AzTrials
AzTrials

Retinitis PigmentosaPhase 1/2StellarNCT03780257

Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene

A Phase 1/2 study testing QR-421a in people with Retinitis Pigmentosa and Usher Syndrome Type 2, run by ProQR Therapeutics at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the 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. Read more about this study

Who is it for?
Ages 18 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
20 participants
Where
7 sitesin 3 countries
Study dates
6 Mar 2019to 14 Oct 2021
Phase
Phase 1/2
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

  • Male or female, ≥ 18 years of age.
  • Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic 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 upon Sponsor approval.
  • Impairment of 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 any axis in the treatment eye, and evidence of functioning rods.
  • Willing and able to comply with the protocol, follow study instructions, attend study visits as required and complete all study assessments.
  • Willing and able to provide informed consent for participation prior to performing any study related procedures, and suitable verbal, auditory, written and/or tactile sign language communication as to allow informed consent to be obtained, in the opinion of the Investigator.
Show all 9Show fewer
  • 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 perimetry measurements in both eyes, as described in the Imaging Manual and determined by the Investigator.
  • Clear ocular media 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 are compound heterozygous for mutations in exon 13.
  • Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who are homozygous for mutations in exon 13.
  • 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.
  • 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: 1) is not an appropriate candidate for antisense oligonucleotide treatment, 2) has cystoid macular edema (CME) in the treatment 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.
Show all 17Show fewer
  • Presence of any of the following lens opacities in the treatment 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 treatment eye.
  • Worse than 6 diopters myopia in the treatment eye.
  • Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection 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 at the time of informed consent.
  • 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 PQ-421a-001 study period.
  • Any prior treatment with genetic or stem-cell therapy for ocular or non-ocular disease.
  • History of malignancy within 5 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 Section 6.2.2. Women of non-childbearing potential may be included without the use of adequate birth control, provided they meet the criteria in the protocol.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

United States4 sites

  • University of Michigan, Kellogg Eye Center

    Ann Arbor, Michigan, 48105

  • Center for Clinical Research Operations, Massachusetts Eye and Ear

    Boston, Massachusetts, 02114

  • Retina Foundation of the Southwest

    Dallas, Texas, 75231

  • Casey Eye Institute, Oregon Health & Science University

    Portland, Oregon, 97239

Other trials in United States

France2 sites

  • Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique

    Montpellier, 34295

  • Centre de maladies rares CHNO des Quinze Vingts

    Paris, 75012

Other trials in France

Canada1 site

  • Centre for Innovative Medicine, Department of Paediatric Surgery, Montreal Children's Hospital at the McGill University Health Centre

    Montreal, H4A 3J1

Other trials in Canada

About this study

Official title: A First-in-Human Study to Evaluate the Safety and Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene

The purpose of this study is to evaluate the 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.

Read the detailed description

The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via IVT in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects will receive one single IVT injection of QR-421a or sham-procedure in one eye (subject's worse eye) and will be followed up for 24 months.

Three dose levels of QR-421a will be evaluated: 50, 100, and 200 µg. Additional dose levels (eg, 25 or 400 µg) may be evaluated based on ongoing safety and efficacy data monitoring.

Initial dose cohorts will include subjects randomized to sham-procedure or treatment with QR-421a. Additional subjects may be allocated to treatment with QR-421a in subsequent or initial dose cohorts.

Being tested
QR-421a, Sham-procedure (dose cohort 1&2 only)
Keywords
Retinitis Pigmentosa, USH2A, RP, exon 13, RNA therapies, antisense oligonucleotide, exon skipping, STELLAR, IVT, mutations in exon 13 of the USH2A gene, NSRP
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-procedure (dose cohort 1&2 only)Other

    Also called Sham-procedure

    Sham-procedure (no experimental drug administered)

Study groups in NCT03780257
Study groupRoleWhat they receive
QR-421aExperimentalSingle dose administration
Receives: Drug: QR-421a
Sham-procedure (dose cohort 1&2 only)Sham comparatorSham-procedure (no experimental drug administered)
Receives: Other: Sham-procedure (dose cohort 1&2 only)

What is being measured

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

  1. Incidence and severity of ocular adverse events (AEs) in the treatment and contralateral eye

    Incidence and severity of ocular AEs

    Measured: 24 months

  2. Incidence and severity of non-ocular AEs

    Incidence and severity of non-ocular AEs

    Measured: 24 months

Secondary outcomes (15)

  1. Change in DAC perimetry

    Change in Dark Adapted Chromatic (DAC) perimetry

    Measured: 24 months

  2. Change in static perimetry

    Change in static perimetry

    Measured: 24 months

  3. Change in EZ area by SD-OCT

    Change in Ellipsoid Zone (EZ) area/width by spectral domain optical coherence tomography (SD-OCT)

    Measured: 24 months

  4. Change in BCVA

    Change in Best Corrected Visual Acuity (BCVA)

    Measured: 24 months

  5. Change in LLVA

    Change in Low Luminance Visual Acuity (LLVA)

    Measured: 24 months

  6. Change in microperimetry

    Change in microperimetry

    Measured: 24 months

  7. Changes in FST

    Changes in Full-field Stimulus Threshold (FST)

    Measured: 24 months

  8. Changes in FAF

    Changes in Fundus autofluorescence (FAF)

    Measured: 24 months

  9. AUC (0-∞) of QR-421a in serum

    Area under the curve 0 hour to infinity [AUC(0-∞)] of QR-421a in serum

    Measured: 24 months

  10. AUC (0-tlast) of QR-421a in serum

    Area under the curve 0 hour to the final sample with a concentration greater than lower limit of quantification (LLOQ) [AUC(0-tlast)] of QR-421a in serum

    Measured: 24 months

  11. Cmax of QR-421a in serum

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

    Measured: 24 months

  12. Tmax of QR-421a

    Time to maximum concentration (Tmax) of QR-421a

    Measured: 24 months

  13. T1/2 of QR-421a

    Terminal elimination half-life (T1/2) of QR-421a

    Measured: 24 months

  14. Serum clearance (CL) of QR-421a

    Serum clearance (CL) of QR-421a

    Measured: 24 months

  15. Volume of distribution (Vd) of QR-421a

    Volume of distribution (Vd) of QR-421a

    Measured: 24 months

Timeline

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

  1. First posted19 Dec 2018
  2. Study start6 Mar 2019
  3. Primary completion14 Oct 2021
  4. Study completion14 Oct 2021

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03780257
Sponsor's protocol ID
PQ-421a-001
Other IDs
2018-002433-38, 2018
Acronym
Stellar
Status last verified
Apr 2022
First submitted
17 Dec 2018
Last updated
20 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chan CM, Tan TE, Jain K, Bylstra Y, Mathur RS, Tang RWC, Lee BJH, Jamuar SS, Kam S, Vithana EN, Lim WK, Fenner BJ. RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations. Retina. 2023 Oct 1;43(10):1788-1796. doi: 10.1097/IAE.0000000000003874.

    PubMed 37418643

  • Miah 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 31215818

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing QR-421a in people with Retinitis Pigmentosa and Usher Syndrome Type 2, run by ProQR Therapeutics at 7 sites in 3 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 9 inclusion and 17 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 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, France, Canada. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 adverse events (AEs) in the treatment and contralateral eye (time frame: 24 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?

On the ClinicalTrials.gov record for NCT03780257, which also lists 2 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 20 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in