Leber Congenital Amaurosis 10Phase 3HYPERIONNCT06891443
Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
A Phase 3 study testing sepofarsen in people with Leber Congenital Amaurosis 10 and Blindness, run by Laboratoires Thea at 18 sites in 10 countries.
Trial summary
The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is to evaluate the efficacy, safety and tolerability of Sepofarsen in subjects with Leber Congenital Amaurosis (LCA) due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis
- What is being tested?
- sepofarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 18 sitesin 10 countries
- Study dates
- 4 Jun 2025to Oct 2028
- Phase
- Phase 3
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
- Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in CEP290.
- Adults: >=18 years / Minors: 6 to <18 years.
- BCVA (FrACT) equal to or worse than logMAR +0.4 (approximate Snellen equivalent 20/50) to +2.9 logMAR based on quantifiable, reliable FrACT. LP subjects with documented evidence of prior better vision eligible.
- Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline.
- Detectable ONL in the macular area as determined by the CRC at Screening.
Who cannot join
- Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes.
- Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible.
- Presence of unstable concurrent CME, or subject started on (or changed dose of) topical or systemic carbonic anhydrase inhibitor treatment in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment).
- Presence of any clinically significant lens opacities/cataracts based on the AREDS lens grading scale.
- Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
Trial locations and contacts
18 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
Sepul Bio Chief Medical Officer contact
18 sites in 10 countries
United States5 sites, 4 recruiting
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
- Recruiting
University of Miami - Bascom Palmer Eye Institute
Miami, Florida, 33156
- Withdrawn
University of Minnesota Medical School
Minneapolis, Minnesota, 55455
- Recruiting
University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics
Philadelphia, Pennsylvania, 19104
- Recruiting
UCSF Wayne and Gladys Valley Center for Vision
San Francisco, California, 94158
Germany3 sites, 3 recruiting
- Recruiting
Justus-Liebig Universität - Department of Ophthalmology
Giessen, 35392
- Recruiting
Klinikum der Ludwig-Maximilian Universität München
München, 81377
- Recruiting
University of Tuebingen - Inst. for Ophthalmic Research
Tübingen, 72076
Brazil2 sites, 2 recruiting
- Recruiting
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150270
- Recruiting
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
São Paulo, São Paulo, 04023-062
Canada2 sites, 2 recruiting
- Recruiting
University of Alberta
Edmonton, Alberta, T6G 2C8
- Recruiting
The Hospital for Sick Children - SickKids
Toronto, Ontario, M5G 2L3
Australia1 site, 1 recruiting
- Recruiting
Sydney Eye Hospital
Sydney, New South Wales, 2000
Belgium1 site, 1 recruiting
- Recruiting
Universitair Ziekenhuis Gent (UZ)
Ghent, 9000
France1 site, 1 recruiting
- Recruiting
Centre de maladies rares CHNO des Quinze Vingt
Paris, 75012
Netherlands1 site, 1 recruiting
- Recruiting
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA
Spain1 site, 1 recruiting
- Recruiting
Hospital Sant Joan de Déu (SJD Barcelona Children's Hospital)
Barcelona, 08950
United Kingdom1 site, 1 recruiting
- Recruiting
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
About this study
Official title: A Double-Masked, Randomized, Placebo-Controlled, Paired-Eye Study to Evaluate the Efficacy, Safety and Tolerability of Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Due to the c.2991+1655A>G (p.Cys998X) Mutation in the CEP290 Gene
The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is to evaluate the efficacy, safety and tolerability of Sepofarsen in subjects with Leber Congenital Amaurosis (LCA) due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290.
Read the detailed description
This is a double-masked, randomized, placebo-controlled, paired-eye study in which one eye of each subject will serve as a control.
At the start of the study the two eyes of each subject will be randomized such that one eye receives sepofarsen and the other eye receives placebo for the first year. In the second year, for all subjects, the eye that was randomized to receive sepofarsen will continue to receive sepofarsen. For the eye that was randomized to placebo in the first year, treatment in the second year will be allocated, as follows: 50% of the eyes will continue to receive placebo, and 50% of the eyes will receive sepofarsen.
Sepofarsen and placebo will be administered via intravitreal injection every 6 months.
- Conditions
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Sensation Disorders, Vision Disorder, Neurological Manifestations
- Being tested
- sepofarsen, Placebo IVT
- Keywords
- LCA10, p.Cys998X, Antisense oligonucleotides, RNA therapy, QR-110, sepofarsen, CEP290, Leber's Congenital Amaurosis, c.2991+1655A>G
- Medical subject headings
- Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Sensation Disorders, Vision Disorders, Neurologic Manifestations, Eye Diseases, Hereditary, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sepofarsenDrug
Also called QR-110
RNA antisense oligonucleotide for intravitreal injection
Placebo IVTOther
Placebo with identical appearance to sepofarsen
| Study group | Role | What they receive |
|---|---|---|
| Sepofarsen - Treatment Eye - up to Month 12 | Active comparator | Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6. Receives: Drug: sepofarsen |
| Placebo - Fellow Eye - up to Month 12 | Placebo comparator | Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6. Receives: Other: Placebo IVT |
| Continued - Treatment Eye - up to Month 24 | Active comparator | Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18. Receives: Drug: sepofarsen |
| Continued - Fellow Eye - up to Month 24 | Placebo comparator | Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18. Receives: Other: Placebo IVT |
| Mixed - Treatment Eye - up to Month 24 | Active comparator | Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18. Receives: Drug: sepofarsen |
| Mixed - Fellow Eye - Month 12 to Month 24 | Active comparator | Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18. Receives: Drug: sepofarsen |
| Mixed - Fellow Eye - up to Month 12 | Placebo comparator | Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18
Note: up to Month 12 these subjects receive placebo in the Fellow Eye, as all subjects do. Receives: Other: Placebo IVT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Best-Corrected Visual Acuity (BCVA)
Change from baseline in BCVA based on the Freiburg Acuity and Contrast Test (FrACT) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: 12 Months
Secondary outcomes (18)
Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
PGI-C (PATIENT GLOBAL IMPRESSION OF CHANGE ) assesses a patient's perception of overall change in their vision in the respective eye over time. The minimum score (best outcome) is 1 ("Very Much Better") and the maximum score (worst outcome) is 7 ("Very Much Worse"). Higher scores indicate a worse health outcome (greater worsening).
Measured: Month 12
Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: Month 12
Change from baseline in retinal sensitivity as measured by dark-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: Month 12
Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF
Measured: Month 12
Change from baseline in retinal sensitivity as measured by light-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: Month 12
Response in BCVA (FrACT), defined as an improvement of at least 0.2 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response in BCVA (FrACT), defined as an improvement of at least 0.3 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response in Low Luminance Visual Acuity (LLVA) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response in Full-Field Stimulus Test (FST) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response in Patient Global Impression of Change (PGI-C) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response in Contrast Sensitivity (CS) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.
Measured: Month 12
Response defined as a clinically relevant improvement according to a multimodal assessment in TEs compared to the corresponding response in PCEs at 12 months
The multimodal assessment is based on a combination of visual acuity, retinal sensitivity, CS, functional vision, and/or PRO
Measured: Month 12
Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age
Measured: Month 12
Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age
Measured: Month 12
Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age
Measured: Month 12
Change from baseline in eye-specific Patient Global Impression of Severity (PGI-S) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
PGI-S (PATIENT GLOBAL IMPRESSION OF SEVERITY ) assesses a patient's perception of severity of their eye condition in the respective eye over the past week. The minimum score (best outcome) is 1 ("None") and the maximum score (worst outcome) is 5 ("Very Severe"). Higher scores indicate a worse health outcome (greater severity).
Measured: Month 12
Change from baseline in Best-Corrected Visual Acuity (BCVA) based on the ETDRS and/or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: Month 12
Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start4 Jun 2025
- Primary completionNov 2027 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leber Congenital Amaurosis 10Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Paired-eye design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 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
- NCT06891443
- Sponsor's protocol ID
- SB-110-007
- Other IDs
- 2024-518378-14-00
- Acronym
- HYPERION
- Status last verified
- Mar 2026
- First submitted
- 3 Feb 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No