PAVE: A Phase I/II Safety, Tolerability, Immunogenicity, and Bioactivity Study of DE-122 Injectable Solution for Refractory Exudative Age-related Macular Degeneration

• Sponsor: Santen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02555306
• Collaborator: (none)
• Enrollment: 12
• Locations: 5
• Arms: 4
• Actual Duration (Months): 22.5
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, immunogenicity, and bioactivity of a single intravitreal (IVT) administration of DE-122 in subjects with refractory exudative age-related macular degeneration (AMD).

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: 0.5 mg of DE-122; Drug: 1.0 mg of DE-122; Drug: 2.0 mg of DE-122; Drug: 4.0 mg of DE-122	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label, Dose-escalating, Sequential-cohort Study Assessing the Safety, Tolerability, Immunogenicity, and Bioactivity of a Single Intravitreal Injection of DE-122 Injectable Solution for the Treatment of Refractory Exudative Age-related Macular Degeneration
• Actual Study Start Date: Sep 16, 2015
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low Dose DE-122 Single intravitreal injection of DE-122 Low Dose Injectable Solution	Drug: 0.5 mg of DE-122; DE-122 Injectable Solution
Experimental: Medium-Low Dose DE-122 Single intravitreal injection of DE-122 Medium-Low Dose Injectable Solution	Drug: 1.0 mg of DE-122; DE-122 Injectable Solution
Experimental: Medium-High Dose DE-122 Single intravitreal injection of DE-122 Medium-High Dose Injectable Solution	Drug: 2.0 mg of DE-122; DE-122 Injectable Solution
Experimental: High Dose DE-122 Single intravitreal injection of DE-122 High Dose Injectable Solution	Drug: 4.0 mg of DE-122; DE-122 Injectable Solution

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best Corrected Visual Acuity (BCVA) at Day 90. [Baseline (Day1) and Day 90.]

   BCVA measures the acuteness or clearness of best-corrected vision in ETDRS (Early Treatment of Diabetic Retinopathy Study) letters, with a range of [0, 97] in ETDRS letters. An increase in BCVA indicates an improvement in the best corrected vision.

Secondary Outcome Measures

1. Change From Baseline in Central Subfield Thickness (CST) at Day 90. [Baseline (Day1) and Day 90.]

   Bioactivity measures include CST (μm) measured by SD-OCT. Bioactivity will be considered evident if a considerable decrease in CST is observed.

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 subretinal or intraretinal fluid secondary to exudative age-related macular degeneration

• Prior treatment in the study eye with any intravitreal anti-VEGF medication

• At least one lesion in the study eye that meets minimal pathology criteria

• Best corrected visual acuity of 65 to 20 ETDRS letters in the study eye

• Best corrected visual acuity of 20/200 or better in the fellow eye

• Reasonably clear media and some fixation in the study 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

• 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 required study assessments in either eye and/or confound study results

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		Mountain View	California	United States	94040
2		Walnut Creek	California	United States	94598
3		Jackson	Michigan	United States	49202
4		Austin	Texas	United States	78705
5		McAllen	Texas	United States	78503

Sponsors and Collaborators

• Santen Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 30, 2016
• Statistical Analysis Plan - Aug 9, 2017

More Information

Publications

None provided.

• Responsible Party: Santen Inc.
• ClinicalTrials.gov Identifier: NCT02555306
• Other Study ID Numbers: 36-001
• First Posted: Sep 21, 2015
• Last Update Posted: Jan 14, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Santen Inc.: Macular Degeneration
• Additional relevant MeSH terms: Macular Degeneration

Study Results

Participant Flow

Arm/Group Title	0.5 mg of DE-122	1.0 mg of DE-122	2.0 mg of DE-122	4.0 mg of DE-122
Arm/Group Description	Single intravitreal injection of Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-High Dose DE-122 Injectable Solution	Single intravitreal injection of High Dose DE-122 Injectable Solution
Period Title: Overall Study
STARTED	3	3	3	3
COMPLETED	3	3	3	3
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	0.5 mg of DE-122	1.0 mg of DE-122	2.0 mg of DE-122	4.0 mg of DE-122	Total
Arm/Group Description	Single intravitreal injection of Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-High Dose DE-122 Injectable Solution	Single intravitreal injection of High Dose DE-122 Injectable Solution	Total of all reporting groups
Overall Participants	3	3	3	3	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 33.3%	0 0%	0 0%	0 0%	1 8.3%
>=65 years	2 66.7%	3 100%	3 100%	3 100%	11 91.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.7 (4.2)	73.7 (1.2)	74.0 (6.2)	84.0 (7.2)	74.3 (8.1)
Sex: Female, Male (Count of Participants)
Female	3 100%	1 33.3%	1 33.3%	2 66.7%	7 58.3%
Male	0 0%	2 66.7%	2 66.7%	1 33.3%	5 41.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	3 100%	3 100%	2 66.7%	11 91.7%
More than one race	0 0%	0 0%	0 0%	1 33.3%	1 8.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) at Day 90.
Description	BCVA measures the acuteness or clearness of best-corrected vision in ETDRS (Early Treatment of Diabetic Retinopathy Study) letters, with a range of [0, 97] in ETDRS letters. An increase in BCVA indicates an improvement in the best corrected vision.
Time Frame	Baseline (Day1) and Day 90.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.5 mg of DE-122	1.0 mg of DE-122	2.0 mg of DE-122	4.0 mg of DE-122
Arm/Group Description	Single intravitreal injection of Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-High Dose DE-122 Injectable Solution	Single intravitreal injection of High Dose DE-122 Injectable Solution
Measure Participants	3	3	3	3
Mean (Standard Deviation) [ETDRS letters]	-1.3 (2.1)	2.7 (5.0)	1.0 (7.9)	3.3 (4.5)

2. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness (CST) at Day 90.
Description	Bioactivity measures include CST (μm) measured by SD-OCT. Bioactivity will be considered evident if a considerable decrease in CST is observed.
Time Frame	Baseline (Day1) and Day 90.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.5 mg of DE-122	1.0 mg of DE-122	2.0 mg of DE-122	4.0 mg of DE-122
Arm/Group Description	Single intravitreal injection of Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-Low Dose DE-122 Injectable Solution	Single intravitreal injection of Medium-High Dose DE-122 Injectable Solution	Single intravitreal injection of High Dose DE-122 Injectable Solution
Measure Participants	3	3	3	3
Mean (Standard Deviation) [microns]	-116.3 (194.9)	62.7 (68.1)	-36.0 (42.6)	-111.3 (171.2)

Adverse Events

Time Frame	From Visit 1 (Day 1) to Study Exit (Day 90)]
Arm/Group Title	0.5 mg of DE-122		1.0 mg of DE-122		2.0 mg of DE-122		4.0 mg of DE-122
Arm/Group Description	Single intravitreal injection of Low Dose DE-122		Single intravitreal injection of Medium-Low Dose DE-122		Single intravitreal injection of Medium-High Dose DE-122		Single intravitreal injection of High Dose DE-122
All Cause Mortality
	0.5 mg of DE-122		1.0 mg of DE-122		2.0 mg of DE-122		4.0 mg of DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)
Serious Adverse Events
	0.5 mg of DE-122		1.0 mg of DE-122		2.0 mg of DE-122		4.0 mg of DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	0.5 mg of DE-122		1.0 mg of DE-122		2.0 mg of DE-122		4.0 mg of DE-122
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/3 (66.7%)		2/3 (66.7%)		3/3 (100%)
Eye disorders
Conjunctival haemorrhage	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	1/3 (33.3%)	1
Deposit eye	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Foreign body sensation in eyes	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Hyphaema	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Lacrimation increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2
Photophobia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Retinal haemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Vision blurred	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Neck pain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Spinal pain	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Vascular disorders
Hypertension	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.