A Phase I/IIa Study of SAR422459 in Patients With Stargardt Macular Degeneration

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2010-023111-34-NL
• Date of registration: 04/02/2016
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche et développement
• Public title: A Phase I/IIa Study of SAR422459 in Patients With Stargardt Macular Degeneration
• Scientific title: A Phase I/IIa Dose Escalation Safety Study of Subretinally Injected SAR422459, Administered to Patients with Stargardt's Macular Degeneration.
• Date of first enrolment: 24/02/2016
• Target sample size: 46
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023111-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Italy, Netherlands, United States

Contacts

• Name: CSU team manager
• Affiliation: sanofi-aventis the Netherlands bv

• Name: CSU team manager
• Affiliation: sanofi-aventis the Netherlands bv

Key inclusion & exclusion criteria

Inclusion criteria:
-Signed and dated written informed consent obtained from the patient and/or the patient's legally acceptable representative.

-Diagnosis of Stargardt's Macular Degeneration, with at least one pathogenic mutant ABCA4 allele on each chromosome.

-Women of childbearing potential must have a negative pregnancy test at Day -1, and agree to use an effective form of contraception for at least three months, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrollment .

-Males must agree with their partner to use two forms of contraception for at least three months following SAR422459 administration.

-Patients enrolled in France must be affiliated to or benefit from a social security regimen.

-Specific Inclusion Criteria Patient Group A:
-Patients (18 years or older) with Advanced Stargardt's Macular degeneration.
-Visual acuity =20/200 in the worst eye
-Severe cone-rod dysfunction with no detectable or severely abnormal full-field
electroretinogram responses.

-Specific Inclusion Criteria Patient Group B:
-Patients (18 years or older) with Stargardt’s Macular Degeneration.
-Visual Acuity =20/200 in the worst eye.
-Abnormal full-field electroretinogram responses.

-Specific Inclusion Criteria Patient Group C:
-Patients (18 years or older) with Stargardt’s Macular Degeneration.
-Visual acuity =20/100 in the worst eye.
-Abnormal full-field electroretinogram responses.

-Specific Inclusion Criteria Patient Group D:
-Symptomatic patients (6 years and older) with childhood or young adult onset
Stargardt's Macular Degeneration (eg, before age 26) with at least one
pathogenic mutant ABCA4 allele on each chromosome confirmed by direct
sequencing and co-segregation analysis within the patient’s family.
-Visual acuity of =20/200 in both eyes at the time of the screening visit.
-Patients are anticipated to experience rapid deterioration in visual function
and/or retinal structure in the opinion of the study Investigator.

NOTE: GROUP D WILL BE OPEN FOR RECRUITMENT ONLY AFTER AUTHORIZATION.


Are the trial subjects under 18? yes
Number of subjects for this age range: 14
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints.

-Cataract surgery with intraocular lens implantation within 6 months of enrolment.

-Aphakia or prior vitrectomy in the study eye.

-Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function.

-Any intraocular surgery or laser in either eye planned within 6 months of Day 0.

-Any contraindication to pupil dilation in either eye.

-Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study, or medications planned for use in the peri-operative period, particularly topical, injected or systemic corticosteroids.

-Any injectable intravitreal treatment to the treated eye or intravitreal device in the treated eye within 6 months prior to screening.

-Any periocular injections of corticosteroids to the treated eye within 4 months prior to screening.

-Laboratory test abnormalities or abnormalities in electrocardiogram, chest X rays that in the opinion of the principal investigator, would make the patient unsuitable for participation in the study.

-Significant intercurrent illness or infection during the 28 days prior to enrolment.

-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.

-Alcohol or other substance abuse.

-Contraindications to use of anaesthesia (local or general, as appropriate).

-Concurrent anti-retroviral therapy that would inactivate the investigational agent.

-History of any investigational agent within 28 days prior to SAR422459 administration.

-Participation in a prior ocular gene transfer therapy study.

-Enrollment in any other clinical treatment study throughout the duration of the SAR422459 study.

-Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery.

-A past medical history of human immunodeficiency virus (HIV) or hepatitis A, B or C infection.

-Women who are pregnant or are breastfeeding.

-History of or signs consistent with unilateral amblyopia (strabismic, anisometropic or stimulus deprivation).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stargardt Macular Dystrophy, also known as fundus flavimaculatus or Stargardt disease.
MedDRA version: 18.1 Level: PT Classification code 10062766 Term: Stargardt's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Product Name: SAR422459
Product Code: Lentiviral vector containing ABCA4 gene
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: SAR422459
Current Sponsor code: SAR422459
Concentration unit: U unit(s)
Concentration type: range
Concentration number: 180000-1800000

Primary Outcome(s)

Primary end point(s): Number of patients with treatment emergent adverse events

Change from baseline in ocular safety assessments

Measured as change from baseline in Best Corrected Visual Acuity, Slit-lamp, Ophthalmoscopy, Fundus Photography, Intraocular Pressure, Microperimetry, full-field static and kinetic perimetry, OCT and ERG

Main Objective: To assess the safety and tolerability of ascending doses of SAR422459 in patients with Stargardt Macular Degeneration.

Timepoint(s) of evaluation of this end point: at 48 weeks

Secondary Objective: To evaluate for possible biological activity of SAR422459.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at 48 weeks

Secondary end point(s): Delay in retinal degeneration

Measured as change from baseline in function relative to untreated contralateral eye on: BCVA, microperimetry, full-field static/kinetic perimetry, OCT and FAF

Secondary ID(s)

SG1/001/10(TDU13583)

Source(s) of Monetary Support

sanofi-aventis recherche et développement