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    Summary
    EudraCT Number:2019-004981-16
    Sponsor's Protocol Code Number:1991-201-008
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-07-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2019-004981-16
    A.3Full title of the trial
    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”)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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)
    A.3.2Name or abbreviated title of the trial where available
    EDIT-101 Single Ascending Dose Study in Participants with LCA10-IVS26
    A.4.1Sponsor's protocol code number1991-201-008
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03872479
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEditas Medicine, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEditas Medicine, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEditas Medicine, Inc.
    B.5.2Functional name of contact pointPatient Inquiries
    B.5.3 Address:
    B.5.3.1Street Address11 Hurley Street
    B.5.3.2Town/ city Cambridge
    B.5.3.3Post codeMA 02141
    B.5.3.4CountryUnited States
    B.5.4Telephone number617-401-9007
    B.5.6E-mailpatients@editasmed.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1928.
    D.3 Description of the IMP
    D.3.1Product nameAAV5-CEP290gRNAs323/64-GRK1-SaCas9
    D.3.2Product code EDIT-101
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubretinal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEDIT-101 (also known as AGN-151587)
    D.3.9.1CAS number n/a
    D.3.9.2Current sponsor codeEDIT-101
    D.3.9.3Other descriptive nameAdeno-associated viral vector serotype 5 encoding Staphylococcus aureus Cas9 endonuclease and two guide RNAs complementary to two regions of intron 26 of the CEP290 gene
    D.3.10 Strength
    D.3.10.1Concentration unit vector genomes (vg)/mL
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number≥1.0E12 vg/mL to ≥3.0E12 vg/mL
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
    D.3.11.3.5.1CAT classification and reference numberGene therapy medicinal product - EMA/357208/2016
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    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") is an ultra-rare and seriously debilitating disease, usually emerging early in infancy and resulting in significant vision loss
    E.1.1.1Medical condition in easily understood language
    Leber Congenital Amaurosis (LCA)" instead of "LCA10-IVS26

    Leber Congenital Amaurosis type 10 retinal degeneration due to a specific mutation in intron 26
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLGT
    E.1.2Classification code 10015920
    E.1.2Term Eye disorders congenital
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and tolerability of a single dose of AGN-151587 when administered to participants with LCA10-IVS26 mutation”
    E.2.2Secondary objectives of the trial
    To evaluate different doses of EDIT-101 for subsequent clinical
    evaluation.
    To evaluate the efficacy of a single dose of EDIT-101 on: Visual
    Function Navigation (Ora-VNC); Visual acuity; Pupillometry; Oculomotor
    control and instability (OCI); Full field light sensitivity threshold (FST);
    OCT; Contrast sensitivity; Microperimetry; Kinetic perimetry; Color
    vision; QoL
    Exploratory:
    To evaluate an immune response to EDIT-101 .
    To evaluate viral shedding in blood, nasal mucosa, semen, and tears
    Fundus autofluorescence (FAF and NIRAF)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    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.
    E.4Principal exclusion criteria
    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.
    E.5 End points
    E.5.1Primary end point(s)
    Incidence of DLT, as detailed in Section 8.3.8.1
    Frequency of AEs related to EDIT-101
    Number of procedural related AEs
    E.5.1.1Timepoint(s) of evaluation of this end point
    Incidence of DLT before visits Week 4 and Week 6
    AE - through whole study
    E.5.2Secondary end point(s)
    Maximum tolerated dose as determined by DLT
    E.5.2.1Timepoint(s) of evaluation of this end point
    Change from baseline in the following parameters:
    - Visual Function Navigation course score of the study eye, contralateral eye, and both eyes together;
    - logMAR measurement of BCVA;
    - Pupil size in dark and in light ( pupil constriction; velocity, maximum pupil constriction velocity, amount of constriction after stimulus, percent of constriction after stimulus;
    - Gaze tracking;
    - Dark adapted visual sensitivity to white, red, and blue light;
    - The thickness of the ONL and integrity of the ellipsoid zone;
    - LogMAR measurement of contrast sensitivity.;
    - Macular sensitivity;
    - Visual field; Farnsworth 15 score;
    - QoL questionnaires;
    - Global Impressions of Change;
    - Global Impressions of Severity;
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    United States
    Germany
    Netherlands
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the date of the last visit of the last
    participant in the study.
    A participant is considered to have completed the study if he/she has
    completed all the study
    visits including the End of Study (EOS) visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 8
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 4
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 4
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children (2-11years)
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 4
    F.4.2.2In the whole clinical trial 18
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After end of study or leaving the study early (prior to receiving EDIT-101, patient will no longer have access to the study drug. Following study completion or leaving the study early, patient should discuss other available therapies with the study doctor
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-07-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-06-17
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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