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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01367444
First received: June 3, 2011
Last updated: March 5, 2015
Last verified: March 2015
  Purpose

Primary Objective:

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

Secondary Objective:

To evaluate for possible biological activity of StarGen™.


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 StarGen™ (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, Visual fields (microperimetry) and Optical Coherence Tomography (OCT)


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, perimetry, ophthalmoscopy, ERG, fundus photography, fundus autoflouroscence, OCT, reading speed, VFQ-25


Estimated Enrollment: 46
Study Start Date: June 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR422459 (Dose 1)
1.8 x 10^5 transducing units (TU)/eye (1:10) of StarGen given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection
Other Name: StarGen™
Experimental: SAR422459 (Dose 2)
6 x 10^5 TU/eye (1:3) of StarGen given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection
Other Name: StarGen™
Experimental: SAR422459 (Dose 3)
1.8 x 10^6 TU/eye (undiluted) in a volume of 300 µL of StarGen given through subretinal injection
Drug: SAR422459
Pharmaceutical form:Prefilled syringes Route of administration: subretinal injection
Other Name: StarGen™

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 will continue for 5 years with visits every 6 months; then the investigator will follow the patient for a subsequent 10 years at a minimum interval of once a year to monitor delayed adverse events.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 screening and at baseline, and agree to use an effective form of contraception, 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 StarGen™ administration.

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:

  • Patients (6 years or older) with Stargardt's Macular Degeneration who are anticipated to experience rapid deterioration in visual function and/or retinal structure in the opinion of the study investigator.
  • Visual acuity ≥20/100 in the worst (study) eye.
  • Mildly abnormal (ie, abnormalities limited to photopic responses) or normal full-field electroretinogram responses.
  • Patients able to understand, willingness to cooperate and ability to reliably perform required study procedures.

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.

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 StarGen™ administration.

Participation in a prior ocular gene transfer therapy study. Enrolment in any other clinical treatment study throughout the duration of the StarGen™ 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: Richard Weleber, M.D 503 494 8386

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239-3098
Principal Investigator: Richard Weleber, MD         
France
Centre Hospitalier Nationale d'Ophthalmologie des Quinze-Vingts Recruiting
Paris, France, 75571
Contact: Jose Sahel, MD. Ph.D         
Principal Investigator: Jose Sahel, MD.Ph.D         
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: March 5, 2015
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 May 26, 2015