FAI: Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert

• Sponsor: EyePoint Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01694186
• Collaborator: (none)
• Enrollment: 129
• Locations: 34
• Arms: 2
• Actual Duration (Months): 55.8
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study to evaluate the safety and efficacy of an FAI insert for the management of subjects with non-infectious uveitis affecting the posterior segment of the eye.

Condition or Disease	Intervention/Treatment	Phase
Non-Infectious Uveitis	Drug: FAI insert; Drug: Sham injection	Phase 3

Detailed Description

This is a phase 3, multi-national, multi-center, randomized, masked, controlled study to evaluate the safety and efficacy of an injectable fluocinolone acetonide intravitreal (FAI) insert for the management of subjects with non-infectious uveitis affecting the posterior segment of the eye. Patients will be randomized to receive either a sham injection or the FAI insert and will be observed for three years following treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multi-National, Multi-Center, Randomized, Masked, Controlled, Safety and Efficacy Study of a Fluocinolone Acetonide Intravitreal Insert in Subjects With Chronic Non-Infectious Uveitis Affecting the Posterior Segment of the Eye
• Actual Study Start Date: Aug 2, 2013
• Actual Primary Completion Date: Mar 26, 2018
• Actual Study Completion Date: Mar 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: sham injection sham injection	Drug: Sham injection; Other Names: Sham Comparator
Experimental: FAI insert FAI insert (0.18 mg fluocinolone acetonide)	Drug: FAI insert; Other Names: Active Drug

Outcome Measures

Primary Outcome Measures

1. 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 [36 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Male or non-pregnant female at least 18 years of age at time of consent

• One or both eyes having a history of recurrent non-infectious uveitis affecting the posterior segment of the eye with or without anterior uveitis > 1 year duration.

• During the 12 months prior to enrollment (Day 1), the study eye has either received treatment:

• systemic corticosteroid or other systemic therapies given for at least 3 months, and/or

• at least 2 intra- or peri-ocular injections of corticosteroid for management of uveitis

OR the study eye has experienced recurrence:

• at least 2 separate recurrences of uveitis requiring systemic, intra- or peri-ocular injection of corticosteroid

• At the time of enrollment (Day 1), study eye has < 10 anterior chamber cells/HPF and a vitreous haze ≤ grade 2.

• Visual acuity of study eye is at least 15 letters on the ETDRS chart

• Subject is not planning to undergo elective ocular surgery during the study

• Subject has ability to understand and sign the Informed Consent Form

• Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria

• Allergy to fluocinolone acetonide or any component of the FAI insert

• History of posterior uveitis only that is not accompanied by vitritis or macular edema

• History of iritis only and no vitreous cells, anterior chamber cells or vitreous haze

• Uveitis with infectious etiology

• Vitreous hemorrhage

• Intraocular inflammation associated with a condition other than noninfectious uveitis (e.g. intraocular lymphoma)

• Ocular malignancy in either eye, including choroidal melanoma

• Toxoplasmosis scar in study eye; or scar related to previous viral retinitis

• Previous viral retinitis

• Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye or fungal diseases of ocular structure

• Media opacity precluding evaluation of retina and vitreous

• Peripheral retinal detachment in area of insertion

• Diagnosis of any form of glaucoma or ocular hypertension in study eye at Screening, unless study eye has been previously treated with an incisional surgery procedure that has resulted in stable IOP in the normal range (10-21 mmHg)

• Intraocular pressure (IOP) > 21 mmHg or concurrent therapy at screening with any IOP-lowering pharmacologic agent in the study eye

• Chronic hypotony (< 6 mmHg)

• Ocular surgery on the study eye within 3 months prior to study Day 1

• Capsulotomy in study eye within 30 days prior to study Day 1

• Prior intravitreal treatment of study eye with Retisert within 36 months prior to study Day 1

• Prior intravitreal treatment of study eye with Ozurdex within 6 months prior to study Day 1

• Prior intravitreal treatment of study eye with Triesence or Trivaris within 3 months prior to study Day 1

• Prior peri-ocular or subtenon steroid treatment of study eye within 3 months prior to study Day 1

• Subjects requiring chronic systemic or inhaled corticosteroid therapy (>15mg prednisone daily) or chronic systemic immunosuppressive therapy

• Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to study Day 1

• Subjects who test positive for human immune deficiency virus (HIV) or syphilis during screening

• Mycobacterial uveitis or chorio-retinal changes of either eye which, in the opinion of the Investigator, result from infectious mycobacterial uveitis

• Systemic infection within 30 days prior to study Day 1

• Any severe acute or chronic medical or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the subject inappropriate for entry into this study

• Any other systemic or ocular condition which, in the judgment of the investigator, could make the subject inappropriate for entry into this study

• Treatment with an investigational drug or device within 30 days prior to study Day 1

• Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 14 days prior to study Day 1 until the Month 12 Visit

• Subjects unlikely to comply with the study protocol or who are likely to be lost to follow-up within three years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Vitreaous Associates	Beverly Hills	California	United States	90211
2	Retinal Consultants Medical Group, Inc	Sacramento	California	United States	95819
3	Retina Macula Institute	Torrance	California	United States	90503
4	Retina Consultants of Southern Colorado	Colorado Springs	Colorado	United States	80909
5	Northwestern University	Chicago	Illinois	United States	60611
6	Ophthalmology & Visual Sciences	Lexington	Kentucky	United States	40508
7	Ocular Immunology and Uveitis Foundation	Cambridge	Massachusetts	United States	02142
8	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
9	Retina Consultants	Slingerlands	New York	United States	12159
10	Duke University Eye Center	Durham	North Carolina	United States	27710
11	Cleveland Clinic	Cleveland	Ohio	United States	44195
12	OHSU Casey Eye Institute	Portland	Oregon	United States	97239
13	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
14	Texas Retina Associates	Arlington	Texas	United States	76012
15	Retina Consultants of Houston	Houston	Texas	United States	77030
16	Foresight Studies, LLC	San Antonio	Texas	United States	78240
17	Augenarzte am St. Franziskus Hospital	Munster		Germany
18	Universitatsklinikum Tubingen	Tubingen		Germany
19	Bajcsy-Zsilinszky Kórház és Rendelőintézet	Budapest		Hungary
20	L. V. Prasad Eye Institute - Hospital	Hyderabad	Andhra Pradesh	India
21	L.V. Prasad Eye Institute	Patia	Bhubaneshwar	India
22	C.H Nagri Municipal Eye Hospital	Ahmedabad	Gujarat	India
23	Seth G.S. Medical College & KEM Hospital	Parel	Mumbai	India
24	PBMA'S H.V. Desai Eye Hospital	Hadapsar	Pune	India
25	King George's Medical University	Lucknow	Uttar Pradesh	India
26	Hadassah University Hospital Ein Kerem	Jerusalem		Israel
27	Rabin Medical Center	Petah Tikva		Israel
28	Sheba Medical Center	Qiryat Ono		Israel
29	Royal Hospitals Trust	Belfast		United Kingdom
30	Birmingham and Midland Eye Centre	Birmingham		United Kingdom
31	Bradford Royal Infirmary	Bradford		United Kingdom
32	Gloucestershire Royal Hospital	Gloucester		United Kingdom
33	Moorfields Eye Hospital	London		United Kingdom
34	St Thomas Hospital	London		United Kingdom

Sponsors and Collaborators

• EyePoint Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Glenn Jaffe, MD, Duke University Eye Center

Study Documents (Full-Text)

• Study Protocol - Oct 20, 2015
• Statistical Analysis Plan - Jan 5, 2017

More Information

Publications

None provided.

• Responsible Party: EyePoint Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01694186
• Other Study ID Numbers: PSV-FAI-001
• First Posted: Sep 27, 2012
• Last Update Posted: Apr 2, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Uveitis

Study Results

Participant Flow

Arm/Group Title	Sham Injection	FAI Insert
Arm/Group Description	sham injection Sham injection	FAI insert (0.18 mg fluocinolone acetonide) FAI insert
Period Title: Overall Study
STARTED	42	87
COMPLETED	36	80
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Sham Injection	FAI Insert	Total
Arm/Group Description	Sham injection Sham injection	FAI insert (0.18 mg fluocinolone acetonide) FAI insert	Total of all reporting groups
Overall Participants	42	87	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (13.71)	48.3 (13.90)	48.3 (13.79)
Sex: Female, Male (Count of Participants)
Female	29 69%	50 57.5%	79 61.2%
Male	13 31%	37 42.5%	50 38.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	12 28.6%	21 24.1%	33 25.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 7.1%	4 4.6%	7 5.4%
White	26 61.9%	60 69%	86 66.7%
More than one race	1 2.4%	2 2.3%	3 2.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Hungary	1 2.4%	0 0%	1 0.8%
United States	19 45.2%	37 42.5%	56 43.4%
United Kingdom	4 9.5%	16 18.4%	20 15.5%
Israel	4 9.5%	6 6.9%	10 7.8%
Germany	3 7.1%	8 9.2%	11 8.5%
India	11 26.2%	20 23%	31 24%
ITT and Safety populations (Count of Participants)
ITT	42 100%	87 100%	129 100%
Safety	42 100%	87 100%	129 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Sham Injection	FAI Insert
Arm/Group Description	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 (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.
Measure Participants	42	87
Protocol-Defined Recurrence of Uveitis	12 28.6%	5 5.7%
Ocular TEAE	39 92.9%	77 88.5%
Ocular Serious TEAE	12 28.6%	16 18.4%
Ocular Treatment- Related TEAE	21 50%	60 69%
Ocular Treatment-Related Serious TEAE	2 4.8%	11 12.6%
Ocular TEAE leading to treatment discontinuation	0 0%	0 0%
Ocular TEAE leading to study discontinuation	0 0%	0 0%
Ocular AE leading to death	0 0%	0 0%

Adverse Events

Time Frame	3 years
Adverse Event Reporting Description	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)
Arm/Group Title	Sham Injection		FAI Insert
Arm/Group Description	sham injection Sham injection		FAI insert (0.18 mg fluocinolone acetonide) FAI insert
All Cause Mortality
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		1/87 (1.1%)
Serious Adverse Events
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/42 (40.5%)		29/87 (33.3%)
Blood and lymphatic system disorders
Lymphadenopathy	1/42 (2.4%)		0/87 (0%)
Cardiac disorders
Angina pectoris	1/42 (2.4%)		0/87 (0%)
Myocardial infarction	0/42 (0%)		1/87 (1.1%)
Supraventricular tachycardia	0/42 (0%)		1/87 (1.1%)
Congenital, familial and genetic disorders
Hydrocele	0/42 (0%)		1/87 (1.1%)
Eye disorders
Blindness	1/42 (2.4%)		0/87 (0%)
Cataract	1/42 (2.4%)		7/87 (8%)
Cystoid macular oedema	0/42 (0%)		1/87 (1.1%)
Glaucoma	1/42 (2.4%)		1/87 (1.1%)
Hypotony of eye	1/42 (2.4%)		0/87 (0%)
Macular oedema	2/42 (4.8%)		0/87 (0%)
Non-infectious endophthalmitis	2/42 (4.8%)		0/87 (0%)
Ocular hypertension	0/42 (0%)		1/87 (1.1%)
Retinal detachment	0/42 (0%)		1/87 (1.1%)
Uveitis	4/42 (9.5%)		2/87 (2.3%)
Vitreous haemorrhage	1/42 (2.4%)		0/87 (0%)
Vitritis	0/42 (0%)		1/87 (1.1%)
Gastrointestinal disorders
Diarrhoea	1/42 (2.4%)		0/87 (0%)
Duodenitis	0/42 (0%)		1/87 (1.1%)
Upper gastrointestinal haemorrhage	0/42 (0%)		1/87 (1.1%)
Infections and infestations
Septic shock	0/42 (0%)		1/87 (1.1%)
Injury, poisoning and procedural complications
Skull fracture	0/42 (0%)		1/87 (1.1%)
Post-procedural inflammation	0/42 (0%)		1/87 (1.1%)
Investigations
Intraocular pressure fluctuation	0/42 (0%)		1/87 (1.1%)
Intraocular pressure increased	1/42 (2.4%)		2/87 (2.3%)
Metabolism and nutrition disorders
Obesity	0/42 (0%)		1/87 (1.1%)
Musculoskeletal and connective tissue disorders
Foot deformity	0/42 (0%)		1/87 (1.1%)
Osteoarthritis	0/42 (0%)		2/87 (2.3%)
Rhabdomyolysis	0/42 (0%)		1/87 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer	1/42 (2.4%)		0/87 (0%)
Nervous system disorders
Central nervous system lesion	1/42 (2.4%)		0/87 (0%)
Presyncope	0/42 (0%)		1/87 (1.1%)
Transient ischaemic attack	1/42 (2.4%)		0/87 (0%)
Optic neuritis	0/42 (0%)		1/87 (1.1%)
Pregnancy, puerperium and perinatal conditions
Premature baby	0/42 (0%)		1/87 (1.1%)
Psychiatric disorders
Post-traumatic stress disorder	1/42 (2.4%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/42 (95.2%)		84/87 (96.6%)
Endocrine disorders
Hypothyroidism	1/42 (2.4%)	1	5/87 (5.7%)	5
Eye disorders
Anterior chamber flare	3/42 (7.1%)	3	0/87 (0%)	0
Cataract	6/42 (14.3%)	6	33/87 (37.9%)	33
Cataract subcapsular	4/42 (9.5%)	4	6/87 (6.9%)	6
Conjunctival haemorrhage	5/42 (11.9%)	5	13/87 (14.9%)	13
Cystoid macular oedema	12/42 (28.6%)	12	12/87 (13.8%)	12
Dry eye	5/42 (11.9%)	5	15/87 (17.2%)	15
Eye pain	9/42 (21.4%)	9	11/87 (12.6%)	11
Eye pruritus	3/42 (7.1%)	3	1/87 (1.1%)	1
Eyelid ptosis	1/42 (2.4%)	1	5/87 (5.7%)	5
Foreign body sensation in eyes	2/42 (4.8%)	2	8/87 (9.2%)	8
Iridocyclitis	6/42 (14.3%)	6	1/87 (1.1%)	1
Macular fibrosis	5/42 (11.9%)	5	5/87 (5.7%)	5
Macular oedema	16/42 (38.1%)	16	6/87 (6.9%)	6
Ocular discomfort	1/42 (2.4%)	1	5/87 (5.7%)	5
Ocular hyperaemia	5/42 (11.9%)	5	7/87 (8%)	7
Photopsia	3/42 (7.1%)	3	5/87 (5.7%)	5
Posterior capsule opacification	3/42 (7.1%)	3	5/87 (5.7%)	5
Uveitis	26/42 (61.9%)	26	18/87 (20.7%)	18
Vision blurred	3/42 (7.1%)	3	2/87 (2.3%)	2
Visual acuity reduced	5/42 (11.9%)	5	16/87 (18.4%)	16
Visual impairment	3/42 (7.1%)	3	8/87 (9.2%)	8
Vitreous floaters	5/42 (11.9%)	5	8/87 (9.2%)	8
Vitreous opacities	4/42 (9.5%)	4	2/87 (2.3%)	2
Gastrointestinal disorders
Nausea	4/42 (9.5%)	4	3/87 (3.4%)	3
General disorders
Fatigue	3/42 (7.1%)	3	0/87 (0%)	0
Pain	3/42 (7.1%)	3	2/87 (2.3%)	2
Infections and infestations
Nasopharyngitis	5/42 (11.9%)	5	12/87 (13.8%)	12
Viral upper respiratory tract infection	3/42 (7.1%)	3	2/87 (2.3%)	2
Conjunctivitis	3/42 (7.1%)	3	2/87 (2.3%)	2
Investigations
Intraocular pressure increased	13/42 (31%)	13	28/87 (32.2%)	28
Nervous system disorders
Headache	3/42 (7.1%)	3	6/87 (6.9%)	6
Psychiatric disorders
Depression	1/42 (2.4%)	1	5/87 (5.7%)	5
Respiratory, thoracic and mediastinal disorders
Cough	4/42 (9.5%)	4	1/87 (1.1%)	1
Vascular disorders
Hypertension	4/42 (9.5%)	4	6/87 (6.9%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.