HiPED - High Dose Lucentis for Persistent Pigment Epithelial Detachments in Age-related Macular Degeneration (HiPED)

High Dose Lucentis for Persistent Pigment Epithelial Detachment in Neovascular Age-related Macular Degeneration - The HiPED Study

In this fifth year of anti-VEGF therapy for neovascular AMD, retinal physicians are collecting groups of patients who either do not or only partially respond to anti-VEGF therapy. This study will evaluate the efficacy and safety of 2mg ranibizumab specifically for patients with fibrovascular PEDs that have not resolved following at least 6 consecutive injections of ranibizumab or bevacizumab over the previous 12 months. The investigators hypothesize that the 2mg dose will be able to completely eliminate the persistent PEDS in these patients.

Study Overview

• Status: Terminated
• Conditions: Macular Degeneration; Wet Macular Degeneration; Retinal Pigment Epithelial Detachment
• Intervention / Treatment: Drug: ranibizumab; Drug: ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • Pacific Eye Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age > 50 years
• Active or recurrent neovascular age-related macular degeneration involving the fovea on FA
• Presence of persistent fibrovascular pigment epithelial detachment on OCT following a minimum 6 previous treatments in previous 12 months with ranibizumab and/or bevacizumab. Patients may have received more than 12 months of anti-VEGF therapy.
• ETDRS Best Corrected Visual acuity 20/32 - 20/400

Exclusion Criteria:

• Prior treatment with verteporfin, or external-beam radiation therapy, or transpupillary thermotherapy, Previous subfoveal focal laser photocoagulation involving the foveal center, History of vitrectomy, submacular surgery, or other surgical intervention for AMD, Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals) in study eye.
• Lesion Characteristics: Subfoveal fibrosis or atrophy in study eye, CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.
• Concurrent Ocular Conditions: Concurrent eye disease in the study eye that could compromise visual acuity (e.g., diabetic retinopathy, advanced glaucoma), Any concurrent intraocular condition in the study eye (e.g., diabetic retinopathy or glaucoma) that, in the opinion of the investigator, could either, Require medical or surgical intervention during the 12-month study period to prevent or treat visual loss that might result from that condition, or If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 12-month study period, Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye
• Current vitreous hemorrhage in the study eye
• History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
• Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
• Aphakia or absence of the posterior capsule in the study eye unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure 30 mmHg despite treatment with anti-glaucoma medication)

Concurrent Systemic Conditions

• Pregnancy or premenopausal women not using adequate contraception The following are considered effective means of contraception: surgical sterilization; 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.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications

Other

• Inability to dilate pupils sufficient for adequate fluorescein angiography
• Inability to comply with study or follow up procedures

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

• Pregnancy (positive pregnancy test)
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1 - 2mg ranibizumab monthly; 2mg ranibizumab monthly	Drug: ranibizumab; 2mg intravitreal injection monthly; Drug: ranibizumab; 2mg monthly x 3 doses, then as needed based on recurrence of activity on OCT
ACTIVE_COMPARATOR: Group 2 - 2mg x 3 then PRN	Drug: ranibizumab; 2mg intravitreal injection monthly; Drug: ranibizumab; 2mg monthly x 3 doses, then as needed based on recurrence of activity on OCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in visual acuity from baseline to 24 months	Best corrected visual acuity on the ETDRS chart at 4 meters will be compared	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity from baseline to 6 months	BCVA on ETDRS will be compared from baseline to 6 months	6 months
Safety	incidence and severity of ocular and non-ocular adverse events will be evaluated through 12 months	12 months
% with > 15 ETDRS letter gain from baseline through 12 months		12 months
Change in OCT CST from baseline through 6 and 12 months		12 months
Time to recurrence of PED in PRN Arm		12 months

Collaborators and Investigators

• Sponsor: Anne Fung MD
• Collaborators: Genentech, Inc.

Publications and helpful links

Helpful Links

• Pacific Eye Associates
• Tennessee Retina
• Retina Associates of Kentucky

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: August 24, 2010
• First Submitted That Met QC Criteria: August 25, 2010
• First Posted (ESTIMATE): August 26, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: macular degeneration; ranibizumab; PED; Wet macular degeneration; Retinal Pigment Epithelial Detachment
• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Retinal Detachment; Dissociative Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: FVF4928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Presented at medical conferences, manuscript in preparation