Sirolimus in Conjunction With Eylea vs Eylea Alone for Exudative AMD

• Sponsor: Maturi, Raj K., M.D., P.C. (Other)
• Overall Status: Completed
• CT.gov ID: NCT02732899
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 12.1
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

To determine safety and efficacy of intravitreal injections of Sirolimus with adjunct EYLEA in subjects with exudative age related macular degeneration (AMD) with persistent intraretinal or subretinal edema due to neovascular AMD despite previous intravitreal anti-vascular endothelial growth factor (antiVEGF) treatment.

Condition or Disease	Intervention/Treatment	Phase
Exudative Age Related Macular Degeneration	Drug: Sirolimus; Drug: EYLEA	Phase 2

Detailed Description

This study is a single-center, masked, randomized, 36 week study, designed to evaluate the safety and treatment efficacy of intravitreal Sirolimus with adjunct EYLEA® (aflibercept) in patients with persistent edema due to neovascular AMD versus EYLEA® (aflibercept) alone. Twenty (20) patients will be randomized to receive study medication in a 1:1 ratio. Study treatment will be administered by intravitreal injections. The sham injections given in the EYLEA® alone group are needleless and they are given in order to help preserve the masking of those subjects in that treatment group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Sirolimus in Conjunction With EYLEA® (Aflibercept) Versus EYLEA® Alone for Exudative AMD
• Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Mar 20, 2017
• Actual Study Completion Date: Apr 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32.	Drug: Sirolimus; Other Names: DE-109 ; Drug: EYLEA; Other Names: aflibercept
Active Comparator: Group 2 Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment	Drug: EYLEA; Other Names: aflibercept

Outcome Measures

Primary Outcome Measures

1. Change in Central Subfield Thickness on OCT From Baseline to Week 36 [baseline to week 36]

   the amount of change in intraretinal and subretinal fluid as measured by microns of central subfield thickness (CST) on Heidelberg Optical Coherence Tomography (OCT)

Secondary Outcome Measures

1. Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36 [baseline to week 36]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female patients, 50 years of age or older at baseline

2. Patient has completed/signed an informed consent prior to any study-related procedures and is able to follow study instructions and likely to complete all required visits.

• Ocular Inclusion Criteria (Study eye only):

1. BCVA 5 - 75 (20/800-20/30), inclusive, in study eye; if both eyes are eligible, the eye with the best potential visual improvement as determined by the investigator will be selected for treatment.

2. Presence of choroidal neovascularization secondary to AMD

3. At least 3 previous intravitreal anti-VEGF injections in the past 6 months

4. Injection of antiVEGF may be deferred for at least 4 weeks from randomization based on clinical assessment of AMD by the investigator.

5. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging -

Exclusion Criteria:

1. Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception.

2. History or current evidence of hypersensitivity to any components of the study medication or fluorescein, as assessed by the investigator.

3. Participation in any investigational drug or device study within 30 days prior to baseline

4. History or current evidence of a medical condition that may, in the opinion of the investigator, preclude the safe administration of study medication or affect the results of the study.

• Ocular Exclusion Criteria (Study eye only):

1. Decrease of greater than 150 microns in central subfield thickness as measured by OCT since the last intravitreal injection in the study eye

2. Aphakia

3. History of pars plana vitrectomy in the study eye

4. History of major ophthalmic surgery in the study eye in the past 3 months and any ophthalmic surgery in the study eye within the past 30 days

5. History of significant ocular disease or condition other than exudative AMD that may confound results

6. Uncontrolled glaucoma (defined as intraocular pressure >21mm Hg despite treatment with two or more ocular hypotensive medications at baseline)

7. No active ocular or periocular infections, or ocular malignancy including lymphoma

8. Presence of significant epiretinal membrane

9. Significant vitreoretinal traction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Raj K Maturi MD PC	Indianapolis	Indiana	United States	46290

Sponsors and Collaborators

• Maturi, Raj K., M.D., P.C.

Investigators

• Principal Investigator: Raj K Maturi, MD, Raj K. Maturi, MD, PC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 11, 2016

More Information

Publications

None provided.

• Responsible Party: Maturi, Raj K., M.D., P.C.
• ClinicalTrials.gov Identifier: NCT02732899
• Other Study ID Numbers: RKM009
• First Posted: Apr 11, 2016
• Last Update Posted: Feb 14, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Maturi, Raj K., M.D., P.C.: AMD
• Additional relevant MeSH terms: Macular Degeneration; Sirolimus; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. Sirolimus EYLEA	Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment EYLEA
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Total
Arm/Group Description	Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. Sirolimus EYLEA	Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment EYLEA	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71	77	74
Sex: Female, Male (Count of Participants)
Female	6 60%	8 80%	14 70%
Male	4 40%	2 20%	6 30%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	10 100%	10 100%	20 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Central Subfield Thickness on OCT From Baseline to Week 36
Description	the amount of change in intraretinal and subretinal fluid as measured by microns of central subfield thickness (CST) on Heidelberg Optical Coherence Tomography (OCT)
Time Frame	baseline to week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. Sirolimus EYLEA	Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment EYLEA
Measure Participants	10	10
Mean (Full Range) [microns]	-54	-.1

2. Secondary Outcome

Title	Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36
Time Frame	baseline to week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. Sirolimus EYLEA	Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment EYLEA
Measure Participants	10	10
Mean (Full Range) [letters]	2.5	0.8

Adverse Events

Time Frame	6 months
Arm/Group Title	Group 1		Group 2
Arm/Group Description	Sirolimus 440ug for intravitreal injection will be provided in sterile single-use glass vials. One single-dose vial will be packaged in a box for each patient injection. Sirolimus injections will be given at baseline, week 4, 12, 20 and 28. EYLEA® (aflibercept) intravitreal injections will be given at week 1, 8, 16, 24 and 32. Sirolimus EYLEA		Intravitreal injection of EYLEA® (aflibercept) will be given at baseline, week 8, 16, 24 and 32. Sham injections will be given at week 1, 4, 12, 20, and 28 in order to maintain masking of patient to treatment assignment EYLEA
All Cause Mortality
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		0/10 (0%)
Gastrointestinal disorders
pancreatitis	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
pneumonia	1/10 (10%)	1	0/10 (0%)	0
Vascular disorders
worsening hypertension	1/10 (10%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		5/10 (50%)
Blood and lymphatic system disorders
anemia	0/10 (0%)	0	1/10 (10%)	1
Eye disorders
worsening subretinal hemorrhage	0/10 (0%)	0	1/10 (10%)	1
progressed posterior capsule opacification	2/10 (20%)	2	0/10 (0%)	0
dot hemorrhage on retina	2/10 (20%)	2	0/10 (0%)	0
progressed nuclear sclerotic cataract	1/10 (10%)	1	0/10 (0%)	0
subretinal hemorrhage	0/10 (0%)	0	1/10 (10%)	1
hyperemia	2/10 (20%)	2	0/10 (0%)	0
increased metemorphopsia	2/10 (20%)	3	0/10 (0%)	0
foreign body sensation	1/10 (10%)	1	0/10 (0%)	0
eye pain	1/10 (10%)	2	1/10 (10%)	1
chalazion	0/10 (0%)	0	1/10 (10%)	1
epiphora	0/10 (0%)	0	1/10 (10%)	1
eyelid edema	1/10 (10%)	1	1/10 (10%)	1
Gastrointestinal disorders
abdominal pain	0/10 (0%)	0	1/10 (10%)	1
General disorders
combigan allergy	1/10 (10%)	1	0/10 (0%)	0
Infections and infestations
sinusitis	1/10 (10%)	1	0/10 (0%)	0
tooth infection	1/10 (10%)	1	0/10 (0%)	0
Renal and urinary disorders
urinary tract infection	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
bronchitis	3/10 (30%)	4	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.