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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01367444
First received: June 3, 2011
Last updated: February 3, 2016
Last verified: February 2016
  Purpose

Primary Objective:

To assess the safety and tolerability of ascending doses of SAR422459 in patients with Stargardt's Macular Degeneration.

Secondary Objective:

To evaluate for possible biological activity of SAR422459.


Condition Intervention Phase
Stargardt Disease
Drug: SAR422459
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa Dose Escalation Safety Study of Subretinally Injected SAR422459, Administered to Patients With Stargardt's Macular Degeneration

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of patients with treatment emergent adverse events [ Time Frame: at 48 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in ocular safety assessments [ Time Frame: at 48 weeks ] [ Designated as safety issue: Yes ]
    Measured as change from baseline in Best Corrected Visual Acuity (BCVA), Slit-lamp, Ophthalmoscopy, Fundus Photography, Intraocular Pressure, Microperimetry, full-field static and kinetic perimetry, OCT and ERG


Secondary Outcome Measures:
  • Delay in retinal degeneration [ Time Frame: at 48 weeks ] [ Designated as safety issue: No ]
    Measured as change from baseline in function relative to untreated contralateral eye on: BCVA, microperimetry, full-field static/kinetic perimetry, OCT and FAF


Estimated Enrollment: 46
Study Start Date: June 2011
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR422459 (Dose 1)
Starting dose of SAR422459 given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection
Experimental: SAR422459 (Dose 2)
Escalating dose of SAR422459 given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection
Experimental: SAR422459 (Dose 3)
Maximum tolerated dose (MTD) of SAR422459 given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection

Detailed Description:

The total duration per patient is up to 52 weeks, which includes a 4 week screening period and a 48 weeks study period.

At the end of the study, the patient will be invited to enter in an open-label safety study and long-term follow-up visits including ophthalmological examinations and recording of adverse events for up to 15 years.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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 perioperative 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 anesthesia (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. Enrolment 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 or signs consistent with unilateral amblyopia (strabismic, anisometropic, or stimulus deprivation).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01367444

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Oregon
Investigational Site Number 840001 Recruiting
Portland, Oregon, United States, 97239-3098
United States, Texas
Investigational Site Number 840004 Recruiting
Houston Nc205, Texas, United States, 77030
France
Investigational Site Number 250001 Recruiting
Paris, France, 75012
Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: Richard Weleber, MD Oregon Health & Science University, Portland, Oregon
Principal Investigator: Jose-Alain Sahel, MD. Ph.D Hopital Nationale des Quinze-Vingt, Paris France
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01367444     History of Changes
Other Study ID Numbers: TDU13583  SG1/001/10 
Study First Received: June 3, 2011
Last Updated: February 3, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Stargardt Disease

Additional relevant MeSH terms:
Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases

ClinicalTrials.gov processed this record on February 11, 2016