Safety and Efficacy Study of a FAI Insert in Subjects With Chronic Non-infectious Posterior Uveitis

• Sponsor: EyePoint Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02746991
• Collaborator: (none)
• Enrollment: 153
• Locations: 15
• Arms: 2
• Actual Duration (Months): 52.1
• Patients Per Site: 10.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Phase 3, 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 chronic 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.

Condition or Disease	Intervention/Treatment	Phase
Posterior Uveitis; Intermediate Uveitis; Panuveitis	Drug: Sham Injection; Drug: FAI Insert	Phase 3

Detailed Description

This is a phase 3, 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 chronic 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: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Controlled, Safety and Efficacy Study of a Fluocinolone Acetonide Intravitreal (FAI) Insert in Subjects With Chronic Non-infectious Uveitis Affecting the Posterior Segment of the Eye
• Actual Study Start Date: Jun 2, 2015
• Actual Primary Completion Date: Oct 4, 2019
• Actual Study Completion Date: Oct 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham Injection Sham Injection	Drug: Sham Injection; Placebo; Other Names: Placebo
Experimental: FAI Insert FAI Insert (0.18 mg fluocinolone acetonide)	Drug: FAI Insert; Fluocinolone Acetonide; Other Names: Fluocinolone Acetonide

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Recurrence of Uveitis in Study Eye Within 6 Months [6 Months]

   Proportion of Subjects with Recurrence of Uveitis in the Study Eye within 6 Months Including Reason for Imputed Recurrence (ITT Population)

Secondary Outcome Measures

1. Number of Participants With Recurrence of Uveitis in Study Eye Within 36 Months [36 Months]

   Proportion of Subjects with Recurrence of Uveitis in the Study Eye at 36 Months Including Reason for Imputed Recurrence (ITT Population)

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

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

• Visual acuity of study eye is at least 15 letters on the Early Treatment Diabetic Retinopathy Study (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

• 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 administrations 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

Exclusion Criteria:

• Allergy to fluocinolone acetonide or any component of the Fluocinolone Acetonide Intravitreal (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 structures

• 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 Intraocular pressure (IOP) in the normal range (10-21 mmHg)

• 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 have tested positive for human immune deficiency virus (HIV), tuberculosis or syphilis

• 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	LV. Prasad Eye Institute	Hyderabad	Andhra Pradesh	India	500034
2	Sri Sankaradeva Nethralaya, Guwahati	Guwahati	Assam	India	781028
3	Regional Institute of Opthalmology	Patna	Bihar	India	800014
4	C.H. Nagri Municipal Eye Hospital	Ahmedabad	Gujarat	India	380006
5	Seth G.S. Medical College & K.E.M Hospital	Mumbai	Maharashtra	India	400012
6	Deenanath Mangeshkar Hospital, Pune	Pune	Maharashtra	India	411004
7	PBMA'S, H. V. Desai Eye Hospital	Pune	Maharashtra	India	411060
8	Dr. Shroff's Charity Eye Hospital	Daryaganj	New Delhi	India	110002
9	Sankara Nethralaya hospital	Chennai	Tamil Nadu	India	600006
10	Vasan Eye Care Hospital	Chennai	Tamil Nadu	India	600015
11	Sri Ramachandra Hospital	Chennai	Tamil Nadu	India	600116
12	J L Rohatgi Memorial Eye Hospital	Kanpur	Uttar Pradesh	India	208005
13	King George's Medical University	Lucknow	Uttar Pradesh	India	226003
14	ICARE Eye Hospital and Research centre	Noida	Uttar Pradesh	India	201301
15	Regional Institute of Ophthalmology	Kolkata	West Bengal	India	700073

Sponsors and Collaborators

• EyePoint Pharmaceuticals, Inc.

Investigators

• Study Director: Flavio Leonin Jr., MD, EyePoint Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 10, 2017
• Statistical Analysis Plan - Mar 10, 2017

More Information

Publications

None provided.

• Responsible Party: EyePoint Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02746991
• Other Study ID Numbers: PSV-FAI-005
• First Posted: Apr 21, 2016
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Uveitis; Panuveitis; Uveitis, Posterior; Uveitis, Intermediate; Pars Planitis; Fluocinolone Acetonide

Study Results

Participant Flow

Arm/Group Title	Sham Injection	FAI Insert
Arm/Group Description	Placebo Injection	Fluocinolone Acetonide Intravitreal (FAI) Insert Group
Period Title: Overall Study
STARTED	52	101
COMPLETED	24	67
NOT COMPLETED	28	34

Baseline Characteristics

Arm/Group Title	Sham Injection	FAI Insert	Total
Arm/Group Description	Placebo Injection	FAI Insert Group	Total of all reporting groups
Overall Participants	52	101	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.6 (13.74)	39.9 (12.87)	40.1 (13.13)
Age, Customized (Count of Participants)
<20 years	2 3.8%	0 0%	2 1.3%
20 to <40 years	25 48.1%	57 56.4%	82 53.6%
40 to <60 years	21 40.4%	34 33.7%	55 35.9%
>=60 years	4 7.7%	10 9.9%	14 9.2%
Sex: Female, Male (Count of Participants)
Female	34 65.4%	62 61.4%	96 62.7%
Male	18 34.6%	39 38.6%	57 37.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	52 100%	101 100%	153 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	49 94.2%	96 95%	145 94.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 5.8%	5 5%	8 5.2%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Intention To Treat (ITT) Population (Count of Participants)
Count of Participants [Participants]	52 100%	101 100%	153 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Recurrence of Uveitis in Study Eye Within 6 Months
Description	Proportion of Subjects with Recurrence of Uveitis in the Study Eye within 6 Months Including Reason for Imputed Recurrence (ITT Population)
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Proportion of Subjects with Recurrence of Uveitis in the Study Eye within 6 Months Including Reason for Imputed Recurrence (ITT Population)

Arm/Group Title	Sham Injection	FAI Insert
Arm/Group Description	Placebo Injection	FAI Insert Group
Measure Participants	52	101
Count of Participants [Participants]	28 53.8%	22 21.8%

2. Secondary Outcome

Title	Number of Participants With Recurrence of Uveitis in Study Eye Within 36 Months
Description	Proportion of Subjects with Recurrence of Uveitis in the Study Eye at 36 Months Including Reason for Imputed Recurrence (ITT Population)
Time Frame	36 Months

Outcome Measure Data

Analysis Population Description

Proportion of Subjects with Recurrence of Uveitis in the Study Eye at 36 Months Including Reason for Imputed Recurrence (ITT Population)

Arm/Group Title	Sham Injection	FAI Insert
Arm/Group Description	Sham Injection Sham Injection: Placebo	FAI Insert (0.18 mg fluocinolone acetonide) FAI Insert: Fluocinolone Acetonide
Measure Participants	52	101
Count of Participants [Participants]	39 75%	47 46.5%

Adverse Events

Time Frame	36 months. All Adverse Event (AE)s will be evaluated from their onset until resolution, stabilization, last day of participation in the study of the patient or the last day of the study, whichever is first.
Adverse Event Reporting Description	Treatment-Emergent Ocular Adverse Events through Month 36 Visit by Eye, System Organ Class, and Preferred Term in More than 5% of Subjects in Either Treatment Group (Safety Population)
Arm/Group Title	Sham Injection		FAI Insert
Arm/Group Description	Placebo Injection		FAI Insert Group
All Cause Mortality
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/101 (0%)
Serious Adverse Events
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/52 (13.5%)		21/101 (20.8%)
Eye disorders
Cataract	0/52 (0%)		2/101 (2%)
Choroiditis	0/52 (0%)		1/101 (1%)
Glaucoma	0/52 (0%)		2/101 (2%)
Hypotony of eye	0/52 (0%)		8/101 (7.9%)
Optic atrophy	0/52 (0%)		1/101 (1%)
Optic ischaemic neuropathy	0/52 (0%)		1/101 (1%)
Retinal detachment	0/52 (0%)		1/101 (1%)
Vitreous haemorrhage	0/52 (0%)		1/101 (1%)
Vitreous haze	0/52 (0%)		1/101 (1%)
Infections and infestations
Sepsis	1/52 (1.9%)		0/101 (0%)
Septic Shock	1/52 (1.9%)		0/101 (0%)
Tuberculosis Gastrointestinal	1/52 (1.9%)		0/101 (0%)
Injury, poisoning and procedural complications
Post procedural complication	0/52 (0%)		1/101 (1%)
Investigations
Uveitis	1/52 (1.9%)		1/101 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/52 (1.9%)		0/101 (0%)
Rectal Cancer	1/52 (1.9%)		0/101 (0%)
Tongue Neoplasm Malignant Stage Unspecified	0/52 (0%)		1/101 (1%)
Renal and urinary disorders
Acute Kidney Injury	1/52 (1.9%)		0/101 (0%)
Other (Not Including Serious) Adverse Events
	Sham Injection		FAI Insert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/52 (94.2%)		94/101 (93.1%)
Cardiac disorders
Palpitations	0/52 (0%)		1/101 (1%)
Ear and labyrinth disorders
Otorrhoea	0/52 (0%)		1/101 (1%)
Vertigo	0/52 (0%)		1/101 (1%)
Endocrine disorders
Hyperprolactinaemia	1/52 (1.9%)		0/101 (0%)
Hypopituitarism	1/52 (1.9%)		0/101 (0%)
Eye disorders
Anterior chamber cell	7/52 (13.5%)		10/101 (9.9%)
Cataract	10/52 (19.2%)		17/101 (16.8%)
Cataract subcapsular	9/52 (17.3%)		36/101 (35.6%)
Conjunctival haemorrhage	1/52 (1.9%)		6/101 (5.9%)
Cystoid macular oedema	8/52 (15.4%)		4/101 (4%)
Dry eye	2/52 (3.8%)		5/101 (5%)
Eye pain	8/52 (15.4%)		6/101 (5.9%)
Eye pruritus	6/52 (11.5%)		4/101 (4%)
Glaucoma	1/52 (1.9%)		5/101 (5%)
Hypotony of eye	0/52 (0%)		10/101 (9.9%)
Iris adhesions	4/52 (7.7%)		2/101 (2%)
Macular fibrosis	0/52 (0%)		7/101 (6.9%)
Macular oedema	11/52 (21.2%)		9/101 (8.9%)
Ocular hyperaemia	4/52 (7.7%)		2/101 (2%)
Posterior capsule opacification	5/52 (9.6%)		9/101 (8.9%)
Uveitis	27/52 (51.9%)		20/101 (19.8%)
Visual acuity reduced	4/52 (7.7%)		15/101 (14.9%)
Vitreous haze	9/52 (17.3%)		12/101 (11.9%)
Vitritis	10/52 (19.2%)		9/101 (8.9%)
Gastrointestinal disorders
Abdominal pain	1/52 (1.9%)		0/101 (0%)
Abdominal pain upper	0/52 (0%)		1/101 (1%)
Diarrhoea	0/52 (0%)		1/101 (1%)
Nausea	1/52 (1.9%)		0/101 (0%)
General disorders
Asthenia	1/52 (1.9%)		0/101 (0%)
Generalised oedema	0/52 (0%)		1/101 (1%)
Non-cardiac chest pain	0/52 (0%)		1/101 (1%)
Pyrexia	2/52 (3.8%)		2/101 (2%)
Infections and infestations
Conjunctivitis	4/52 (7.7%)		4/101 (4%)
Furuncle	0/52 (0%)		1/101 (1%)
Hepatitis B	1/52 (1.9%)		0/101 (0%)
Malaria	0/52 (0%)		1/101 (1%)
Pneumonia	1/52 (1.9%)		1/101 (1%)
Sepsis	1/52 (1.9%)		0/101 (0%)
Septic shock	1/52 (1.9%)		0/101 (0%)
Tuberculosis gastrointestinal	1/52 (1.9%)		0/101 (0%)
Typhoid fever	1/52 (1.9%)		0/101 (0%)
Urinary tract infection	1/52 (1.9%)		0/101 (0%)
Viral infection	1/52 (1.9%)		0/101 (0%)
Injury, poisoning and procedural complications
Muscle strain	0/52 (0%)		1/101 (1%)
Investigations
Intraocular pressure increased	2/52 (3.8%)		32/101 (31.7%)
Blood cholesterol increased	0/52 (0%)		1/101 (1%)
Metabolism and nutrition disorders
Decreased appetite	1/52 (1.9%)		0/101 (0%)
Diabetes mellitus	1/52 (1.9%)		2/101 (2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/52 (0%)		1/101 (1%)
Back pain	1/52 (1.9%)		0/101 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/52 (1.9%)		0/101 (0%)
Rectal Cancer	1/52 (1.9%)		0/101 (0%)
Rectal cancer metastatic	1/52 (1.9%)		0/101 (0%)
Tongue neoplasm malignant stage unspecified	0/52 (0%)		1/101 (1%)
Nervous system disorders
Dizziness	1/52 (1.9%)		0/101 (0%)
Headache	1/52 (1.9%)		1/101 (1%)
Parkinsonism	0/52 (0%)		1/101 (1%)
Psychiatric disorders
Mood swings	0/52 (0%)		1/101 (1%)
Renal and urinary disorders
Acute kidney injury	1/52 (1.9%)		0/101 (0%)
Reproductive system and breast disorders
Breast discharge	1/52 (1.9%)		0/101 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/52 (1.9%)		1/101 (1%)
Dyspnoea exertional	0/52 (0%)		1/101 (1%)
Oropharyngeal pain	1/52 (1.9%)		0/101 (0%)
Respiratory distress	1/52 (1.9%)		0/101 (0%)
Rhinitis allergic	1/52 (1.9%)		0/101 (0%)
Skin and subcutaneous tissue disorders
Acne	0/52 (0%)		1/101 (1%)
Hyperhidrosis	0/52 (0%)		2/101 (2%)
Pruritus	0/52 (0%)		2/101 (2%)
Rash	0/52 (0%)		1/101 (1%)
Vascular disorders
Hypertension	2/52 (3.8%)		5/101 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.