Lucentis Utilizing Visudyne (LUV Trial) Combination Therapy in the Treatment of Age-Related Macular Degeneration

• Sponsor: David M. Brown, M.D. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00423189
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 7
• Location: 1
• Arms: 3
• Duration (Months): 24
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The PDT/Lucentis trial will be a Phase IV comparative trial comparing the use of combination therapy with ITV ranibizumab and verteporfin PDT to ITV ranibizumab alone in patients with exudative AMD.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: Ranibizumab (Lucentis); Drug: 0.5mg ranibizumab	Phase 4

Detailed Description

The PDT/Lucentis trial will be a Phase IV comparative trial comparing the use of combination therapy with ITV ranibizumab and verteporfin PDT to ITV ranibizumab alone in patients with exudative AMD. Patients will be randomized to one of three groups. All patients will receive three consecutive monthly treatments with ITV ranibizumab. Patients randomized to group I will receive only ITV ranibizumab. Patients randomized to group II will also receive one treatment with reduced fluence (20% fluence) verteporfin PDT at day 0. Patients randomized to group III will also receive one treatment with reduced fluence (40% fluence) vPDT. All patients will also be evaluated for possible retreatment with ranibizumab according to established criteria. Thirty patients (ten per group) will be recruited from one U.S. sites in a 6-month period. Randomization will occur at the time of entry into the study. Follow-up will continue until month 12 (from day 0) in all subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lucentis Utilizing Visudyne (LUV Trial)-- Reduced Fluence Photodynamic Therapy With Visudyne Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranibizumab only drug - intravitreal ranibizumab	Drug: Ranibizumab (Lucentis); as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: PDT Photodynamic Therapy ; Drug: 0.5mg ranibizumab; as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: lucentis
Experimental: 40% fluence PDT/procedure 40% fluence photodynamic therapy-PDT therapy with 0.5mg ranibizumab	Drug: Ranibizumab (Lucentis); as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: PDT Photodynamic Therapy ; Drug: 0.5mg ranibizumab; as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: lucentis
Experimental: 20% fluence photodynamic therapy 20% fluence photodynamic therapy-PDT therapy with 0.5mg ranibizumab	Drug: Ranibizumab (Lucentis); as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: PDT Photodynamic Therapy ; Drug: 0.5mg ranibizumab; as needed, one intravitreal injection of 0.50mg ranibizumab; Other Names: lucentis

Outcome Measures

Primary Outcome Measures

1. Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months) [1 Year]

   Visual Acuity was measured by ETDRS by certified refractionists in certified lanes at 12 months. Visual Acuity was not measured by ETDRS at 6 months.

Secondary Outcome Measures

1. Number of Intravitreal Injections With Ranibizumab Needed by Patients at 12 Months [1 Year]

   Number of intravitreal injections with ranibizumab needed by patients at 12 months was not determined due to lack of efficacy.

2. OCT 3 Macular Thickness Improvement (Baseline-1month, 2months, 3months, 6months &12 Months) [1 Year]

   OCT 3 macular thickness improvement at Baseline-1month, 2months, 3months, 6months &12 months was not determined due to lack of efficacy.

3. Choroidal Perfusion as Assessed by ICG Angiography at 1, 2, 3, 6, and 12 Months [1 Year]

   Choroidal perfusion as assessed by ICG angiography at 1, 2, 3, 6, and 12 months was not determined due to lack of efficacy

4. Safety of Combination Therapy With Verteporfin PDT and ITV Ranibizumab [1 Year]

   Safety of combination therapy with verteporfin PDT and ITV ranibizumab was not determined due to lack of efficacy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

• Age > 55 years

• Subfoveal neovascular membrane confirmed by fluorescein angiography and or ICG

• Visual acuity not better than 20/32 and not worse than 20/320 by ETDRS refraction

Exclusion Criteria:

• Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)

• Intracapsular cataract extraction (posterior capsule needs to be present)

• Previous treatment with ranibizumab

• Previous treatment with pegaptanib

• Previous treatment with ITV triamcinolone

• Any previous treatment with photodynamic therapy

• Previous history of retinal detachment in study eye

• Any previous radiation treatments to head/ neck

• Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study

• Prior enrollment in any study for AMD in the study eye

• Participation in another simultaneous medical investigator or trial

• Ocular disorders in the study eye that may confound interpretation of study results, including retinal detachment or macular hole.

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

• Aphakia or absence of the posterior capsule in the study eye

• Previous violation of the posterior capsule is also excluded unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation

• History of idiopathic or autoimmune uveitis in either eye

• Significant structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)

• Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT

• Ocular inflammation (including trace or above) in the study eye

• Uncontrolled glaucoma (defined as intraocular pressure ≥30 mm Hg despite treatment with anti- medications) or previous filtration surgery in the study eye

• Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection

• Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, pre-operative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)

Systemic Conditions

• Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during the screening period

• Uncontrolled diabetes mellitus

• Renal failure requiring dialysis or renal transplant

• Premenopausal women not using adequate contraception

• Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months preceding Day 0

• History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications

• INR ≥ 3.0 (e.g. due to current treatment with warfarin). The use of aspirin is not an exclusion.

Other

• History of allergy to fluorescein, not amenable to treatment

• History of allergy to shellfish

• History of allergy to intravenous iodine

• History of allergy to indocyanine green

• Inability to obtain fundus photographs or angiograms of sufficient quality to be analyzed and graded by the central reading center

• Inability to comply with study or follow up procedures

• History of allergy to humanized antibodies or any component of the ranibizumab formulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vitreoretinal Consultants	Houston	Texas	United States	77030

Sponsors and Collaborators

• David M. Brown, M.D.
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: David M Brown, M.D., Vitreoretinal Consultants

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• GreaterHRR website

Publications

• Azab M, Boyer DS, Bressler NM, Bressler SB, Cihelkova I, Hao Y, Immonen I, Lim JI, Menchini U, Naor J, Potter MJ, Reaves A, Rosenfeld PJ, Slakter JS, Soucek P, Strong HA, Wenkstern A, Su XY, Yang YC; Visudyne in Minimally Classic Choroidal Neovascularization Study Group. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Arch Ophthalmol. 2005 Apr;123(4):448-57.
• Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44.
• Michels S, Hansmann F, Geitzenauer W, Schmidt-Erfurth U. Influence of treatment parameters on selectivity of verteporfin therapy. Invest Ophthalmol Vis Sci. 2006 Jan;47(1):371-6.
• Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31.

• Responsible Party: David M. Brown, M.D., Director of Research, Greater Houston Retina Research
• ClinicalTrials.gov Identifier: NCT00423189
• Other Study ID Numbers: LUV
• First Posted: Jan 18, 2007
• Last Update Posted: Mar 4, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by David M. Brown, M.D., Director of Research, Greater Houston Retina Research: LUV; Lucentis; Visudyne; PDT; AMD; ARMD; Age; Related; Macular; Degeneration
• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab

Study Results

Participant Flow

Recruitment Details	7 patients, over a 12 month period were followed after receiving treatment of either decreased fluence(2 different fluences) and 0.5mg ranibizumab, as compared to monotherapy of 0.5mg ranibizumab at a single site
Pre-assignment Detail	patients that were considered to have recalcitrant wet age related macular degeneration were recruited for this trial

Arm/Group Title	Ranibizumab Only	Ranibizumab and 40% Fluence PDT(Procedure)	Ranibizumab and 20% Fluence PDT(Procedure)
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy - procedure	20% fluence photodynamic therapy - procedure
Period Title: Overall Study
STARTED	2	3	2
COMPLETED	2	2	2
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Total
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy - procedure	20% fluence photodynamic therapy - procedure	Total of all reporting groups
Overall Participants	2	3	2	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (3)	78 (7)	67 (5)	72 (5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	2 100%	3 100%	2 100%	7 100%
Region of Enrollment (participants) [Number]
United States	2 100%	03 100%	2 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	Best-corrected ETDRS Visual Acuity at 6 Months and 12 Months Only Time Points (Gain or Loss of >15 Letters at 12 Months)
Description	Visual Acuity was measured by ETDRS by certified refractionists in certified lanes at 12 months. Visual Acuity was not measured by ETDRS at 6 months.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

As per subjects participated

Arm/Group Title	Ranibizumab Only	40% Fluence PDT/Ranibizumab	20% Fluence PDT/Ranibizumab
Arm/Group Description	IVT Ranibizumab only	40% Fluence PDT WITH ivt Ranibizumab	20% Fluence PDT with IVT Ranibizumab
Measure Participants	2	3	2
Number [participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Intravitreal Injections With Ranibizumab Needed by Patients at 12 Months
Description	Number of intravitreal injections with ranibizumab needed by patients at 12 months was not determined due to lack of efficacy.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

not determined due to lack of efficacy

Arm/Group Title	Ranibizumab Only	40% Fluence Photodynamic Therapy Combined With Ranibizumab	20% Fluence Photodynamic Therapy Combined With Ranibizumab
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy combined with ranibizumab- procedure	20% fluence photodynamic therapy combined with ranibizumab- procedure
Measure Participants	0	0	0

3. Secondary Outcome

Title	OCT 3 Macular Thickness Improvement (Baseline-1month, 2months, 3months, 6months &12 Months)
Description	OCT 3 macular thickness improvement at Baseline-1month, 2months, 3months, 6months &12 months was not determined due to lack of efficacy.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab Only	40% Fluence Photodynamic Therapy Combined With Ranibizumab	20% Fluence Photodynamic Therapy Combined With Ranibizumab
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy combined with ranibizumab- procedure	20% fluence photodynamic therapy combined with ranibizumab- procedure
Measure Participants	0	0	0

4. Secondary Outcome

Title	Choroidal Perfusion as Assessed by ICG Angiography at 1, 2, 3, 6, and 12 Months
Description	Choroidal perfusion as assessed by ICG angiography at 1, 2, 3, 6, and 12 months was not determined due to lack of efficacy
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab Only	40% Fluence Photodynamic Therapy Combined With Ranibizumab	20% Fluence Photodynamic Therapy Combined With Ranibizumab
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy combined with ranibizumab- procedure	20% fluence photodynamic therapy combined with ranibizumab- procedure
Measure Participants	0	0	0

5. Secondary Outcome

Title	Safety of Combination Therapy With Verteporfin PDT and ITV Ranibizumab
Description	Safety of combination therapy with verteporfin PDT and ITV ranibizumab was not determined due to lack of efficacy.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab Only	40% Fluence Photodynamic Therapy Combined With Ranibizumab	20% Fluence Photodynamic Therapy Combined With Ranibizumab
Arm/Group Description	drug - intravitreal ranibizumab	40% fluence photodynamic therapy/combined with ranibizumab - procedure	20% fluence photodynamic therapy combined with ranibizumab - procedure
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	Ranibizumab Only		40% Fluence PDT Combined With Ranibizumab		20% PDT Fluence Combined With Ranibizumab
Arm/Group Description	subject only received ranibizumab		Subjects who have received 40% fluence PDT combined with as needed dosing with ranibizumab		Subjects who received 20% with as needed ranibizumab
All Cause Mortality
	Ranibizumab Only		40% Fluence PDT Combined With Ranibizumab		20% PDT Fluence Combined With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab Only		40% Fluence PDT Combined With Ranibizumab		20% PDT Fluence Combined With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		1/3 (33.3%)		0/2 (0%)
Eye disorders
Death of unknown origin	0/2 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Ranibizumab Only		40% Fluence PDT Combined With Ranibizumab		20% PDT Fluence Combined With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		1/3 (33.3%)		1/2 (50%)
Eye disorders
1+ Nuclear Sclerosis	1/2 (50%)	2	1/3 (33.3%)	3	1/2 (50%)	2
2+ nuclear sclerosis	1/2 (50%)	2	1/3 (33.3%)	3	1/2 (50%)	2

Limitations/Caveats

The trial was discontinued due to a lack of efficacy.

More Information

Certain Agreements

All Principal Investigators ARE 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.