A Safety and Efficacy Study of E10030 (Anti-PDGF Pegylated Aptamer) Plus Lucentis for Neovascular Age-Related Macular Degeneration

• Sponsor: Ophthotech Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01089517
• Collaborator: (none)
• Enrollment: 449
• Location: 1
• Arms: 3
• Duration (Months): 27
• Patients Per Site Per Month: 16.6

Study Details

Study Description

Brief Summary

The objectives of this study are to evaluate the safety and efficacy of E10030 intravitreous injection when administered in combination with Lucentis® against a control of Lucentis® alone in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: E10030 plus Lucentis; Drug: Lucentis	Phase 2

Detailed Description

Subjects will be randomized in a 1:1:1 ratio to the following dose groups:

• E10030 0.3 mg/eye + Lucentis® 0. 5 mg/eye

• E10030 1.5 mg/eye + Lucentis® 0. 5 mg/eye

• E10030 sham + Lucentis® 0. 5 mg/eye

Subjects will be treated with active E10030 or sham E10030 in combination with Lucentis® at Day 0, Week 4, Week 8, Week 12, Week 16 and Week 20.

Primary Efficacy Endpoint:

The primary efficacy endpoint is mean change in visual acuity from baseline at the Week 24 visit

Safety Endpoints:

Safety endpoints include adverse events, vital signs, ophthalmic variables [visual acuity, intraocular pressure (IOP), ophthalmic examination, color fundus photography, fluorescein angiograms (FA), optical coherence tomography (OCT)], and laboratory variables.

Approximately 444 subjects will be randomized into one of the three treatment cohorts (approximately 148 patients per dose group).

Study Design

• Study Type: Interventional
• Actual Enrollment: 449 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Masked, Controlled Trial to Establish the Safety and Efficacy of Intravitreous Injections of E10030 (Anti-PDGF Pegylated Aptamer) Given in Combination With Lucentis in Subjects With Neovascular Age-Related Macular Degeneration
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lucentis	Drug: Lucentis; 10 mg/mL intravitreal injection monthly
Experimental: E10030 low dose plus Lucentis	Drug: E10030 plus Lucentis; once a month intravitreal injection
Experimental: E10030 high dose plus Lucentis	Drug: E10030 plus Lucentis; once a month intravitreal injection

Outcome Measures

Primary Outcome Measures

1. Mean Change in Visual Acuity From Baseline at the Week 24 Visit [24 Weeks]

   The primary efficacy endpoint is the mean change in visual acuity from baseline at the Week 24 visit

Secondary Outcome Measures

1. The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit [24 weeks]

   The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit

2. Proportion of Patients With at Least 1 Adverse Event [24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subfoveal choroidal neovascularization (CNV) due to AMD

Exclusion Criteria:

Any of the following underlying diseases including:

• Diabetes mellitus

• History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 19.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrhythmias requiring ongoing treatment.

• Clinically significant impaired renal or hepatic function.

• Stroke (within 12 months of trial entry).

• Any major surgical procedure within one month of trial entry.

• Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), to the components of the ranibizumab (Lucentis) formulation, or to the components of the E10030 formulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palmetto Retinal Center	West Columbia	South Carolina	United States	29169

Sponsors and Collaborators

• Ophthotech Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ophthotech Corporation
• ClinicalTrials.gov Identifier: NCT01089517
• Other Study ID Numbers: OPH1001
• First Posted: Mar 18, 2010
• Last Update Posted: May 12, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab

Study Results

Participant Flow

Recruitment Details	This study enrolled 449 patients at approximately 69 centers in North America, South America, Europe and Israel.

Arm/Group Title	Lucentis	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Arm/Group Description	Sham/Lucentis 0.5 mg	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Period Title: Overall Study
STARTED	148	149	152
COMPLETED	144	144	147
NOT COMPLETED	4	5	5

Baseline Characteristics

Arm/Group Title	Lucentis	E10030 Low Dose Plus Lucentis	E10030 High Dose Plus Lucentis	Total
Arm/Group Description	Sham/Lucentis 0.5 mg	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg	Total of all reporting groups
Overall Participants	148	149	152	449
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 5.4%	10 6.7%	11 7.2%	29 6.5%
>=65 years	140 94.6%	139 93.3%	141 92.8%	420 93.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	78.0 (7.98)	77.6 (8.19)	77.8 (8.36)	77.8 (8.16)
Sex: Female, Male (Count of Participants)
Female	93 62.8%	90 60.4%	92 60.5%	275 61.2%
Male	55 37.2%	59 39.6%	60 39.5%	174 38.8%
Region of Enrollment (participants) [Number]
United States	47 31.8%	51 34.2%	53 34.9%	151 33.6%
Europe	87 58.8%	85 57%	82 53.9%	254 56.6%
Israel	10 6.8%	10 6.7%	14 9.2%	34 7.6%
South America	4 2.7%	3 2%	3 2%	10 2.2%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Visual Acuity From Baseline at the Week 24 Visit
Description	The primary efficacy endpoint is the mean change in visual acuity from baseline at the Week 24 visit
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (last observation carried forward)

Arm/Group Title	Lucentis	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Arm/Group Description	Sham/Lucentis 0.5 mg	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Measure Participants	147	147	151
Mean (Standard Error) [ETDRS Letters]	6.5 (1.09)	8.8 (1.09)	10.6 (1.07)

2. Secondary Outcome

Title	The Proportion of Subjects Gaining 15 or More ETDRS Letters From Baseline at the Week 24 Visit
Description	The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (last observation carried forward)

Arm/Group Title	Lucentis	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Arm/Group Description	Sham/Lucentis 0.5 mg	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Measure Participants	147	147	151
Number [% subjects (i.e gaining >/=15 letters)]	34.0	33.3	39.1

3. Secondary Outcome

Title	Proportion of Patients With at Least 1 Adverse Event
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Population

Arm/Group Title	Lucentis	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Arm/Group Description	Sham/Lucentis 0.5 mg	E10030 0.3 mg/Lucentis 0.5 mg	E10030 1.5 mg/Lucentis 0.5 mg
Measure Participants	148	149	152
Number [% of patients with adverse events]	65.5	67.1	65.1

Adverse Events

Arm/Group Title	Lucentis		E10030 Low Dose Plus Lucentis		E10030 High Dose Plus Lucentis
Arm/Group Description	Sham/Lucentis 0.5 mg		E10030 0.3 mg/Lucentis 0.5 mg		E10030 1.5 mg/Lucentis 0.5 mg
All Cause Mortality
	Lucentis		E10030 Low Dose Plus Lucentis		E10030 High Dose Plus Lucentis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lucentis		E10030 Low Dose Plus Lucentis		E10030 High Dose Plus Lucentis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/148 (8.1%)		14/149 (9.4%)		10/152 (6.6%)
Cardiac disorders
Aortic Valve Stenosis	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Atrial Fibrillation	1/148 (0.7%)		1/149 (0.7%)		0/152 (0%)
Atrial Flutter	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Cardiac Failure	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Cardiac Failure Congestive	1/148 (0.7%)		0/149 (0%)		1/152 (0.7%)
Arrhythmia	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Cardiac disorder	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Eye disorders
Corneal Erosion	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Uveitis	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Visual Acuity Reduced	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Gastrointestinal disorders
Abdominal Pain	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Constipation	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Duodenal Ulcer	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Ileus	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Inguinal Hernia, Obstructive	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Rectal Hemmorrhage	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Colitis ulcerative	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Hepatobiliary disorders
Cholelithiasis	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Infections and infestations
Osteomyelitis	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Sepsis	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Urinary Tract infection	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Bronchitis	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/148 (0%)		0/149 (0%)		2/152 (1.3%)
Spondylitis	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung squamous cell carcinoma, unspecified	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Metastatic Neoplasm	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Neoplasm skin	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Rectal Cancer	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Benign salivary gland neoplasm	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Brain Cancer Metastatic	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Breast Cancer	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Nervous system disorders
Cerebral Infarction	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Cerebrovascular Accident	2/148 (1.4%)		0/149 (0%)		0/152 (0%)
Loss of Consciousness	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Vascular Encephalopathy	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Psychiatric disorders
Mental status change	1/148 (0.7%)		0/149 (0%)		0/152 (0%)
Renal and urinary disorders
Renal colic	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	0/148 (0%)		2/149 (1.3%)		2/152 (1.3%)
Asthma	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Haemoptysis	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Vascular disorders
Arterial Disorder	0/148 (0%)		0/149 (0%)		1/152 (0.7%)
Haematoma	0/148 (0%)		1/149 (0.7%)		0/152 (0%)
Other (Not Including Serious) Adverse Events
	Lucentis		E10030 Low Dose Plus Lucentis		E10030 High Dose Plus Lucentis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/148 (42.6%)		63/149 (42.3%)		69/152 (45.4%)
Eye disorders
Conjunctival hemorrhage	37/148 (25%)		34/149 (22.8%)		51/152 (33.6%)
Punctate Keratitis	10/148 (6.8%)		19/149 (12.8%)		15/152 (9.9%)
Eye Pain	8/148 (5.4%)		10/149 (6.7%)		13/152 (8.6%)
Conjunctival hyperemia	13/148 (8.8%)		9/149 (6%)		13/152 (8.6%)
Subretinal fibrosis	8/148 (5.4%)		6/149 (4%)		5/152 (3.3%)
Investigations
Intraocular pressure increased	4/148 (2.7%)		8/149 (5.4%)		9/152 (5.9%)
Vascular disorders
Hypertension	8/148 (5.4%)		7/149 (4.7%)		5/152 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

No individual site or investigator may publish or present any results from the trial until a joint, multi center publication of the trial results is made by Sponsor in conjunction with various participating investigators and appropriate sites contributing data and comments. Subsequently, individual investigators may request to publish or present results from the trial; however, approval will be at the sole discretion of the Sponsor.