A Pilot Study to Evaluate the Role of High-dose Ranibizumab (2.0mg) in the Management of AMD in Patients With Persistent/Recurrent Macular Fluid Less Than 30 Days Following Treatment With Intravitreal Anti-VEGF Therapy (the LAST Study)

• Sponsor: Vitreous -Retina- Macula Consultants of New York (Other)
• Overall Status: Completed
• CT.gov ID: NCT01115556
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a single-masked study to compare intravitreally administered 0.5 mg ranibizumab to 2.0 mg ranibizumab in subjects who manifest persistent or recurrent macular fluid less than 30 days following treatment with intravitreal anti-VEGF therapy. Patients will be masked to their treatment assignment.

The study duration is anticipated to be 12 months and will enroll 30 subjects . Patients will be randomized 2:1 to either 2.0 mg ranibizumab or 0.5mg ranibizumab.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration	Drug: Ranibizumab; Drug: Ranibizumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: This is a Single-masked Study to Compare Intravitreally Administered 0.5 mg Ranibizumab to 2.0 mg Ranibizumab in Subjects Who Manifest Persistent or Recurrent Macular Fluid Less Than 30 Days Following Treatment With Intravitreal Anti-VEGF Therapy.
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lucentis 2.0 mg Lucentis 2.0 mg	Drug: Ranibizumab; 2.0 mg
Active Comparator: LUCENTIS 0.5 mg	Drug: Ranibizumab; 0.5 mg

Outcome Measures

Primary Outcome Measures

1. Mean Change in Visual Acuity (VA) From Baseline at Month 6 [Baseline and 6 months]

Secondary Outcome Measures

1. Mean Change in Visual Acuity (VA) From Baseline at Month 12 [one year]

   Mean change in Visual Acuity (VA) from Baseline at Month 12 Mean change in central foveal thickness (RPE to ILM) as measured by SD-OCT (Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) at Months 6 and 12 Mean change in leakage as determined by FA at Months 6 and 12 Mean number of ranibizumab injections at Months 6 and 12 Mean time to first re-treatment following the initial 3 monthly loading doses Mean duration of fluid-free interval Safety and tolerability of 2.0mg using the incidence and severity of adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Subjects will be eligible if the following criteria are met:

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

• Age > 50 years

• Subfoveal neovascularization secondary to AMD

• Best corrected visual acuity in the study eye between 20/30 to 20/400 using an ETDRS chart

• Documentation of the presence of subretinal fluid and/or cystoid macular edema on SD-OCT less than 30 days following at least six months of anti-VEGF therapy

• Presence of fibrosis, hemorrhage, or other hypofluorescent lesions should not obscure greater than 50% of the CNV lesion

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

• Pregnancy (positive pregnancy test) or lactation

• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

• Participation in another simultaneous medical investigation or trial

• Prior treatment with anti-VEGF therapy in the study eye within 30 days of BSL

• Prior treatment with triamcinolone in the study eye within 6 months of BSL.

• Prior treatment with dexamethasone in the study eye within 30 days prior to BSL

• Past treatment with PDT or thermal laser in the study eye

• Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding BSL

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye

• Active intraocular inflammation (grade trace or above) in the study eye

• Current vitreous hemorrhage in the study eye

• History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

• Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment with anti-glaucoma medication)

• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.

• History of allergy to fluorescein, not amenable to treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vitreous Retina Macula Consultants of New York	New York	New York	United States	10022

Sponsors and Collaborators

• Vitreous -Retina- Macula Consultants of New York
• Genentech, Inc.

Investigators

• Principal Investigator: K.Bailey Freund, MD, Vitreous -Retina- Macula Consultants of New York

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vitreous -Retina- Macula Consultants of New York
• ClinicalTrials.gov Identifier: NCT01115556
• Other Study ID Numbers: FVF4836S
• First Posted: May 4, 2010
• Last Update Posted: May 3, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Macular Degeneration; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Lucentis 2.0 mg	Lucentis 0.5 mg
Arm/Group Description	Lucentis (ranibizumab) 2.0 mg	Lucentis (ranibizumab) 0.5 mg
Period Title: Overall Study
STARTED	7	2
COMPLETED	7	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Lucentis 2.0 mg	Lucentis 0.5 mg	Total
Arm/Group Description	Lucentis (ranibizumab) 2.0 mg	Lucentis (ranibizumab) 0.5 mg	Total of all reporting groups
Overall Participants	7	2	9
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	80.1 (5.4)	88.0 (0.0)	82.0 (5.8)
Sex: Female, Male (Count of Participants)
Female	5 71.4%	1 50%	6 66.7%
Male	2 28.6%	1 50%	3 33.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Visual Acuity (VA) From Baseline at Month 6
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lucentis 2.0 mg	Lucentis 0.5 mg
Arm/Group Description	Lucentis (ranibizumab) 2.0 mg	Lucentis (ranibizumab) 0.5 mg
Measure Participants	7	2
Mean (Standard Deviation) [ETDRS Letters]	6.1 (3.7)	2.0 (0.0)

2. Secondary Outcome

Title	Mean Change in Visual Acuity (VA) From Baseline at Month 12
Description	Mean change in Visual Acuity (VA) from Baseline at Month 12 Mean change in central foveal thickness (RPE to ILM) as measured by SD-OCT (Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) at Months 6 and 12 Mean change in leakage as determined by FA at Months 6 and 12 Mean number of ranibizumab injections at Months 6 and 12 Mean time to first re-treatment following the initial 3 monthly loading doses Mean duration of fluid-free interval Safety and tolerability of 2.0mg using the incidence and severity of adverse events
Time Frame	one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lucentis 2.0 mg	LUCENTIS 0.5 mg
Arm/Group Description	Lucentis 2.0 mg Ranibizumab: 2.0 mg	Ranibizumab: 0.5 mg
Measure Participants	7	2
Mean (Standard Deviation) [ETDRS Letters]	4.1 (4.5)	3.0 (0.0)

Adverse Events

Time Frame	1 year
Arm/Group Title	Lucentis 2.0 mg		Lucentis 0.5 mg
Arm/Group Description	Lucentis (ranibizumab) 2.0 mg		Lucentis (ranibizumab) 0.5 mg
All Cause Mortality
	Lucentis 2.0 mg		Lucentis 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lucentis 2.0 mg		Lucentis 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Lucentis 2.0 mg		Lucentis 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

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.