Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B

NCT01505062 | Terminated Phase 1 Results DMC

• 2 other identifiers: TDU13600US1/001/10
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

Brief Summary

To evaluate the safety and tolerability of ascending doses of subretinal injections of SAR421869 in participants with Usher syndrome type 1B. To evaluate for possible biological activity of SAR421869.

Conditions

Usher Syndrome; Retinitis Pigmentosa

Keywords

Usher Syndrome Retinitis Pigmentosa; Usher Syndrome associated Retinitis Pigmentosa

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 IMP. The TEAEs were defined as any event that started or increased in severity after the participant received 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 IMP. The TEAEs were defined as any event that started or increased in severity after the participant received IMP, including abnormal laboratory results, electrocardiogram, etc. 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 (5)

SAR421869 (Cohort 1)

EXPERIMENTAL

Starting dose of SAR421869 given through one subretinal injection.

Drug: SAR421869

SAR421869 (Cohort 2)

EXPERIMENTAL

Escalating dose of SAR421869 given through one subretinal injection.

Drug: SAR421869

SAR421869 (Cohort 3)

EXPERIMENTAL

Escalating dose of SAR421869 given through one subretinal injection.

Drug: SAR421869

SAR421869 (Cohort 4)

EXPERIMENTAL

Maximum tolerated dose (MTD) of SAR421869 given through one subretinal injection.

Drug: SAR421869

SAR421869 (Cohort 5)

EXPERIMENTAL

MTD of SAR421869 given through one subretinal injection.

Drug: SAR421869

Interventions

SAR421869 DRUG

Formulation: Sterile suspension for intraocular injection, 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

Also known as: UshStat®

SAR421869 (Cohort 1); SAR421869 (Cohort 2); SAR421869 (Cohort 3); SAR421869 (Cohort 4); SAR421869 (Cohort 5)

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:

• Clinical and molecular diagnosis of Retinitis Pigmentosa associated with Usher Syndrome type 1B, caused by at least one pathogenic myosin 7a gene (MYO7A) mutation on both alleles, confirmed by direct sequencing and co-segregation analysis within the participant'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 had 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 agreed with their partner to use two forms of contraception, including one barrier method for at least three months following SAR421869 administration if their partner was of childbearing capacity, or must be surgically sterile.
• Participants agreed to not donate blood, organs, tissues or cells for at least three months following SAR421869 administration.

You may not qualify if:

• 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 outcome measures (e.g., 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 might predispose to an increased risk of surgical complications in the study eye (e.g., 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 (e.g., 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 (e.g., 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 participant unsuitable for participation in the study.
• Intercurrent illness or infection 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 were unwilling to use an effective form of contraception such as the contraceptive pill or intrauterine device.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Investigational Site Number 840001

Portland, Oregon, 97239-3098, United States

Location

Investigational Site Number 250001

Paris, 75012, France

Location

Related Publications (1)

• Zallocchi M, Binley K, Lad Y, Ellis S, Widdowson P, Iqball S, Scripps V, Kelleher M, Loader J, Miskin J, Peng YW, Wang WM, Cheung L, Delimont D, Mitrophanous KA, Cosgrove D. EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat. PLoS One. 2014 Apr 4;9(4):e94272. doi: 10.1371/journal.pone.0094272. eCollection 2014.

  PMID: 24705452 DERIVED

MeSH Terms

Conditions

Usher Syndromes; Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Hearing Loss, Sensorineural; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Blindness; Vision Disorders; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Eye Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The planned analysis was adjusted and carried out only on the available safety and tolerability data collected before the Sponsor's decision to stop SAR421869 development prematurely.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Richard Weleber, MD

  Casey Eye Institute, Portland, Oregon

  PRINCIPAL INVESTIGATOR

• Jose-Alain Sahel, MD, PhD

  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: January 4, 2012
• First Posted: January 6, 2012
• Study Start: March 26, 2012
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: April 28, 2022
• Results First Posted: March 18, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); US (1)