Study Assessing the Efficacy and Safety of Intravitreal Injections of DE-122 in Combination With Lucentis® Compared to Lucentis® Monotherapy in Wet Age-related Macular Degeneration Subjects

• Sponsor: Santen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03211234
• Collaborator: (none)
• Enrollment: 76
• Locations: 14
• Arms: 3
• Actual Duration (Months): 30.9
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the safety and efficacy of repeated intravitreal injections of DE-122 (low dose and high dose) given in combination with Lucentis® in subjects with wet age-related macular degeneration (AMD) compared with Lucentis® alone.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: 2.0 mg DE-122 Injectable Solution + Lucentis; Drug: 4.0 mg DE-122 Injectable Solution + Lucentis; Drug: Lucentis	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Double Masked and Active Controlled Phase II Study Assessing the Efficacy and Safety of Intravitreal Injections of DE-122 in Combination With Lucentis® Compared to Lucentis® Monotherapy in Subjects With Wet Age-related Macular Degeneration - AVANTE Study
• Actual Study Start Date: Jul 5, 2017
• Actual Primary Completion Date: Dec 31, 2019
• Actual Study Completion Date: Jan 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2.0 mg DE-122 2.0 mg DE-122 and Lucentis ® 0.5 mg	Drug: 2.0 mg DE-122 Injectable Solution + Lucentis; Subjects will receive 6 monthly intravitreal injections of low dose DE-122 in the study eye, in combination with Lucentis.
Experimental: 4.0 mg DE-122 4.0 mg DE-122 and Lucentis ® 0.5 mg	Drug: 4.0 mg DE-122 Injectable Solution + Lucentis; Subjects will receive 6 monthly intravitreal injections of high dose DE-122 in the study eye, in combination with Lucentis.
Sham Comparator: Sham Sham and Lucentis ® 0.5 mg	Drug: Lucentis; Subjects will receive 6 monthly intravitreal injections of Sham in the study eye, in combination with Lucentis.

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 24 [Week 24]

   BCVA is the primary efficacy variable for this study, and mean change from baseline in BCVA at Week 24 is the primary efficacy endpoint. An increase in the number of letters read correctly means that vision has improved.The lower the number of letters read correctly on the eye chart, the worse the vision.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provide signed written informed consent

• Diagnosis of active choroidal neovascularization secondary to wet AMD

• BCVA of 65 to 25 ETDRS letters (20/50 to 20/320) in the study eye

• BCVA of 25 ETDRS letters (20/320) or better in the fellow eye

Exclusion Criteria:

[Ocular]

• Use or anticipated use of any intravitreal, periocular or photodynamic therapy in the study eye for the treatment of AMD within a specified timeframe prior to Visit 1 and throughout the study

• Uncontrolled or advanced glaucoma, chronic hypotony or vitrectomy in the study eye

• Evidence of any other ocular disease other than exudative age-related macular degeneration in the study eye that may confound the outcome of the study

• Need for ocular surgery in the study eye during the course of the study

• Presence or history of certain ocular or periocular pathology or conditions that could limit the ability to perform examinations

[Non-ocular]

• Allergy or hypersensitivity to study drug product, fluorescein dye or other study related procedures and medications

• Current or history of certain systemic conditions, abnormalities or therapies that would render a subject a poor candidate for the study

• Participation in other investigational drug or device clinical trials within 30 days prior to randomization or planning to participate in other investigational drug or device clinical trials for the duration of the study

• Females who are pregnant or lactating and females of child-bearing potential who are not using adequate contraceptive precautions and men who do not agree to practice an acceptable method of contraception throughout the course of the study

• Unable to comply with study procedures or follow-up visits

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Research Institute	Gilbert	Arizona	United States	85296
2	Retina-Vitreous Associates	Beverly Hills	California	United States	90211
3	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
4	Bay Area Retina Associates	Walnut Creek	California	United States	94598
5	Colorado Retina Associates	Golden	Colorado	United States	80401
6	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
7	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
8	Retina Reseach Center	Austin	Texas	United States	78705
9	Retina Consultants of Houston	Houston	Texas	United States	77030
10	Valley Retina Insititute	McAllen	Texas	United States	78503
11	Asian Eye Institute	Makati City		Philippines
12	Peregrine Eye and Laser Institute	Makati City		Philippines
13	The Medical City	Pasig City		Philippines
14	St. Luke's Medical center Quezon City	Quezon City		Philippines

Sponsors and Collaborators

• Santen Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 8, 2019
• Statistical Analysis Plan - Oct 11, 2019

More Information

Publications

None provided.

• Responsible Party: Santen Inc.
• ClinicalTrials.gov Identifier: NCT03211234
• Other Study ID Numbers: 36-002
• First Posted: Jul 7, 2017
• Last Update Posted: Jul 13, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Sham	2.0 mg DE-122	4.0 mg DE-122
Arm/Group Description	Sham and Lucentis Lucentis: Subjects will receive 6 monthly intravitreal injections of Sham in the study eye, in combination with Lucentis.	Low Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of low dose DE-122 in the study eye, in combination with Lucentis.	High Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of high dose DE-122 in the study eye, in combination with Lucentis.
Period Title: Overall Study
STARTED	17	31	28
COMPLETED	16	30	25
NOT COMPLETED	1	1	3

Baseline Characteristics

Arm/Group Title	Sham	2.0 mg DE-122	4.0 mg DE-122	Total
Arm/Group Description	Sham and Lucentis Lucentis: Subjects will receive 6 monthly intravitreal injections of Sham in the study eye, in combination with Lucentis.	Low Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of low dose DE-122 in the study eye, in combination with Lucentis.	High Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of high dose DE-122 in the study eye, in combination with Lucentis.	Total of all reporting groups
Overall Participants	17	31	28	76
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.4 (9.18)	72.1 (7.34)	75.6 (9.84)	74.1 (8.79)
Sex: Female, Male (Count of Participants)
Female	12 70.6%	14 45.2%	15 53.6%	41 53.9%
Male	5 29.4%	17 54.8%	13 46.4%	35 46.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	9 52.9%	9 29%	4 14.3%	22 28.9%
Native Hawaiian or Other Pacific Islander	0 0%	1 3.2%	0 0%	1 1.3%
Black or African American	0 0%	1 3.2%	0 0%	1 1.3%
White	8 47.1%	20 64.5%	24 85.7%	52 68.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 52.9%	22 71%	25 89.3%	56 73.7%
Philippines	8 47.1%	9 29%	3 10.7%	20 26.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 24
Description	BCVA is the primary efficacy variable for this study, and mean change from baseline in BCVA at Week 24 is the primary efficacy endpoint. An increase in the number of letters read correctly means that vision has improved.The lower the number of letters read correctly on the eye chart, the worse the vision.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham	2.0 mg DE-122	4.0 mg DE-122
Arm/Group Description	Sham and Lucentis Lucentis: Subjects will receive 6 monthly intravitreal injections of Sham in the study eye, in combination with Lucentis.	Low Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of low dose DE-122 in the study eye, in combination with Lucentis.	High Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of high dose DE-122 in the study eye, in combination with Lucentis.
Measure Participants	17	31	28
Mean (Standard Deviation) [letters]	4.35 (8.937)	0.87 (11.485)	-1.70 (10.550)

Adverse Events

Time Frame	From Inform consent to the end of the study at week 32.
Arm/Group Title	Sham		2.0 mg DE-122		4.0 mg DE-122
Arm/Group Description	Sham and Lucentis Lucentis: Subjects will receive 6 monthly intravitreal injections of Sham in the study eye, in combination with Lucentis.		Low Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of low dose DE-122 in the study eye, in combination with Lucentis.		High Dose DE-122 and Lucentis DE-122 Injectable Solution + Lucentis: Subjects will receive 6 monthly intravitreal injections of high dose DE-122 in the study eye, in combination with Lucentis.
All Cause Mortality
	Sham		2.0 mg DE-122		4.0 mg DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/31 (0%)		1/28 (3.6%)
Serious Adverse Events
	Sham		2.0 mg DE-122		4.0 mg DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		1/31 (3.2%)		4/28 (14.3%)
Cardiac disorders
Cardiac arrest	0/17 (0%)		0/31 (0%)		1/28 (3.6%)
Eye disorders
Cataract	0/17 (0%)		1/31 (3.2%)		0/28 (0%)
Subretinal fluid	0/17 (0%)		0/31 (0%)		1/28 (3.6%)
Infections and infestations
Pneumonia	1/17 (5.9%)		1/31 (3.2%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/17 (0%)		0/31 (0%)		1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/17 (0%)		0/31 (0%)		1/28 (3.6%)
Other (Not Including Serious) Adverse Events
	Sham		2.0 mg DE-122		4.0 mg DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)		10/31 (32.3%)		10/28 (35.7%)
Eye disorders
Conjunctival hyperaemia	0/17 (0%)		2/31 (6.5%)		4/28 (14.3%)
Eye pain	0/17 (0%)		4/31 (12.9%)		1/28 (3.6%)
Conjunctival haemorrhage	2/17 (11.8%)		3/31 (9.7%)		0/28 (0%)
Conjunctival oedema	0/17 (0%)		1/31 (3.2%)		2/28 (7.1%)
Erythema of eyelid	0/17 (0%)		1/31 (3.2%)		2/28 (7.1%)
Retinal haemorrhage	0/17 (0%)		3/31 (9.7%)		3/28 (10.7%)
Eyelid oedema	0/17 (0%)		1/31 (3.2%)		3/28 (10.7%)
Visual impairment	0/17 (0%)		1/31 (3.2%)		2/28 (7.1%)
Dry Eye	0/17 (0%)		2/31 (6.5%)		0/28 (0%)
Vitreous hemorrhage	0/17 (0%)		2/31 (6.5%)		0/28 (0%)
General disorders
Pyrexia	1/17 (5.9%)		0/31 (0%)		0/28 (0%)
Infections and infestations
Viral upper respiratory tract infection	1/17 (5.9%)		0/31 (0%)		1/28 (3.6%)
Investigations
Intraocular pressure increased	0/17 (0%)		2/31 (6.5%)		1/28 (3.6%)
Alanine aminotransferase increased	1/17 (5.9%)		0/31 (0%)		0/28 (0%)
Aspartate aminotransferase increased	1/17 (5.9%)		0/31 (0%)		0/28 (0%)
Nervous system disorders
Headache	0/17 (0%)		0/31 (0%)		2/28 (7.1%)
Presyncope	1/17 (5.9%)		0/31 (0%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/17 (5.9%)		0/31 (0%)		0/28 (0%)
Skin and subcutaneous tissue disorders
Rash	1/17 (5.9%)		0/31 (0%)		0/28 (0%)

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.