open - label trial with ascending dose to evaluate safety, tolerability and efficacy of EDIT-101 in adult and children with Leber Congenital Amaurosis Type 10 (LCA10)
- Conditions
- eber 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) is an ultra-rare and seriously debilitating disease, usually emerging early in infancy and resulting in significant vision lossMedDRA version: 20.0Level: HLGTClassification code 10015920Term: Eye disorders congenitalSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- EUCTR2019-004981-16-NL
- Lead Sponsor
- Editas Medicine, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method