Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of EDIT-101 in Adult and Pediatric Participants with Leber Congenital Amaurosis Type 10 (LCA10), with Centrosomal Protein 290 (CEP290)-Related Retinal Degeneration Caused by a Compound Heterozygous or Homozygous Mutation Involving c.2991+1655A>G in Intron 26 (IVS26) of the CEP290 Gene (*LCA10-IVS26*)
- Conditions
- CEP290-gene mutation and inherited retinal degeneration10015920
- Registration Number
- NL-OMON54872
- Lead Sponsor
- Editas Medicine, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 2
-Adult participants enrolling in Cohorts 1, 2, or 3 must be at least 18 years
of age at the time of informed consent. Pediatric participants enrolling in
Cohorts 4 or 5 must be 3 to 17 years of age, inclusive, at the time of informed
consent.
-CEP290-related retinal degeneration caused by a homozygous or compound
heterozygous mutation involving c.2991+1655A>G in IVS26 of the CEP290 gene
confirmed by DNA sequencing (ie, 1 or 2 intron 26 c.2991+1655A>G mutations) and
100% match for both gRNA and PAM sequences.
-Male or Female.
-A sexually mature male participant must agree to use contraception as detailed
in Section 10.7 of this protocol from the time of informed consent through at
least 12 months after study intervention, and to refrain from donating sperm
during this period.
-A female participant is eligible to participate if she is not pregnant (has a
negative urine pregnancy result prior to study intervention), not
breastfeeding, and at least one of the following conditions applies: Not a
WOCBP as defined in Protocol Section 10.7, OR A WOCBP, or who reaches
childbearing potential during the study, who agrees to follow
the contraceptive guidance in Protocol Section 10.7 from the time of informed
consent through at least 12 months after study intervention.
-The participant (or guardian, in the case of a minor) must provide written
informed consent prior to any study related procedures. Minors must provide
assent in accordance with country and local regulations, as applicable.
-Both eyes must be at least LP. The study eye will be the worse seeing eye and
must meet the following BCVA criteria:
Cohort 1: BWD, WFP, or LP
Cohorts 2 - 5: LP to 0.4 logMAR (20/50 Snellen equivalent). ). Note: The
sentinel participant in each of these cohorts will have severe vision loss with
a logMAR BCVA of >=1.6 to 3.9 (20/800 or worse to LP) in the study eye.
Subsequent participants in each cohort will have LP to 0.4 logMAR (20/50
Snellen equivalent) best-corrected visual acuity in the study eye. If both eyes
have the same BCVA but the worse seeing eye (as determined by the participant
and the examiner) does not meet the above criteria, the better seeing eye may
be designated as the study eye as long as the participant agrees and the better
seeing eye meets all eligibility criteria.
-Photoreceptor ONL identifiable in fovea by spectral domain OCT in the study
eye.
-Able, as assessed by the investigator, and willing to complete study
assessments and follow study instructions for the duration of the study.
-If currently enrolled in Study EDIT-NHS01 (the Natural History Study of
CEP290-Related Retinal Degeneration), the participant must agree to complete
the early
termination visit for that study, and be withdrawn from that study, before
enrolling in this study.
-Other known disease-causing mutations documented in the participant's medical
history or identified through the retinal dystrophy gene panel evaluation
performed at screening (including but not limited to bi-allelic mutations in
other genes known to cause LCA) that, in the opinion of the investigator, would
interfere with the potential therapeutic effect of the investigational product
or the quality of the assessments.
-Achieves a passing score for the Visual Function Navigation course at the
maximum level of difficulty (ie, passes the most challenging Visual Function
Navigation course under the
dimmest lighting conditions) with either eye independently or both eyes
together.
-In either eye, cataract surgery in the last 3 months before the screening
visit.
-In either eye, any active ocular/intraocular infection or inflammation (such
as blepharitis, infectious conjunctivitis, keratitis, scleritis,
endophthalmitis, idiopathic or autoimmune-associated uveitis, or herpetic
lesions), assessed at screening.
-In either eye, history of steroid-responsive intraocular pressure increases
such that the affected eye had a pressure > 25 mm Hg following corticosteroid
exposure despite topical
intraocular-pressure-lowering pharmacologic therapy.
-In either eye, Argus retinal implant.
-In the study eye, absence of clear ocular media and adequate pupil dilation,
assessed at screening, to permit good quality OCT images.
-In the study eye, presence of vitreous hemorrhage.
-In the study eye, any history of rhegmatogenous retinal detachment.
-In the study eye, spherical equivalent of the refractive error demonstrating
more than -8 diopters of myopia and more than +6 diopters of hyperopia (prior
to cataract or refractive surgery), assessed at screening.
-Uncontrolled diabetes mellitus (hemoglobin A1c >=10%) in the last 3 months
before the screening visit or at screening.
-Active gastric ulcer at screening.
-Use of systemic immunosuppressive medications for any chronic disease in the
last 3 months before the screening visit, or during the screening period.
-Any vaccination/immunization in the last 28 days before screening, or during
the screening period.
-An inability or unwillingness to take the course of oral prednisone that is
required in this study.
-Current enrollment in an investigational interventional drug or device study
(ocular or non-ocular) or participation in such a study within 6 months before
the screening visit.
(This does not include observational studies. Prior or current participation in
Study EDIT-NHS01 is not an exclusion.)
-Received prior gene therapy or oligonucleotide treatment of any kind.
-The participant has a condition or is in a situation which, in the
investigator's or operating surgeon's opinion, may put the participant at
significant risk, may confound the study results, or may interfere
significantly with the participant's participation in the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Incidence of DLT, as detailed in Section 8.3.8.1 of the protocol<br /><br>• Frequency of AEs related to EDIT-101<br /><br>• Number of procedural related AEs</p><br>
- Secondary Outcome Measures
Name Time Method