Trial Outcomes & Findings for Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert (NCT NCT01694186)

Last Updated: 2021-04-02

Results Overview

Safety: Ocular adverse events, including IOP elevation; medications/procedures required to control elevated IOP; development or worsening of cataract; cataract-related procedures; clinically significant ocular changes; procedure related adverse events Primary Efficacy Endpoint: Proportion of subjects who have a recurrence of uveitis in the study eye within 6 months after receiving study treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

129 participants

Primary outcome timeframe

36 months

Results posted on

2021-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	Sham Injection sham injection Sham injection	FAI Insert FAI insert (0.18 mg fluocinolone acetonide) FAI insert
Overall Study STARTED	42	87
Overall Study COMPLETED	36	80
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Injection n=42 Participants Sham injection Sham injection	FAI Insert n=87 Participants FAI insert (0.18 mg fluocinolone acetonide) FAI insert	Total n=129 Participants Total of all reporting groups
Age, Continuous	48.3 years STANDARD_DEVIATION 13.71 • n=5 Participants	48.3 years STANDARD_DEVIATION 13.90 • n=7 Participants	48.3 years STANDARD_DEVIATION 13.79 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	50 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	37 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	21 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	60 Participants n=7 Participants	86 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Hungary	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	37 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	16 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Israel	4 participants n=5 Participants	6 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Germany	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment India	11 participants n=5 Participants	20 participants n=7 Participants	31 participants n=5 Participants
ITT and Safety populations ITT	42 Participants n=5 Participants	87 Participants n=7 Participants	129 Participants n=5 Participants
ITT and Safety populations Safety	42 Participants n=5 Participants	87 Participants n=7 Participants	129 Participants n=5 Participants

PRIMARY outcome

Timeframe: 36 months

Population: Proportion of Subjects with Recurrence of Uveitis in the Study Eye at 36 Months (ITT Population) Overall Summary of Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit (Safety Population)

Outcome measures

Outcome measures
Measure	Sham Injection n=42 Participants sham injection Sham injection The sham applicator was an empty 1-mL syringe attached to a blunt 14-gauge needle; it did not contain an FAI insert. During study Day 1, the sham applicator was gently pressed against the study eye to provide the subject with the perception that an intravitreal injection was being performed. This procedure was performed to mask study subjects to their assigned treatment.	FAI Insert n=87 Participants FAI insert (0.18 mg fluocinolone acetonide) One treatment (FAI injection) was administered on Day 1 to each subject. The Fluocinolone Acetonide Intravitreal Insert (FAI insert) is an injectable intravitreal sustained-release FA delivery system preloaded into an injection device. Each insert contained a drug core of FA as the active ingredient within a cylindrical polyimide polymer tube 3.5-mm long with an external diameter of 0.37 mm. The dose delivered in the FAI insert was 0.18 mg fluocinolone acetonide delivered into the vitreous humor for 36 months. The FAI insert was administered to the study eye by injection through the pars plana using a preloaded applicator with a 25-gauge needle.
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Protocol-Defined Recurrence of Uveitis	12 Participants	5 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular TEAE	39 Participants	77 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular Serious TEAE	12 Participants	16 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular Treatment- Related TEAE	21 Participants	60 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular Treatment-Related Serious TEAE	2 Participants	11 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular TEAE leading to treatment discontinuation	0 Participants	0 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular TEAE leading to study discontinuation	0 Participants	0 Participants
Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit Ocular AE leading to death	0 Participants	0 Participants

Adverse Events

Sham Injection

Serious events: 17 serious events

Other events: 40 other events

Deaths: 0 deaths

FAI Insert

Serious events: 29 serious events

Other events: 84 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Affairs

Eyepoint Pharmacueticals

Phone: 6179726204

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sham Injection n=42 participants at risk sham injection Sham injection	FAI Insert n=87 participants at risk FAI insert (0.18 mg fluocinolone acetonide) FAI insert
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Cardiac disorders Angina pectoris	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Cardiac disorders Myocardial infarction	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Cardiac disorders Supraventricular tachycardia	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Gastrointestinal disorders Diarrhoea	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Gastrointestinal disorders Duodenitis	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Nervous system disorders Central nervous system lesion	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Nervous system disorders Presyncope	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Nervous system disorders Transient ischaemic attack	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Blood and lymphatic system disorders Lymphadenopathy	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Congenital, familial and genetic disorders Hydrocele	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Infections and infestations Septic shock	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Injury, poisoning and procedural complications Skull fracture	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Metabolism and nutrition disorders Obesity	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Pregnancy, puerperium and perinatal conditions Premature baby	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Psychiatric disorders Post-traumatic stress disorder	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Blindness	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Cataract	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	8.0% 7/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Cystoid macular oedema	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Glaucoma	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Hypotony of eye	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Macular oedema	4.8% 2/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Non-infectious endophthalmitis	4.8% 2/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Ocular hypertension	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Retinal detachment	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Uveitis	9.5% 4/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Vitreous haemorrhage	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Vitritis	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Investigations Intraocular pressure fluctuation	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Investigations Intraocular pressure increased	2.4% 1/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Injury, poisoning and procedural complications Post-procedural inflammation	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Nervous system disorders Optic neuritis	0.00% 0/42 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)

Measure	Sham Injection n=42 participants at risk sham injection Sham injection	FAI Insert n=87 participants at risk FAI insert (0.18 mg fluocinolone acetonide) FAI insert
Vascular disorders Hypertension	9.5% 4/42 • Number of events 4 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	6.9% 6/87 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Investigations Intraocular pressure increased	31.0% 13/42 • Number of events 13 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	32.2% 28/87 • Number of events 28 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Respiratory, thoracic and mediastinal disorders Cough	9.5% 4/42 • Number of events 4 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Nervous system disorders Headache	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	6.9% 6/87 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Anterior chamber flare	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Cataract	14.3% 6/42 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	37.9% 33/87 • Number of events 33 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Cataract subcapsular	9.5% 4/42 • Number of events 4 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	6.9% 6/87 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Conjunctival haemorrhage	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	14.9% 13/87 • Number of events 13 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Cystoid macular oedema	28.6% 12/42 • Number of events 12 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	13.8% 12/87 • Number of events 12 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Dry eye	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	17.2% 15/87 • Number of events 15 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Eye pain	21.4% 9/42 • Number of events 9 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	12.6% 11/87 • Number of events 11 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Eye pruritus	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Eyelid ptosis	2.4% 1/42 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Foreign body sensation in eyes	4.8% 2/42 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	9.2% 8/87 • Number of events 8 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Iridocyclitis	14.3% 6/42 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	1.1% 1/87 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Macular fibrosis	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Macular oedema	38.1% 16/42 • Number of events 16 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	6.9% 6/87 • Number of events 6 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Ocular discomfort	2.4% 1/42 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Ocular hyperaemia	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	8.0% 7/87 • Number of events 7 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Photopsia	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Posterior capsule opacification	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Uveitis	61.9% 26/42 • Number of events 26 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	20.7% 18/87 • Number of events 18 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Vision blurred	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Visual acuity reduced	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	18.4% 16/87 • Number of events 16 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Visual impairment	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	9.2% 8/87 • Number of events 8 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Vitreous floaters	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	9.2% 8/87 • Number of events 8 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Eye disorders Vitreous opacities	9.5% 4/42 • Number of events 4 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
General disorders Fatigue	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	0.00% 0/87 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
General disorders Pain	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Psychiatric disorders Depression	2.4% 1/42 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Gastrointestinal disorders Nausea	9.5% 4/42 • Number of events 4 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	3.4% 3/87 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Endocrine disorders Hypothyroidism	2.4% 1/42 • Number of events 1 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	5.7% 5/87 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Infections and infestations Nasopharyngitis	11.9% 5/42 • Number of events 5 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	13.8% 12/87 • Number of events 12 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Infections and infestations Viral upper respiratory tract infection	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)
Infections and infestations Conjunctivitis	7.1% 3/42 • Number of events 3 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)	2.3% 2/87 • Number of events 2 • 3 years Treatment-Emergent Non-Ocular Adverse Events Through Month 36 Visit by System Organ Class and Preferred Term, Greater than 5% of Subjects in Either Treatment Group (Safety Population)