean Sensitivity (time frame: 12 months). 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 NCT05176717.

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 7 Aug 2024.

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