COBALT: Safety & Efficacy Study Evaluating the Combination of Bevasiranib & Lucentis Therapy in Wet AMD

• Sponsor: OPKO Health, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00499590
• Collaborator: (none)
• Enrollment: 338
• Locations: 60
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and effectiveness of bevasiranib given either every 8 weeks or every 12 weeks after an initial pre-treatment with 3 injections of Lucentis® (ranibizumab injection) compared to Lucentis® given every 4 weeks to people with wet AMD. Patients will be assigned at random (like tossing a coin) to receive one of three treatments options for 104 weeks.

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Drug: bevasiranib; Drug: ranibizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 338 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-masked, Parallel-assignment Study of Intravitreal Bevasiranib Sodium, Administered Every 8 or 12 Weeks as Maintenance Therapy Following Three Injections of Lucentis® Compared With Lucentis® Monotherapy Every 4 Weeks in Patients With Exudative Age-Related Macular Degeneration (AMD).
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A Lucentis® (0.5mg) every 4 weeks.	Drug: ranibizumab; Lucentis® (0.5 mg)administered intravitreally every 4 weeks.; Other Names: Lucentis®
Experimental: B Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6.	Drug: bevasiranib; Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks
Experimental: C Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6.	Drug: bevasiranib; Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks

Outcome Measures

Primary Outcome Measures

1. Visual Acuity [week 60]

   avoidance of 3 or more lines of vision loss

Secondary Outcome Measures

1. Need for Rescue Therapy, Time to Rescue Therapy, and Number of Patients With a 3 or More Line Gain in Vision [Week 60]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients must be age 50 years or older

2. Patients must have predominantly classic, minimally classic or occult with no classic lesions secondary to Age Related Macular Degeneration.

3. The study eye must have ETDRS best corrected visual acuity of 69 to 24 letters (20/40 to 20/320 Snellen equivalent).

4. Patients must be willing and able to return for scheduled monthly follow-up visits for two-years.

Exclusion Criteria:

1. Prior pharmacologic treatment for AMD in the study (patients can not have previously received Avastin®/Lucentis®, Macugen®, or any other anti-VEGF agents, steroid treatments, PDT, radiation treatment, or any experimental therapies for AMD in the study eye)

2. Any intraocular surgery of the study eye within 12 weeks of screening

3. Previous posterior vitrectomy of the study eye

4. Advanced glaucoma or intraocular pressure above 22 mm Hg in the study eye despite treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona (site 209)	Phoenix	Arizona	United States	85014
2	Associated Retina Consultants (site 286)	Phoenix	Arizona	United States	85020
3	Retina Centers PC (site 215)	Tucson	Arizona	United States	85704
4	Eye Medical Center (site 287)	Fresno	California	United States	93720
5	Northern California Retina Vitreous Associates (site 320)	Mountain View	California	United States	94040
6	Retina Institute of California (site 207)	Pasadena	California	United States	91105
7	Retina Consultants San Diego (site 232)	Poway	California	United States	93064
8	Retinal Consultants Medical Group (site 289)	Sacramento	California	United States	95819
9	Orange County Retina Medical Group (site 252)	Santa Ana	California	United States	92705
10	Miramar Eye Specialists Medical Group (site 245)	Ventura	California	United States	93003
11	The Eye Care Group, PC (site 315)	Waterbury	Connecticut	United States	06708
12	Florida Eye Clinic (site 257)	Altamonte Springs	Florida	United States	32701
13	Florida Eye Microsurgical Institute, Inc. (site 217)	Boynton Beach	Florida	United States	33426
14	Retina Health Center (site 247)	Fort Myers	Florida	United States	33901
15	National Ophthalmic Research Institute at Retina Consultants of SW Florida (site 270)	Fort Myers	Florida	United States	33912
16	Magruder Eye Institute (site 264)	Orlando	Florida	United States	32803
17	Southern Vitreoretinal Associates, PL (site 309)	Tallahassee	Florida	United States	32308
18	University of South Florida Eye Institute (site 311)	Tampa	Florida	United States	33612
19	Center for Retina and Macular Disease (site 293)	Winter Haven	Florida	United States	33880
20	Southeast Retina Center (site 268)	Augusta	Georgia	United States	30909
21	Midwest Eye Institute (site 253)	Indianapolis	Indiana	United States	46280
22	Retina Associates, PA (site 295)	Shawnee Mission	Kansas	United States	66204
23	Vitreo-Retinal Consultants & Surgeons, P.A. (site 274)	Wichita	Kansas	United States	67214
24	Eye Centers of Louisville (site 251)	Louisville	Kentucky	United States	40207
25	Retina Specialists (site 231)	Towson	Maryland	United States	21204
26	Retina Associates St. Louis (site 300)	Florissant	Missouri	United States	63031
27	Eye Foundation of Kansas City Truman Medical Center (site 272)	Kansas City	Missouri	United States	64108
28	Retinal Consultants of Nevada (site 273)	Las Vegas	Nevada	United States	89144
29	Eyesight Ophthalmic Services, PA (site 290)	Portsmouth	New Hampshire	United States	03801
30	Delaware Valley Retina Associates (site 261)	Lawrenceville	New Jersey	United States	08648
31	Retina-Vitreous Consultants (site 216)	Livingston	New Jersey	United States	07039
32	Retina Associates of New Jersey (site 298)	Teaneck	New Jersey	United States	07666
33	Capital Region Retina (site 316)	Albany	New York	United States	12206
34	New York Eye & Ear Infirmary (site 272)	New York	New York	United States	10003
35	Vitreous-Retina-Macula Consultants of New York (site 239)	New York	New York	United States	10022
36	Carolina Eye Associates (site 308)	Southern Pines	North Carolina	United States	28387
37	Retina Associates of Cleveland (site 228)	Beachwood	Ohio	United States	44122
38	Cincinnati Eye Institute (site 285)	Cincinnati	Ohio	United States	45242
39	Retina Associates of Cleveland, Inc. (site 219)	Lakewood	Ohio	United States	44107
40	Retina-Vitreous Associates (site 266)	Toledo	Ohio	United States	43608
41	Retina and Vitreous Center of Southern Oregon (site 271)	Ashland	Oregon	United States	97520
42	Ophthalmology Associates of PA (site 297)	Bala Cynwyd	Pennsylvania	United States	19004
43	Palmetto Retina Center (site 275)	West Columbia	South Carolina	United States	29169
44	Black Hills Regional Eye Institute (site 202)	Rapid City	South Dakota	United States	57701
45	Southeastern Retina Associates, PC (Site 250)	Knoxville	Tennessee	United States	37909
46	Retina Research Institute of Texas, L.L.C. (site 269)	Abilene	Texas	United States	79606
47	Austin Retina Associates (site 304)	Austin	Texas	United States	78705
48	Retina Research Center (site 204)	Austin	Texas	United States	78705
49	University of Texas Medical Branch- Galveston (site 301	Galveston	Texas	United States	77555
50	Houston Eye Associates (site 321)	Houston	Texas	United States	77025
51	Valley Retina Institue, PA (site 258)	McAllen	Texas	United States	78503
52	Eye Care Associates of East Texas (site 282)	Tyler	Texas	United States	75701
53	Rocky Mountain Retina Consultants (site 256)	Salt Lake City	Utah	United States	84107
54	University of Utah, John A. Moran Eye Center (site 205)	Salt Lake City	Utah	United States	84132
55	University of Virginia- Ophthalmology Dept. (site 254)	Charlottesville	Virginia	United States	22908
56	Calgary Retina Consultants (site 318)	Calgary	Alberta	Canada	T3E 7M8
57	Ivey Eye Institute (site 314)	London	Ontario	Canada	N6A 4G5
58	Canadian Centre for Advanced Eye Therapeutics (site 291)	Mississauga	Ontario	Canada	L4W 1W9
59	Sunnybrook Health Sciences Centre (site 305)	Toronto	Ontario	Canada	M4N 3M5
60	Eye Centre Pasqua Hospital (site 299)	Regina	Saskatchewan	Canada	S4T 1A5

Sponsors and Collaborators

• OPKO Health, Inc.

Investigators

• Study Director: Denis O'Shaughnessy, Ph.D., Senior VP of Clincial Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OPKO Health, Inc.
• ClinicalTrials.gov Identifier: NCT00499590
• Other Study ID Numbers: ACU301
• First Posted: Jul 11, 2007
• Last Update Posted: Oct 6, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by OPKO Health, Inc.: AMD; Macular Degeneration; bevasiranib; COBALT study; age related macular degeneration; wet AMD; wet age related macular degeneration
• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Lucentis®	Bevasiranib 8 Weeks	Bevasiranib 12 Weeks
Arm/Group Description	Lucentis® (0.5mg) every 4 weeks. ranibizumab: Lucentis® (0.5 mg)administered intravitreally every 4 weeks.	Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks	Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks
Period Title: Overall Study
STARTED	113	112	113
COMPLETED	0	0	0
NOT COMPLETED	113	112	113

Baseline Characteristics

Arm/Group Title	Lucentis	Bevasiranib 8 Weeks	Bevasiranib 12 Weeks	Total
Arm/Group Description	Lucentis® (0.5mg) every 4 weeks. ranibizumab: Lucentis® (0.5 mg)administered intravitreally every 4 weeks.	Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks	Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks	Total of all reporting groups
Overall Participants	113	112	113	338
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	77.6	77.2	78.3	77.7
Sex: Female, Male (Count of Participants)
Female	80 70.8%	72 64.3%	59 52.2%	211 62.4%
Male	33 29.2%	40 35.7%	54 47.8%	127 37.6%
Region of Enrollment (participants) [Number]
United States	61 54%	59 52.7%	64 56.6%	184 54.4%
Austria	4 3.5%	5 4.5%	4 3.5%	13 3.8%
Canada	8 7.1%	10 8.9%	5 4.4%	23 6.8%
France	22 19.5%	24 21.4%	20 17.7%	66 19.5%
Israel	9 8%	7 6.3%	6 5.3%	22 6.5%
Italy	5 4.4%	2 1.8%	2 1.8%	9 2.7%
Portugal	3 2.7%	3 2.7%	5 4.4%	11 3.3%
Spain	1 0.9%	2 1.8%	7 6.2%	10 3%

Outcome Measures

1. Primary Outcome

Title	Visual Acuity
Description	avoidance of 3 or more lines of vision loss
Time Frame	week 60

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to early termination of the study.

Arm/Group Title	Lucentis®	Bevasiranib 8 Weeks	Bevasiranib 12 Weeks
Arm/Group Description	Lucentis® (0.5mg) every 4 weeks. ranibizumab: Lucentis® (0.5 mg)administered intravitreally every 4 weeks.	Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks	Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks
Measure Participants	0	0	0

2. Secondary Outcome

Title	Need for Rescue Therapy, Time to Rescue Therapy, and Number of Patients With a 3 or More Line Gain in Vision
Time Frame	Week 60

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to early termination of the study.

Arm/Group Title	Lucentis	Bevasiranib 8 Weeks	Bevasiranib 12 Weeks
Arm/Group Description	Lucentis® (0.5mg) every 4 weeks. ranibizumab: Lucentis® (0.5 mg)administered intravitreally every 4 weeks.	Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks	Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks
Measure Participants	0	0	0

Adverse Events

Time Frame	Study was terminated early. Adverse events collected from first enrolled until study terminated, approximately 20 months.
Adverse Event Reporting Description	Safety population included randomized participants who received at least one treatment. Therefore the number of participants analyzed in the Lucentis and Bevasiranib 12 Weeks is one participant fewer than the number of participants randomized.
Arm/Group Title	Lucentis		Bevasiranib 8 Weeks		Bevasiranib 12 Weeks
Arm/Group Description	Lucentis® (0.5mg) every 4 weeks. ranibizumab: Lucentis® (0.5 mg)administered intravitreally every 4 weeks.		Bevasiranib (2.5mg) every 8 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks		Bevasiranib (2.5mg) every 12 weeks beginning at week 12, after pre-treatment with 3 injections of Lucentis® and initial priming doses of bevasiranib at weeks 2 & 6. bevasiranib: Bevasiranib (2.5mg) administered intravitreally every 8 or 12 weeks
All Cause Mortality
	Lucentis		Bevasiranib 8 Weeks		Bevasiranib 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lucentis		Bevasiranib 8 Weeks		Bevasiranib 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/112 (23.2%)		28/112 (25%)		33/112 (29.5%)
Blood and lymphatic system disorders
Anaemia	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Cardiac disorders
Atrial fibrillation	1/112 (0.9%)		1/112 (0.9%)		0/112 (0%)
Myocardial infarction	1/112 (0.9%)		1/112 (0.9%)		0/112 (0%)
Acute myocardial infarction	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Angina pectoris	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Coronary artery disease	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Ear and labyrinth disorders
Vertigo	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Eye disorders
Visual acuity decreased	5/112 (4.5%)		7/112 (6.3%)		10/112 (8.9%)
Endophthalmitis	0/112 (0%)		4/112 (3.6%)		1/112 (0.9%)
Uveitis	0/112 (0%)		1/112 (0.9%)		2/112 (1.8%)
Vitritis	0/112 (0%)		3/112 (2.7%)		0/112 (0%)
Vitreous haemorrhage	0/112 (0%)		0/112 (0%)		2/112 (1.8%)
Cataract	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Corneal oedema	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Hyphaema	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Iridocyclitis	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Macular degeneration	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Punctate keratitis	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Gastroduodenitis	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Gastrointestinal haemorrhage	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Intestinal obstruction	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Pancreatitis	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
General disorders
Asthenia	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Immune system disorders
Anaphylactic reaction	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Infections and infestations
Pneumonia	1/112 (0.9%)		0/112 (0%)		2/112 (1.8%)
Bronchitis	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Gastroenteritis viral	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Keratitis herpetic	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Injury, poisoning and procedural complications
Fall	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Hip fracture	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Injury	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Upper limb fracture	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Investigations
Heart rate irregular	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Metabolism and nutrition disorders
Dehydration	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Hyponatraemia	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/112 (0.9%)		1/112 (0.9%)		0/112 (0%)
Arthritis	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Intervertebral disc protusion	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Musculoskeletal chest pain	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Rhabdomyolysis	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	0/112 (0%)		2/112 (1.8%)		0/112 (0%)
Colon cancer recurrent	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Lung neoplasm malignant	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Metastases to spine	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Nervous system disorders
Cerebrovascular accident	2/112 (1.8%)		0/112 (0%)		2/112 (1.8%)
Syncope	0/112 (0%)		0/112 (0%)		2/112 (1.8%)
Transient ischemia attack	0/112 (0%)		0/112 (0%)		2/112 (1.8%)
Carotid artery stenosis	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Dementia	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Headache	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Renal and urinary disorders
Renal failure chronic	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/112 (0%)		2/112 (1.8%)		0/112 (0%)
Acute respiratory failure	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Chronic obstructive pulmonary disease	0/112 (0%)		0/112 (0%)		1/112 (0.9%)
Pleural effusion	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Respiratory failure	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Vascular disorders
Deep vein thrombosis	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Hypotension	1/112 (0.9%)		0/112 (0%)		0/112 (0%)
Thrombosis	0/112 (0%)		1/112 (0.9%)		0/112 (0%)
Other (Not Including Serious) Adverse Events
	Lucentis		Bevasiranib 8 Weeks		Bevasiranib 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/112 (63.4%)		85/112 (75.9%)		96/112 (85.7%)
Eye disorders
Retinal haemorrhage	11/112 (9.8%)		16/112 (14.3%)		22/112 (19.6%)
Visual acuity reduced	4/112 (3.6%)		8/112 (7.1%)		12/112 (10.7%)
Conjunctival haemorrhage	10/112 (8.9%)		9/112 (8%)		13/112 (11.6%)
Vitreous detachment	8/112 (7.1%)		11/112 (9.8%)		10/112 (8.9%)
Vitreous floaters	9/112 (8%)		10/112 (8.9%)		8/112 (7.1%)
Eye pain	6/112 (5.4%)		7/112 (6.3%)		12/112 (10.7%)
Macular degeneration	5/112 (4.5%)		7/112 (6.3%)		9/112 (8%)
Cataract	8/112 (7.1%)		4/112 (3.6%)		6/112 (5.4%)
Infections and infestations
Nasopharyngitis	7/112 (6.3%)		6/112 (5.4%)		5/112 (4.5%)
Investigations
Intraocular pressure increased	3/112 (2.7%)		7/112 (6.3%)		10/112 (8.9%)

Limitations/Caveats

Study was terminated early.

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.