ClinicalTrials.gg
RecruitingNCT06891443HYPERIONUpdated Oct 21, 2026

Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)

A Phase 3 interventional study of sepofarsen and Placebo IVT in Leber Congenital Amaurosis 10, Blindness and Leber Congenital Amaurosis, sponsored by Laboratoires Thea. Recruiting at 18 sites in 10 countries. Open to participants aged 6 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.

Sponsored by Laboratoires Thea · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Jun 2025; still recruiting 1 year 5 months later.
Updated Oct 21, 2026First site in AustraliaSite recruiting status changed+1 moreGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
32
Allocation
Randomized
Ages
6 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Leber Congenital Amaurosis 10
  • Blindness
  • Leber Congenital Amaurosis
  • Sensation Disorders
  • Vision Disorder
  • Neurological Manifestations
  • Eye Diseases, Hereditary
  • Eye Diseases
  • Eye Disorders Congenital
  • Retinal Disease

Keywords

  • LCA10
  • p.Cys998X
  • Antisense oligonucleotides
  • RNA therapy
  • QR-110
  • sepofarsen
  • CEP290
  • Leber's Congenital Amaurosis
  • c.2991+1655A>G
03

In context

Blindness

144 studies on the registry are indexed under Blindness; 33 are open to participants now.

This study's planned enrollment of 32 is below the median of 37 across 101 interventional studies indexed under Blindness.

Browse Blindness studies →

Lead sponsor

Laboratoires Thea is the lead sponsor of 64 studies on the registry; 6 are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 6 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in CEP290.
  2. Adults: >=18 years / Minors: 6 to \<18 years.
  3. 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.
  4. Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline.
  5. Detectable ONL in the macular area as determined by the CRC at Screening.

Exclusion criteria

Exclusion Criteria:

  1. Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes.
  2. Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible.
  3. 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).
  4. Presence of any lens opacities/cataracts based on the AREDS lens grading scale.
  5. Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
32 participants (estimated)

Study arms

  • Active comparator
    Sepofarsen - Treatment Eye - up to Month 12

    Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.

    Drug: sepofarsen

  • Placebo comparator
    Placebo - Fellow Eye - up to Month 12

    Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.

    Other: Placebo IVT

  • Active comparator
    Continued - Treatment Eye - up to Month 24

    Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

    Drug: sepofarsen

  • Placebo comparator
    Continued - Fellow Eye - up to Month 24

    Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

    Other: Placebo IVT

  • Active comparator
    Mixed - Treatment Eye - up to Month 24

    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.

    Drug: sepofarsen

  • Active comparator
    Mixed - Fellow Eye - Month 12 to Month 24

    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.

    Drug: sepofarsen

  • Placebo comparator
    Mixed - Fellow Eye - up to Month 12

    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.

    Other: Placebo IVT

Interventions

  • RNA antisense oligonucleotide for intravitreal injection

    Also known as: QR-110

  • OtherPlacebo IVT

    Placebo with identical appearance to sepofarsen

06

What researchers measure

Primary outcomes

  1. 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)

    Time frame: 12 Months

Secondary outcomes

  1. 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).

    Time frame: Month 12

  2. Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)

    Time frame: Month 12

  3. 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)

    Time frame: Month 12

  4. Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF

    Time frame: Month 12

  5. 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)

    Time frame: Month 12

  6. 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.

    Time frame: Month 12

  7. 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.

    Time frame: Month 12

  8. 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.

    Time frame: Month 12

  9. 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.

    Time frame: Month 12

  10. 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.

    Time frame: Month 12

  11. 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.

    Time frame: Month 12

  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

    Time frame: Month 12

  13. Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age

    Time frame: Month 12

  14. Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age

    Time frame: Month 12

  15. Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age

    Time frame: Month 12

  16. 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).

    Time frame: Month 12

  17. 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)

    Time frame: Month 12

  18. Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)

    Time frame: Month 12

07

Study locations

17 of 18 sites recruiting
  • UCSF Wayne and Gladys Valley Center for Vision
    San Francisco, California 94158, United States
    Recruiting
  • University of Miami - Bascom Palmer Eye Institute
    Miami, Florida 33156, United States
    Recruiting
  • University of Iowa
    Iowa City, Iowa 52242, United States
    Recruiting
  • University of Minnesota Medical School
    Minneapolis, Minnesota 55455, United States
    Withdrawn

    Not enrolling at this site.

  • University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics
    Philadelphia, Pennsylvania 19104, United States
    Recruiting
  • Sydney Eye Hospital
    Sydney, New South Wales 2000, Australia
    Recruiting
  • Universitair Ziekenhuis Gent (UZ)
    Ghent, 9000, Belgium
    Recruiting
  • INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
    Belo Horizonte, Minas Gerais 30150270, Brazil
    Recruiting
  • Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
    São Paulo, São Paulo 04023-062, Brazil
    Recruiting
  • University of Alberta
    Edmonton, Alberta T6G 2C8, Canada
    Recruiting
  • The Hospital for Sick Children - SickKids
    Toronto, Ontario M5G 2L3, Canada
    Recruiting
  • Centre de maladies rares CHNO des Quinze Vingt
    Paris, 75012, France
    Recruiting
  • Justus-Liebig Universität - Department of Ophthalmology
    Giessen, 35392, Germany
    Recruiting
  • Klinikum der Ludwig-Maximilian Universität München
    München, 81377, Germany
    Recruiting
  • University of Tuebingen - Inst. for Ophthalmic Research
    Tübingen, 72076, Germany
    Recruiting
  • Radboud Universitair Medisch Centrum
    Nijmegen, 6525 GA, Netherlands
    Recruiting
  • Hospital Sant Joan de Déu (SJD Barcelona Children's Hospital)
    Barcelona, 08950, Spain
    Recruiting
  • Moorfields Eye Hospital NHS Foundation Trust
    London, EC1V 2PD, United Kingdom
    Recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

1 registry update since Sep 25, 2026
Sites
1 site added — first site in Australia. University of Minnesota Medical School is now Withdrawn
Show site
  • Sydney Eye Hospital · Sydney, Australia
Oct 21, 2026
Show all 1 update
  1. Oct 21, 2026
    1 site added — first site in Australia. University of Minnesota Medical School is now Withdrawn
    Show site
    • Sydney Eye Hospital · Sydney, Australia

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06891443
Lead sponsor
Laboratoires Thea
Collaborators
Sepul Bio
Responsible party
Sponsor
First posted
Mar 24, 2025
Start date
Jun 4, 2025
Primary completion
Nov 2027 (estimated)
Completion
Oct 2028 (estimated)
Last update
Oct 21, 2026

Study contacts

Sepul Bio Patient Advocacy Director
Contact
contact@sepulbio.com
+31 617060791
Sepul Bio Chief Medical Officer
Contact

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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