Retinitis Pigmentosa (RP)Phase 2LUNANCT06627179
Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
A Phase 2 study testing Intravitreal Injection of Ultevursen in people with Retinitis Pigmentosa (RP) and Usher Syndrome Type 2, run by Laboratoires Thea at 26 sites in 10 countries.
Trial summary
The purpose of this Phase 2b study is to evaluate the safety and tolerability of ultevursen 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 8 years and older
- Conditions the study is for
- Retinitis Pigmentosa (RP), Usher Syndrome Type 2, Deaf Blind
- What is being tested?
- Intravitreal Injection of Ultevursen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 26 sitesin 10 countries
- Study dates
- 11 Dec 2024to Jul 2028
- Phase
- Phase 2
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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- An adult (≥18 years) willing and able to provide informed consent for participation prior to performing any study related procedures
- OR A minor (8 to <18 years) able to provide age-appropriate assent for study participation with a parent or legal guardian willing and able to provide written permission for the subject's participation prior to performing any study related procedures. 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, in the opinion of the Investigator.
- 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, in the opinion of the Investigator.
- Both eyes exhibit clinical presentation consistent with RP involving Usher syndrome type 2 or NSRP based on ophthalmic, audiologic, or vestibular examinations. At screening, the Investigator will make the clinical diagnosis of "Usher syndrome type 2a," defined as RP with congenital hearing loss, or "non-syndromic RP," defined as RP without congenital hearing loss.
- A molecular diagnosis of biallelic disease causing variants (pathogenic or likely pathogenic) in the USH2A gene where at least one of the variants is located on exon 13. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval.
- Clearly visible and measurable SD-OCT horizontal EZ width of ≥2.2 mm in both eyes based on the assessment of the CRC.
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- BCVA ≥55 letters based on ETDRS (equivalent to 20/80 based on Snellen notation, or logarithm of the minimum angle of resolution [logMAR] +0.6) in both eyes.
- Impairment of VF as assessed by SP with a mean sensitivity greater than 4 decibels (dB) and less than 25 dB measured by a V target size in the TE at screening.
- Mean sensitivity greater than 2 dB as determined by MP in the TE at screening.
- Symmetry of baseline disease in both eyes, defined as the mean BCVA (based on ETDRS) of one eye within ≤10 letters of the mean BCVA of the other eye at screening.
Who cannot join
- Presence of additional non-exon 13 USH2A pathogenic or likely pathogenic variant on the USH2A allele carrying the exon 13 mutation in subjects who have one exon 13 disease causing variant and one non-exon 13 disease causing variant.
- Presence of additional non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations.
- Presence of pathogenic or likely pathogenic variants in genes (other than the USH2A gene) which are known to be associated with other inherited retinal degenerative diseases or syndromes. Specifically, the presence of homozygous or compound heterozygous known disease-causing mutations in other genes involved in recessive retinal dystrophies, or the confirmed presence of a known single disease-causing variant in genes involved in dominant, X-linked, or mitochondrial retinal dystrophy genes is exclusionary.
- At screening, the EZ horizontal or vertical width are outside the field of the SD-OCT scan based on the assessment of the CRC.
- Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator may either put the subject at risk because of participation in the study, may impact the subject's ability to participate in the study, or may interfere with assessment of efficacy and safety in the study.
- Presence of unstable concurrent cystoid macular edema (CME), or subject started on (or changed dose of) any medication for CME in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment). However, stable CME that disrupts the EZ width measurement, as determined by CRC, is an exclusion.
- Any intraocular surgery within 3 months of study entry or any planned intraocular or peri-ocular surgery during the study. Subjects may be eligible after 3 months post-surgery as long as they have fully recovered, in the opinion of the Investigator.
- Receipt of any IVT injection prior to study entry.
Trial locations and contacts
26 sites in 10 countries.
26 sites in 10 countries
United States10 sites
University of Michigan- Kellogg Eye Center
Ann Arbor, Michigan, 48105
Emory University
Atlanta, Georgia, 30322
Massachusetts Eye and Ear
Boston, Massachusetts, 02114
Retina Foundation of the Southwest
Dallas, Texas, 75231
Baylor College of Medicine
Houston, Texas, 77030
University of Wisconsin- Madison
Madison, Wisconsin, 53705
Bascom Palmer Eye Institute/University of Miami
Miami, Florida, 33136
University of Pennsylvania, Scheie Eye Institute
Philadelphia, Pennsylvania, 19104
Casey Eye Institute, Oregon Health & Science University
Portland, Oregon, 97239
The University of California, San Francisco
San Francisco, California, 94143
Netherlands3 sites
Amsterdam University Medical Center - Locatie AMC
Amsterdam, 1105 AZ
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA
Het Oogziekenhuis Rotterdam
Rotterdam, 3011 BH
United Kingdom3 sites
University of Edinburgh / NHS Lothian
Edinburgh, EH39HA
Oxford Eye Hospital
Headington, Oxford, OX3 9DU
Moorfields Eye Hosptial
London, EC1V 2PD
Brazil2 sites
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, 30150270
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
São Paulo, 04021-001
Canada2 sites
McGill University Health Centre for Innovative Medicine
Montreal, Quebec, H4A3J1
Hospital for Sick Children
Toronto, Ontario, M5G1E8
France2 sites
Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique
Montpellier, 34295
Centre de maladies rares CHNO des Quinze Vingt
Paris, 75012
Denmark1 site
Rigshospitalet and University of Copenhagen
Glostrup Municipality, 2600
About this study
Official title: A Two-Year Double-masked, Randomized, Sham-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
The purpose of this Phase 2b study is to evaluate the safety and tolerability of ultevursen administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. This is a multicenter Double-masked, Randomized, Sham-controlled study which will enroll 81 subjects.
Read the detailed description
A total of eighty-one (81) RP subjects will be enrolled in this study, randomized in a 2:1 ratio to either ultevursen or sham procedure, respectively. Subjects randomized to the active treatment group will receive therapy with ultevursen administered via intravitreal (IVT) injection to the treatment eye (TE) on Day 1 and at Months 6, 12, and 18. Subjects randomized to sham will undergo a sham procedure in the TE at the corresponding timepoints.
- Conditions
- Retinitis Pigmentosa (RP), Usher Syndrome Type 2, Deaf Blind, Retinal Disease, Eye Diseases, Hereditary, Eye Disorders Congenital
- Being tested
- Intravitreal Injection of Ultevursen, No intervention, will not receive any active study intervention
- Keywords
- Retinitis Pigmentosa, Usher Syndrome Type 2, Deaf Blind, USH2A, RP, Exon 13, RNA therapies, antisense oligonucleotide, exon skipping, LUNA, IVT, NSRP
- Medical subject headings
- Retinitis Pigmentosa, Usher Syndromes, Retinal 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.
Intravitreal Injection of UltevursenDrug
Up to 4 doses over a 24-month period
No intervention, will not receive any active study interventionOther
Sham-procedure (no experimental drug administered)
| Study group | Role | What they receive |
|---|---|---|
| Ultevursen 180/60 μg | Experimental | Subjects will receive an intravitreal injection (IVT) of ultevursen with concentrations of 3.6 mg/mL for initial dose and 1.2 mg/mL for maintenance doses every 6 months thereafter through Month 18 (up to 4 doses). Receives: Drug: Intravitreal Injection of Ultevursen |
| Sham Procedure | Sham comparator | Sham-procedure (no experimental drug administered) Receives: Other: No intervention, will not receive any active study intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate efficacy after 24 months of treatment
Annualized percent change from baseline in ellipsoid zone (EZ) width as measured by spectral-domain optical coherence tomography (SD-OCT) up to Month 24.
Measured: 24 Months
Secondary outcomes (10)
Annualized change from baseline in static perimetry (SP) mean sensitivity
Measured: Month 24
Annualized change from baseline in microperimetry (MP) mean sensitivity
Measured: Month 24
Change from baseline in low luminance visual acuity (LLVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart
Measured: Month 24
Change from baseline in best-corrected visual acuity (BCVA) using the ETDRS chart
Measured: Month 24
Percent change from baseline in EZ area by SD-OCT
Measured: Month 24
Percent change from baseline in EZ width by SD-OCT
Measured: Month 24
Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) for subjects ≥13 years of age
Michigan Retinal Degeneration Questionnaire (MRDQ) scores in central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity Unabbreviated scale title: Michigan Retinal Degeneration Questionnaire Minimum and Maximum values: -3 and +3 Higher scores indicate a worse outcome.
Measured: Month 24
Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) for subjects ≥13 years of age
Michigan Vision-Related Anxiety Questionnaire (MVAQ) scores in rod-function anxiety and cone-function anxiety.
Unabbreviated scale title: Michigan Vision-Related Anxiety Questionnaire Minimum and Maximum values: -3 and +3 Higher scores indicate a worse outcome.
Measured: Month 24
Frequency and severity of ocular and non-ocular adverse events (AEs)
Measured: Up to month 24
Systemic Exposure
Systemic serum concentration of ultevursen
Measured: Up to month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2024
- Study start11 Dec 2024
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Retinitis Pigmentosa (RP)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laboratoires Thea
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sepul Bio
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06627179
- Sponsor's protocol ID
- SB-421a-006
- Other IDs
- 2024-515199-10-00
- Acronym
- LUNA
- Status last verified
- Jul 2025
- First submitted
- 25 Sep 2024
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stephenson KAJ, Dhanji SR, Kolawole OU, Gregory-Evans CY, Gregory-Evans K. Ethnic disparities in inherited retinal degenerations. Can J Ophthalmol. 2025 Dec;60(6):e869-e878. doi: 10.1016/j.jcjo.2025.04.007. Epub 2025 Jun 6.
PubMed 40339601