Phase I/IIA Study of SAR422459 in Participants With Stargardt's Macular Degeneration

NCT01367444 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: TDU13583SG1/001/10
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 5

Brief Summary

Primary Objective: To assess the safety and tolerability of ascending doses of SAR422459 in participants with Stargardt's Macular Degeneration (SMD). Secondary Objective: To evaluate for possible biological activity of SAR422459.

Conditions

Stargardt's Disease

Keywords

Stargardt's Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the investigational product. The TEAEs were defined as any event that started or increased in severity after the participant received investigational medicinal product (IMP), including abnormal laboratory results, electrocardiogram, etc.

  From Baseline to Week 48

• Percentage of Participants With TEAEs by Severity

  An AE was any unfavorable and unintended physical sign, symptom, or laboratory parameter that developed or worsened in severity during the course of the study, whether or not considered related to the investigational product. For each AE, the severity was categorized as either mild, moderate or severe where 'mild' was defined as discomfort noticed but did not interfere with the participant's daily routines (an annoyance), 'moderate' was defined as some impairment of function, not hazardous to health (uncomfortable or embarrassing), and 'severe' was defined as significant impairment of function, hazardous to health (incapacitating).

  From Baseline to Week 48

Study Arms (3)

SAR422459 (Dose 1)

EXPERIMENTAL

Starting dose of SAR422459 given through subretinal injection

Drug: SAR422459

SAR422459 (Dose 2)

EXPERIMENTAL

Escalating dose of SAR422459 given through subretinal injection

Drug: SAR422459

SAR422459 (Dose 3)

EXPERIMENTAL

Maximum tolerated dose (MTD) of SAR422459 given through subretinal injection

Drug: SAR422459

Interventions

SAR422459 DRUG

Pharmaceutical form: sterile solution, 100 microliters (μL) aliquots in 0.3 milliliter (mL) type I borosilicate glass 'V' vials with a butyl stopper and aluminum crimp seal. Route of administration: subretinal injection

SAR422459 (Dose 1); SAR422459 (Dose 2); SAR422459 (Dose 3)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent obtained from the participant and/or the participant's legally acceptable representative.
• Diagnosis of SMD, with at least one pathogenic mutant ABCA4 allele on each chromosome.
• Women of childbearing potential must had 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.
• Participants must agree to not donate blood, organs, tissues or cells for at least three months following SAR422459 administration.
• Participants enrolled in France must be affiliated to or benefit from a social security regimen.
• Participants (18 years or older) with advanced SMD.
• Visual acuity less than or equal to (\<=) 20/200 in the worst eye.
• Severe cone-rod dysfunction with no detectable or severely abnormal full-field electroretinogram responses.
• Participants (18 years or older) with SMD.
• Visual Acuity \<=20/200 in the worst eye.
• Abnormal full-field electroretinogram responses.
• Participants (18 years or older) with SMD.
• Visual acuity \<=20/100 in the worst eye.
• Abnormal full-field electroretinogram responses.

You may not qualify if:

• Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study outcome measures.
• 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 participant 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 were 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (5)

Investigational Site Number 840002

Miami, Florida, 33136, United States

Location

Investigational Site Number 840005

Iowa City, Iowa, 52242, United States

Location

Investigational Site Number 840001

Portland, Oregon, 97239-3098, United States

Location

Investigational Site Number 840004

Houston, Texas, 77030, United States

Location

Investigational Site Number 250001

Paris, 75012, France

Location

Related Publications (2)

• Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.

  PMID: 30194931 DERIVED

• Parker MA, Choi D, Erker LR, Pennesi ME, Yang P, Chegarnov EN, Steinkamp PN, Schlechter CL, Dhaenens CM, Mohand-Said S, Audo I, Sahel J, Weleber RG, Wilson DJ. Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial. Transl Vis Sci Technol. 2016 Oct 1;5(5):10. doi: 10.1167/tvst.5.5.10. eCollection 2016 Oct.

  PMID: 27730010 DERIVED

MeSH Terms

Conditions

Stargardt Disease

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

The planned analysis was adjusted and carried out on the available safety data collected before the Sponsor's decision to stop SAR422459 development prematurely.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Paul Yang, MD

  Oregon Health & Science University, Portland, Oregon

  PRINCIPAL INVESTIGATOR

• Jose-Alain Sahel, MD. Ph.D

  Hopital Nationale des Quinze-Vingt, Paris France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 7, 2011
• Study Start: June 8, 2011
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: April 14, 2022
• Results First Posted: June 5, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (4); FR (1)