MkII: Utilization and Safety of the Mk II Inserter and the Safety of the FAI Insert in Non-Infectious Uveitis

• Sponsor: EyePoint Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02748512
• Collaborator: (none)
• Enrollment: 26
• Locations: 6
• Arms: 2
• Actual Duration (Months): 17.8
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This trial is a 12 month, Phase 3, multi-center, randomized, single-masked (subject), controlled study designed to evaluate the utilization and safety of the Mk II inserter and the safety of the FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye.

Condition or Disease	Intervention/Treatment	Phase
Non-Infectious Uveitis	Drug: FAI Insert administered using the Mk II inserter; Drug: FAI Insert administered using the Mk I inserter	Phase 3

Detailed Description

This trial is a 12 month, Phase 3, multi-center, randomized, single-masked (subject), controlled study designed to evaluate the utilization and safety of the MK II inserter and the safety of the FAI insert, in subjects with non-infectious uveitis affecting the posterior segment of the eye.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Controlled, Multi-Center Study of the Utilization and Safety of the MkII Inserter and the Safety of the FAI Insert in Subjects With Non-Infectious Uveitis Affecting the Posterior Segment of the Eye.
• Actual Study Start Date: Feb 23, 2016
• Actual Primary Completion Date: Aug 17, 2017
• Actual Study Completion Date: Aug 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FAI Insert administered using the Mk II inserter The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana.	Drug: FAI Insert administered using the Mk II inserter; Other Names: Fluocinolone Acetonide Intravitreal (FAI)
Active Comparator: FAI Insert administered using the Mk I inserter The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana.	Drug: FAI Insert administered using the Mk I inserter; Other Names: Fluocinolone Acetonide Intravitreal (FAI)

Outcome Measures

Primary Outcome Measures

1. The Utilization of the Mk II Inserter From the Day of Treatment Through 7 Days Following Treatment. [Day 7]

   The primary utilization endpoint was defined as the proportion of intravitreal insertion procedures that were assessed by the investigator as satisfactory. A satisfactory procedure was defined as one receiving a score from the Investigator as either Very Easy, Easy, or Routine.

Secondary Outcome Measures

1. The Safety of the FAI Insert During 12 Months Following Treatment Reported as Percentages. [Month 12]

   To assess the safety of the FAI insert during 12 months following treatment reported as percentages.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

2. At least one eye has a history of non-infectious uveitis affecting the posterior segment

3. Subject has ability to understand and sign the Informed Consent Form

4. Subject is willing and able to comply with study requirements

Exclusion Criteria:

1. Allergy to fluocinolone acetonide or any component of the FAI insert

2. Ocular malignancy in either eye, including choroidal melanoma

3. Uveitis with infectious etiology

4. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella

5. Current mycobacterial infections of the eye or fungal diseases of ocular structures

6. Subjects who yield, during screening, a confirmed positive test for human immune deficiency virus (HIV) or syphilis

7. Systemic infection within 30 days prior to study Day 1

8. Peripheral retinal detachment in area of insertion

9. Elevated intraocular pressure (IOP) > 21 mmHg, or chronic hypotony < 6 mmHg

10. Concurrent therapy at screening with IOP-lowering pharmacologic agent in the study eye

11. Current 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)

12. Known history of clinically significant IOP elevation in response to steroid treatment in either eye, 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)

13. Ocular surgery or capsulotomy performed on the study eye within 30 days prior to study Day 1

14. Intravitreal treatment of study eye: with FAI insert within 36 months prior to study Day 1;with Retisert within 30 months prior to study Day 1; with Ozurdex within 90 days prior to study Day 1; or with Triesence or Trivaris within 30 days prior to study Day 1

15. Peri-ocular or subtenon steroid treatment of study eye within 30 days prior to study Day 1

16. Treatment with an investigational drug or device within 30 days prior to study Day 1, except the FAI insert within this protocol

17. 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

18. Any condition which, in the judgment of the Investigator, could make the subject inappropriate for entry into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Consultants of Southern Colorado, PC	Colorado Springs	Colorado	United States	80909
2	Massachusetts Eye Research and Surgery Institution / Ocular Immunology & Uveitis Foundation	Waltham	Massachusetts	United States	02451
3	Duke Eye Center	Durham	North Carolina	United States	27710
4	Cleveland Clinic Foundation Cole Eye Institute	Cleveland	Ohio	United States	44195
5	Charleston Neuroscience Institute	Ladson	South Carolina	United States	29456
6	Texas Retina Associates	Arlington	Texas	United States	76012

Sponsors and Collaborators

• EyePoint Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Flavio Leonin Jr., MD, pSivida Corp, Senior Manager, Clinical Affairs
• Study Chair: Gerard E Riedel, PhD, pSivida Corp, Vice President, Regulatory Affairs
• Study Director: Paul Ashton, PhD, pSivida Corp, Chief Executive Officer

Study Documents (Full-Text)

• Study Protocol - Apr 4, 2016
• Statistical Analysis Plan - Apr 12, 2016

More Information

Publications

None provided.

• Responsible Party: EyePoint Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02748512
• Other Study ID Numbers: PSV-FAI-006
• First Posted: Apr 22, 2016
• Last Update Posted: May 1, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Uveitis; Fluocinolone Acetonide

Study Results

Participant Flow

Recruitment Details	One subject was assigned to the Mk II; however, received treatment with the Mk I after attempted to use 2 different Mk II inserters without success and switched to the Mk I inserter. The data for this subject were included in the Mk II inserter treatment group for ITT population and in the Mk I inserter treatment group for the safety population
Pre-assignment Detail	Prior to analysis no Subjects were Excluded From the Utilization Analysis (i.e., completed Day 7). 1 MKI and 1 MKII eyes were lost to follow-up at Month 12.

Arm/Group Title	Mk II Inserter	Mk I Inserter
Arm/Group Description	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk II inserter	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk I inserter
Period Title: Overall Study
STARTED	14	12
COMPLETED	13	11
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	FAI Insert Administered Using the Mk II Inserter	FAI Insert Administered Using the Mk I Inserter	Total
Arm/Group Description	The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana. FAI Insert administered using the Mk II inserter	The test article is the Fluocinolone Acetonide Intravitreal (FAI) insert, which contains 0.18 mg FA and delivers FA into the vitreous humor for 36 months, at a nominal rate of approximately 0.2 μg FA/day. The FAI insert will be administered to the study eye as an intravitreal injection through the pars plana. FAI Insert administered using the Mk I inserter	Total of all reporting groups
Overall Participants	14	12	26
Overall Eyes	27	11	38
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.3 (11.82)	48.9 (11.19)	50.4 (12.12)
Sex: Female, Male (Eyes) [Count of Units]
Female	18	7	25
Male	9	4	13
Race/Ethnicity, Customized (Eyes) [Count of Units]
White	21	8	29
Black or African American	5	3	8
Asian	1	0	1
Region of Enrollment (Eyes) [Number]
United States	27	11	38
Overall Eyes Evaluated (Eyes) [Count of Units]
Count of Units [Eyes]	27	11	38

Outcome Measures

1. Primary Outcome

Title	The Utilization of the Mk II Inserter From the Day of Treatment Through 7 Days Following Treatment.
Description	The primary utilization endpoint was defined as the proportion of intravitreal insertion procedures that were assessed by the investigator as satisfactory. A satisfactory procedure was defined as one receiving a score from the Investigator as either Very Easy, Easy, or Routine.
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

Intent-to-treat population - Assessment Categories

Arm/Group Title	Mk II Inserter	Mk I Inserter
Arm/Group Description	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk II inserter	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk I inserter
Measure Participants	14	12
Measure Eyes	27	11
Very Easy	10	3
Easy	3	2
Routine	5	0
Difficult	7	4
Very Difficult	2	2

2. Secondary Outcome

Title	The Safety of the FAI Insert During 12 Months Following Treatment Reported as Percentages.
Description	To assess the safety of the FAI insert during 12 months following treatment reported as percentages.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Overall Summary of Treatment-Emergent Ocular Adverse Events at Month 12 (Safety Population). Note 27/11 (ITT Population) and 26/12 (Safety Population).

Arm/Group Title	Mk II Inserter	Mk I Inserter
Arm/Group Description	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk II inserter	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk I inserter
Measure Participants	14	12
Measure Eyes	26	12
TEAE	12	7
Serious TEAE	1	1
Treatment-related TEAE	10	4
Treatment-related serious TEAE	0	0
TEAE leading to FAI insert removal	0	1
TEAE leading to study discontinuation	0	0
AE leading to death	0	0

Adverse Events

Time Frame	Overall Summary of Treatment-Emergent Non-ocular and Ocular Adverse Events at Month 12 (Safety Population - MKII 26 eyes; MKI 12 eyes)
Adverse Event Reporting Description	Overall Summary of Treatment-Emergent Non-ocular and Ocular Adverse Events at Month 12 (Safety Population - MKII 26 eyes; MKI 12 eyes)
Arm/Group Title	Mk II Inserter		Mk I Inserter
Arm/Group Description	Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk II inserter		Fluocinolone Acetonide Intravitreal (FAI) Insert, administered using the Mk I inserter
All Cause Mortality
	Mk II Inserter		Mk I Inserter
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/12 (0%)
Serious Adverse Events
	Mk II Inserter		Mk I Inserter
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/14 (28.6%)		3/12 (25%)
Cardiac disorders
Tachycardia	1/14 (7.1%)		1/12 (8.3%)
Eye disorders
Retinal Detachment	0/14 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Pancreatitis	1/14 (7.1%)		1/12 (8.3%)
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus	1/14 (7.1%)		1/12 (8.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Neoplasm	1/14 (7.1%)		0/12 (0%)
Psychiatric disorders
Factitious Disorder	1/14 (7.1%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/14 (7.1%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Mk II Inserter		Mk I Inserter
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		11/12 (91.7%)
Endocrine disorders
Pituitary-dependent Cushing's syndrome	1/14 (7.1%)		1/12 (8.3%)
Eye disorders
Anterior chamber cell	0/14 (0%)		1/12 (8.3%)
Cataract	4/14 (28.6%)		1/12 (8.3%)
Computer vision syndrome	0/14 (0%)		1/12 (8.3%)
Conjunctival haemorrhage	2/14 (14.3%)		0/12 (0%)
Eye pain	0/14 (0%)		1/12 (8.3%)
Eye pruritus	1/14 (7.1%)		0/12 (0%)
Lacrimation increased	1/14 (7.1%)		0/12 (0%)
Macular fibrosis	1/14 (7.1%)		0/12 (0%)
Meibomianitis	1/14 (7.1%)		0/12 (0%)
Posterior capsule opacification	1/14 (7.1%)		0/12 (0%)
Retinal detachment	0/14 (0%)		1/12 (8.3%)
Retinal pigment epitheliopathy	1/14 (7.1%)		0/12 (0%)
Retinal vascular disorder	1/14 (7.1%)		0/12 (0%)
Subretinal fluid	0/14 (0%)		1/12 (8.3%)
Uveitis	1/14 (7.1%)		0/12 (0%)
Visual acuity reduced	4/14 (28.6%)		1/12 (8.3%)
Vitreous haze	1/14 (7.1%)		0/12 (0%)
Gastrointestinal disorders
Diarrhoea	1/14 (7.1%)		1/12 (8.3%)
Pancreatic cyst	1/14 (7.1%)		0/12 (0%)
Toothache	0/14 (0%)		1/12 (8.3%)
General disorders
Injection site pain	0/14 (0%)		1/12 (8.3%)
Infections and infestations
Bronchitis	1/14 (7.1%)		0/12 (0%)
Candida Infection	1/14 (7.1%)		1/12 (8.3%)
Cellulitis	0/14 (0%)		1/12 (8.3%)
Nasopharyngitis	1/14 (7.1%)		0/12 (0%)
Oral Herpes	1/14 (7.1%)		0/12 (0%)
Tooth Infection	0/14 (0%)		1/12 (8.3%)
Urinary Tract Infection	1/14 (7.1%)		0/12 (0%)
Investigations
Laboratory test abnormal	1/14 (7.1%)		0/12 (0%)
Intraocular pressure decreased	0/14 (0%)		1/12 (8.3%)
Intraocular pressure increased	2/14 (14.3%)		2/12 (16.7%)
Metabolism and nutrition disorders
Gout	1/14 (7.1%)		0/12 (0%)
Hypokalemia	1/14 (7.1%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Back pain	2/14 (14.3%)		2/12 (16.7%)
Product Issues
Device dislocation	1/14 (7.1%)		1/12 (8.3%)
Device failure	0/14 (0%)		1/12 (8.3%)
Psychiatric disorders
Factitious disorder	1/14 (7.1%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/14 (7.1%)		1/12 (8.3%)
Sleep apnoea syndrome	1/14 (7.1%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Rash	1/14 (7.1%)		1/12 (8.3%)
Vascular disorders
Hypertension	2/14 (14.3%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PI is restricted from publicly releasing results.