A Phase I/IIA Dose Escalation Safety Study of Subretinally Injected SAR422459, Administered to Patients With Stargardt's Macular Degeneration
Overview
- Phase
- Phase 1
- Intervention
- SAR422459
- Conditions
- Stargardt's Disease
- Sponsor
- Sanofi
- Enrollment
- 27
- Locations
- 5
- Primary Endpoint
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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.
Detailed Description
The total duration per participant was up to 52 weeks, which included 4 week screening period and 48 weeks study period. At the end of the study, the participants were invited to enter in an open-label safety study (LTS13588-NCT01736592) for long-term follow-up visits including ophthalmological examinations and recording of adverse events (AEs) for up to 15 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Specific Inclusion Criteria Participant Group A:
- •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.
Exclusion Criteria
- •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
- •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.
Arms & Interventions
SAR422459 (Dose 2)
Escalating dose of SAR422459 given through subretinal injection
Intervention: SAR422459
SAR422459 (Dose 1)
Starting dose of SAR422459 given through subretinal injection
Intervention: SAR422459
SAR422459 (Dose 3)
Maximum tolerated dose (MTD) of SAR422459 given through subretinal injection
Intervention: SAR422459
Outcomes
Primary Outcomes
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: From Baseline to Week 48
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.
Percentage of Participants With TEAEs by Severity
Time Frame: From Baseline to Week 48
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).