Retinitis Pigmentosa, associated with Ushers Syndrome Type 1B. MedDRA version: 20.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10063396 Term: Usher's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: UshStat (SAR421869)
Product Code: Lentiviral vector containing MYO7A gene
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Lentiviral vector containing the human MY07A
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher syndrome type 1B, caused by at least one pathogenic MYO7A mutation on both alleles, confirmed by direct sequencing and co-segregation analysis within the patient's family. Suitable verbal/auditory and/or tactile sign language communication (in the opinion of the investigator) as to allow written informed consent to be obtained. Women of childbearing potential must have a negative pregnancy test at screening and at baseline, and agree to use an effective form of contraception such as the contraceptive pill or intra uterine device for at least three months following SAR421869 administration, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrolment. Males of reproductive potential must agree with their partner to use two forms of contraception, including one barrier method for at least three months following SAR421869 administration if their partner is of childbearing capacity, or must be surgically sterile. Patients must agree to not donate blood, organs, tissues or cells for at least three months following SAR421869 administration. Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Presence of significant ocular abnormalities in the study eye that in the opinion of the investigator would preclude the planned surgery, effective safety follow-up or interfere with the interpretation of study endpoints (eg, glaucoma, corneal or significant lens opacities, pre-existing uveitis, intraocular infection, choroidal neovascularization). Any pre-existing factor or past history of eye disease in children that may predispose to an increased risk of surgical complications in the study eye (eg, trauma, previous surgery, uveitis, congenital, developmental or structural abnormalities). Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function (eg, malignancies, diabetes, juvenile rheumatoid arthritis or sickle cell disease). Any contraindication to pupil dilation in either eye. Contraindications to use of anesthesia (local or general, as appropriate). Treatment with intravitreal, subtenon, or periocular steroid within 4 months of the screening visit. Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study (eg, fluorescein, dilation drops), or medications planned for use during the peri-operative period, particularly topical, injected or systemic corticosteroids. Life-threatening illness. Alcohol or other substance abuse. History of malignancy within a five year period or have had a positive cancer screening test within a one year period of the screening visit. Laboratory test abnormalities or abnormalities in electrocardiogram or chest X-ray, that in the opinion of the principal investigator, are clinically significant and would make the patient unsuitable for participation in the study. Intercurrent illness or infections 28 days prior to SAR421869 administration. Concurrent anti-retroviral therapy that would inactivate the investigational agent. Current treatment with immunosuppressant therapies. Pre-menopausal or non-surgically sterile women who are unwilling to use an effective form of contraception such as the contraceptive pill or intrauterine device. Men or women who do not agree to use barrier contraception as specified in the inclusion criteria. Pregnant or breastfeeding women. History of any investigational agent within 28 days prior to SAR421869 administration. Participation in a prior gene transfer therapy study. Enrolment in any other clinical study, for any condition, including those relating to Usher syndrome Type 1B, throughout the duration of the SAR421869 study. Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery. Past medical history of HIV, or hepatitis A, B or C. Inability to comply with the study protocol. Any ocular surgery including laser and cataract surgery with intraocular lens implantation, aphakia or prior vitrectomy, in the study eye within 6 months of screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in patients with Usher Syndrome type 1B.;Secondary Objective: To evaluate for possible biological activity of SAR421869.;Primary end point(s): The incidence of adverse events. The number and percentage of patients with treatment emergent adverse events.;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine delay in retinal degeneration following the SAR421869 injection. Changes in visual function relative to the untreated contralateral eye utilizing retinal analytical techniques. ;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Countries
France, United States
Contacts
Public ContactDirection des Opérations Cliniques
Sanofi-aventis France
Outcome results
None listed