Reduced Fluence Photodynamic Therapy (PDT) With Visudyne in Combination With Lucentis for Age-Related Macular Degeneration

• Sponsor: Oklahoma State University Center for Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00473642
• Collaborator: Novartis (Industry)
• Enrollment: 31
• Location: 1
• Arms: 3
• Duration (Months): 35
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

In this pilot study the researchers will evaluate the safety and efficacy of 50% reduced fluence PDT combination therapy with ranibizumab. The researchers hope to gain information regarding the use of reduced fluence PDT combination therapy. The information gained from this pilot study may prompt further definitive studies comparing the safety and efficacy of both standard fluence PDT combination therapy, reduced fluence PDT combination therapy, and ranibizumab monotherapy.

The study will compare the use of combination therapy with ranibizumab and verteporfin PDT to ranibizumab alone in patients with exudative age-related macular degeneration (AMD). All patients will receive three consecutive monthly treatments with ranibizumab. Patients will be randomized 1:1:1 to 3 groups. Patients randomized to group 1 will receive only ranibizumab. Patients randomized to group 2 will also receive one treatment with reduced fluence (50% fluence) verteporfin PDT at day 0. Patients randomized to group 3 will also receive one treatment with standard fluence verteporfin PDT. All patients will also be evaluated for possible retreatment with ranibizumab and verteporfin PDT according to established criteria. Thirty patients will be recruited from one U.S. sites. Randomization will occur at the time of entry into the study. Follow-up will continue until month 12 (from day 0) in all subjects.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Maculopathy; Choroidal Neovascularization	Drug: Ranibizumab; Drug: Verteporfin; Drug: Verteporfin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Pilot Study of Reduced Fluence Photodynamic Therapy With Visudyne® (Verteporfin) in Combination With Lucentis™ (Ranibizumab) for the Treatment of Age-Related Macular Degeneration
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Standard Fluence Photodynamic Therapy combined with ranibizumab	Drug: Ranibizumab; intravitreal administered ranibizumab 0.5 mg in 0.05 mL; Other Names: Lucentis ; Drug: Verteporfin; Verteporfin with standard fluence photodynamic therapy (50 J/cm2); Other Names: Visudyne
Experimental: 2 Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab	Drug: Ranibizumab; intravitreal administered ranibizumab 0.5 mg in 0.05 mL; Other Names: Lucentis ; Drug: Verteporfin; Verteporfin with 50% fluence photodynamic therapy (25 J/cm2); Other Names: Visudyne
Active Comparator: 3 Ranibizumab monotherapy	Drug: Ranibizumab; intravitreal administered ranibizumab 0.5 mg in 0.05 mL; Other Names: Lucentis

Outcome Measures

Primary Outcome Measures

1. Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months [12 months]

   Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.

2. Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol [12 months]

   Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.

Secondary Outcome Measures

1. Time to First Retreatment After Loading Doses [12 months]

2. Average Number of PDT Retreatments Over 12 Months [12 months]

3. Central Macular Thickness Reduction on OCT [12 months]

4. Average Number of Ranibizumab Retreatments Over 12 Months [12 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male or Female Patients > 50 years of age.

2. Patients with primary subfoveal CNV secondary to AMD documented on IVFA and/or OCT.

3. Patient with BCVA of 20/40 to 20/320 in the study eye using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. See definition of ETDRS charts.

4. If both eyes are eligible, only one eye will be evaluated in the study. The eye with lesser visual acuity will be selected as the study eye.

5. Patients must be able and willing to provide written informed consent.

Exclusion Criteria:

1. Patients receiving prior treatment in the study eye with verteporfin, any focal laser photocoagulation, vitrectomy, or intravitreous injection of antiangiogenic medications, including triamcinolone, pegaptanib, bevacizumab, or ranibizumab.

2. Neovascular membrane from any other retinal disease such as myopic degeneration, histoplasmosis, retinal angiomatous proliferation, or other ocular inflammatory disease.

3. Choroidal neovascular membrane greater than 9 disc diameters in size.

4. Previous posterior vitrectomy in the study eye.

5. Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period.

6. Pregnant women or premenopausal women not using adequate contraception.

7. History of allergy to fluorescein, Visudyne, Lucentis.

8. Inability to comply with study or follow up procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eagle Mountain Vision	Tulsa	Oklahoma	United States	74132

Sponsors and Collaborators

• Oklahoma State University Center for Health Sciences
• Novartis

Investigators

• Principal Investigator: Scott J Westhouse, DO, Oklahoma State University Medical Center
• Principal Investigator: Raymond Townsend, MD, Oklahoma State University Medical Center
• Principal Investigator: John Saurino, DO, Oklahoma State University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oklahoma State University Center for Health Sciences
• ClinicalTrials.gov Identifier: NCT00473642
• Other Study ID Numbers: 2007002
• First Posted: May 15, 2007
• Last Update Posted: Nov 6, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Oklahoma State University Center for Health Sciences: Ranibizumab; Lucentis; Verteporfin; Visudyne; Photodynamic therapy
• Additional relevant MeSH terms: Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Ranibizumab; Verteporfin

Study Results

Participant Flow

Arm/Group Title	Standard Fluence PDT	50% Fluence PDT	Ranibizumab
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab	Ranibizumab monotherapy
Period Title: Overall Study
STARTED	10	11	10
COMPLETED	8	10	8
NOT COMPLETED	2	1	2

Baseline Characteristics

Arm/Group Title	Standard Fluence PDT	50% Fluence PDT	Ranibizumab	Total
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab	Ranibizumab monotherapy	Total of all reporting groups
Overall Participants	10	11	10	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 10%	2 18.2%	1 10%	4 12.9%
>=65 years	9 90%	9 81.8%	9 90%	27 87.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.9 (3.1)	73.4 (2.1)	76.3 (2.8)	74 (2.7)
Sex: Female, Male (Count of Participants)
Female	8 80%	7 63.6%	8 80%	23 74.2%
Male	2 20%	4 36.4%	2 20%	8 25.8%
Region of Enrollment (participants) [Number]
United States	10 100%	11 100%	10 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months
Description	Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	Reduced Fluence PDT	Ranibizumab Monotherapy
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with standard fluence photodynamic therapy (50 J/cm2)	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)	Ranibizumab monotherapy Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL
Measure Participants	10	11	10
Mean (95% Confidence Interval) [Letters]	5.9	7.6	16.4

2. Primary Outcome

Title	Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol
Description	Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	50% Fluence PDT	Ranibizumab
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab	Ranibizumab monotherapy
Measure Participants	10	11	10
Mean (Standard Deviation) [letters]	5.9 (6.3)	7.6 (4)	16.4 (4)

3. Secondary Outcome

Title	Time to First Retreatment After Loading Doses
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	Reduced Fluence PDT	Ranibizumab Monotherapy
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with standard fluence photodynamic therapy (50 J/cm2)	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)	Ranibizumab monotherapy Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL
Measure Participants	10	11	10
Mean (Standard Deviation) [Month]	2.86 (0.38)	2.90 (0.71)	2.86 (0.63)

4. Secondary Outcome

Title	Average Number of PDT Retreatments Over 12 Months
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	Reduced Fluence PDT
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with standard fluence photodynamic therapy (50 J/cm2)	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)
Measure Participants	10	11
Mean (Standard Deviation) [Number of Treatments]	0.67 (0.24)	0.55 (0.22)

5. Secondary Outcome

Title	Central Macular Thickness Reduction on OCT
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	Reduced Fluence PDT	Ranibizumab Monotherapy
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with standard fluence photodynamic therapy (50 J/cm2)	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)	Ranibizumab monotherapy Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL
Measure Participants	10	11	10
Mean (Standard Deviation) [micron (um)]	42.9 (20.1)	76.1 (37.8)	34.9 (10.9)

6. Secondary Outcome

Title	Average Number of Ranibizumab Retreatments Over 12 Months
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Fluence PDT	Reduced Fluence PDT	Ranibizumab Monotherapy
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with standard fluence photodynamic therapy (50 J/cm2)	Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL Verteporfin: Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)	Ranibizumab monotherapy Ranibizumab: intravitreal administered ranibizumab 0.5 mg in 0.05 mL
Measure Participants	10	11	10
Mean (Standard Deviation) [Number of Treatments]	2.67 (0.53)	2.91 (0.62)	4.14 (0.72)

Adverse Events

Arm/Group Title	Standard Fluence PDT		50% Fluence PDT		Ranibizumab
Arm/Group Description	Standard Fluence Photodynamic Therapy combined with ranibizumab		Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab		Ranibizumab monotherapy
All Cause Mortality
	Standard Fluence PDT		50% Fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Fluence PDT		50% Fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		2/10 (20%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
cardiopulmonary arrest	0/10 (0%)	0	0/11 (0%)	0	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Standard Fluence PDT		50% Fluence PDT		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/10 (0%)

Limitations/Caveats

This study was limited by a small number of subjects. Additionally, several subjects did not meet the 12 month study endpoint. These subjects were included in the final analysis if their last visit was within 2 months of the final endpoint.

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.