A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-related Macular Degeneration (HARBOR)

NCT00891735 | Completed Phase 3 Results

• 2 other identifiers: FVF4579gGX01511
• Study Type: interventional
• Target: 1,097
• Locations: 1 country
• Sites: 99

Brief Summary

This is a Phase III, multicenter, randomized, double-masked, dose-comparison study of the efficacy and safety of ranibizumab injection administered intravitreally to patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Results are presented for the first 12 months of the study.

Conditions

Age-related Macular Degeneration

Keywords

Lucentis; AMD; Age-related macular degeneration; Subfoveal neovascular age-related macular degeneration; Wet AMD; Macular degeneration; Ranibizumab

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12

  BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. A decrease in the BCVA score indicates a worsening of vision. A positive change score indicates improvement.

  Baseline to Month 12

Secondary Outcomes (7)

• Number of Ranibizumab Injections up to But Not Including Month 12

  Baseline to Month 12

• Percentage of Patients Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Month 12

  Baseline to Month 12

• Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Month 12

  Month 12

• Percentage of Patients With no Evidence of Fluid From Choroidal Neovascularization (CNV) at Month 12

  Month 12

• Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

  Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

Study Arms (4)

Ranibizumab 0.5 mg monthly

EXPERIMENTAL

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 24 months.

Drug: Ranibizumab

Ranibizumab 2.0 mg monthly

EXPERIMENTAL

Patients received ranibizumab 2.0 mg monthly administered intravitreally for 24 months.

Drug: Ranibizumab

Ranibizumab 0.5 mg as-needed (pro re nata [PRN])

EXPERIMENTAL

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.

Drug: Ranibizumab

Ranibizumab 2.0 mg as-needed (pro re nata [PRN])

EXPERIMENTAL

Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 21 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.

Drug: Ranibizumab

Interventions

Ranibizumab DRUG

Sterile solution for intravitreal injection.

Also known as: Lucentis

Ranibizumab 0.5 mg as-needed (pro re nata [PRN]); Ranibizumab 0.5 mg monthly; Ranibizumab 2.0 mg as-needed (pro re nata [PRN]); Ranibizumab 2.0 mg monthly

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For sexually active women of childbearing potential, agreement to the use of an appropriate form of contraception (or abstinence) for the duration of the study.
• Best corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, of 20/40-20/320 (Snellen equivalent).
• Choroidal neovascularization (CNV) lesions with classic CNV component, occult CNV, or with some classic CNV component were permissible.
• Total area of lesion \< 12 disc area or 30.48 mm\^2.

You may not qualify if:

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for age-related macular degeneration (AMD) in the study eye.
• Prior treatment with Visudyne(R), external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye.
• Previous intravitreal drug delivery (eg, intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation) in the study eye.
• Previous treatment or participation in a clinical trial involving anti-angiogenic drugs (Avastin(R), anecortave acetate, protein kinase C inhibitors, etc), in the non-study eye within 3 months of Day 0 (first day of treatment). The patient may not have received Lucentis(R) or Macugen(R) in the non-study eye within 7 days of Day 0.
• Treatment with Visudyne(R) in the non-study eye \< 7 days preceding Day 0.
• Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \> 50% of the total area of the lesion or \> 1 disc area (2.54 mm\^2) in size.
• Subfoveal fibrosis or atrophy in the study eye.
• CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.
• Retinal pigment epithelial tear involving the macula in the study eye.
• Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could either: Require medical or surgical intervention during the 24-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 (BCVA) over the 24-month study period.
• Uncontrolled blood pressure.
• Atrial fibrillation not managed by patient's primary care physician or cardiologist within 3 months of screening visit.
• History of stroke within the last 3 months of screening visit.
• 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 renders the patient at high risk for treatment complications.
• Current treatment for active systemic infection.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (99)

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Phoenix, Arizona, 85020, United States

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Tucson, Arizona, 85704, United States

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Arcadia, California, 91007, United States

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Beverly Hills, California, 90211, United States

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Campbell, California, 95008, United States

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Chico, California, 95973, United States

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La Jolla, California, 92093-0946, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90095-7000, United States

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Mountain View, California, 94040, United States

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Oakland, California, 94609, United States

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Palm Desert, California, 92211, United States

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Poway, California, 92064, United States

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Sacramento, California, 95817, United States

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San Francisco, California, 94107, United States

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San Francisco, California, 94115, United States

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Santa Ana, California, 92705, United States

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Santa Barbara, California, 93103, United States

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Torrance, California, 90503, United States

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Ventura, California, 93003, United States

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Westlake Village, California, 91361, United States

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Aurora, Colorado, 80045, United States

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Colorado Springs, Colorado, 80909, United States

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Golden, Colorado, 80401, United States

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Danbury, Connecticut, 06810, United States

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Hamden, Connecticut, 06518, United States

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New Haven, Connecticut, 06510, United States

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New London, Connecticut, 06320, United States

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Altamonte Springs, Florida, 32701, United States

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Boynton Beach, Florida, 33426, United States

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Fort Lauderdale, Florida, 33334, United States

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Fort Myers, Florida, 33912, United States

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Palm Beach Gardens, Florida, 33410, United States

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Pensacola, Florida, 32503, United States

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Stuart, Florida, 34994, United States

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Tampa, Florida, 33609, United States

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Tampa, Florida, 33612, United States

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Winter Haven, Florida, 33880, United States

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Augusta, Georgia, 30909, United States

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‘Aiea, Hawaii, 96701, United States

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Chicago, Illinois, 60637, United States

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Oak Park, Illinois, 60304, United States

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Indianapolis, Indiana, 46290, United States

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Shawnee Mission, Kansas, 66204, United States

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Wichita, Kansas, 67214, United States

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Lexington, Kentucky, 40509, United States

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Paducah, Kentucky, 42001, United States

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Portland, Maine, 04102, United States

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Baltimore, Maryland, 21287, United States

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Hagerstown, Maryland, 21740, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02114, United States

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Worcester, Massachusetts, 01605, United States

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Jackson, Michigan, 49201, United States

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Edina, Minnesota, 55435, United States

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St Louis, Missouri, 63144, United States

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Lincoln, Nebraska, 68506, United States

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Las Vegas, Nevada, 89144, United States

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Lawrenceville, New Jersey, 08648, United States

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New Brunswick, New Jersey, 08901, United States

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Northfield, New Jersey, 08225, United States

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Teaneck, New Jersey, 07666, United States

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Vauxhall, New Jersey, 07088, United States

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Great Neck, New York, 11021, United States

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Lynbrook, New York, 11563, United States

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New York, New York, 10021, United States

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Rochester, New York, 14620, United States

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Shirley, New York, 11967, United States

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Asheville, North Carolina, 28803, United States

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Charlotte, North Carolina, 28210, United States

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Beachwood, Ohio, 44122, United States

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Cincinnati, Ohio, 45242, United States

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Columbus, Ohio, 43212, United States

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Portland, Oregon, 97210, United States

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Camp Hill, Pennsylvania, 17011, United States

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Huntingdon Valley, Pennsylvania, 19006, United States

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Johnstown, Pennsylvania, 15904, United States

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Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Pittsburgh, Pennsylvania, 15213, United States

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West Mifflin, Pennsylvania, 15122, United States

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Greenville, South Carolina, 29605, United States

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Ladson, South Carolina, 29456, United States

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West Columbia, South Carolina, 29169, United States

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Rapid City, South Dakota, 57701, United States

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Nashville, Tennessee, 37203, United States

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Abilene, Texas, 79606, United States

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Austin, Texas, 78705, United States

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DeSoto, Texas, 75115, United States

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Houston, Texas, 77030, United States

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McAllen, Texas, 78503, United States

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San Antonio, Texas, 78240, United States

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Temple, Texas, 76508, United States

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The Woodlands, Texas, 77384, United States

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Salt Lake City, Utah, 84107, United States

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Richmond, Virginia, 23235, United States

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Virginia Beach, Virginia, 23454, United States

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Milwaukee, Wisconsin, 53226, United States

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Casper, Wyoming, 82601, United States

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Related Publications (21)

• Tong N, Fan W, Su L, Ebraheem A, Uji A, Marion K, Sadda S. RELATIONSHIP BETWEEN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS AND NUMBER OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE HARBOR STUDY. Retina. 2024 Oct 1;44(10):1696-1703. doi: 10.1097/IAE.0000000000004171.

  PMID: 39287532 DERIVED

• Kim S, Stockwell A, Qin H, Gao SS, Sagolla M, Stoilov I, Wuster A, Lai P, Yaspan BL, Jeanne M. Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects. PLoS One. 2023 Apr 20;18(4):e0280484. doi: 10.1371/journal.pone.0280484. eCollection 2023.

  PMID: 37079518 DERIVED

• Adrean SD, Chaili S, Hill L, Amador-Patarroyo MJ. PATTERNS OF SUBRETINAL AND/OR INTRARETINAL FLUID RECURRENCE IN PATIENTS WHO RECEIVED AS-NEEDED RANIBIZUMAB THERAPY IN THE HARBOR TRIAL. Retina. 2023 Apr 1;43(4):624-631. doi: 10.1097/IAE.0000000000003708. Epub 2022 Dec 21.

  PMID: 36729084 DERIVED

• Staurenghi G, Cozzi M, Sadda S, Hill L, Gune S. Characteristics that Correlate with Macular Atrophy in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023 Apr;7(4):300-306. doi: 10.1016/j.oret.2022.11.002. Epub 2022 Nov 11.

  PMID: 36372347 DERIVED

• Lally DR, Hill L, Amador-Patarroyo MJ. Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis. Ophthalmol Retina. 2022 Nov;6(11):1054-1060. doi: 10.1016/j.oret.2022.05.026. Epub 2022 May 30.

  PMID: 35654363 DERIVED

• Sheth V, D'Rozario M, Gune S, Blotner S. Fluctuations in central foveal thickness and association with vision outcomes with anti-VEGF therapy for nAMD: HARBOR post hoc analysis. BMJ Open Ophthalmol. 2022 Mar 9;7(1):e000957. doi: 10.1136/bmjophth-2021-000957. eCollection 2022.

  PMID: 35342822 DERIVED

• Freund KB, Staurenghi G, Jung JJ, Zweifel SA, Cozzi M, Hill L, Blotner S, Tsuboi M, Gune S. Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR. Graefes Arch Clin Exp Ophthalmol. 2022 Aug;260(8):2437-2447. doi: 10.1007/s00417-022-05586-w. Epub 2022 Mar 3.

  PMID: 35239009 DERIVED

• Pawloff M, Bogunovic H, Gruber A, Michl M, Riedl S, Schmidt-Erfurth U. SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES. Retina. 2022 May 1;42(5):831-841. doi: 10.1097/IAE.0000000000003385.

  PMID: 34934034 DERIVED

• Holekamp NM, Sadda S, Sarraf D, Guymer R, Hill L, Blotner S, Spicer G, Gune S. Effect of Residual Retinal Fluid on Visual Function in Ranibizumab-Treated Neovascular Age-Related Macular Degeneration. Am J Ophthalmol. 2022 Jan;233:8-17. doi: 10.1016/j.ajo.2021.06.029. Epub 2021 Jul 18.

  PMID: 34289338 DERIVED

• Javaheri M, Hill L, Ghanekar A, Stoilov I. Changes in Treatment-Naive Pigment Epithelial Detachments Associated With the Initial Anti-Vascular Endothelial Growth Factor Injection: A Post Hoc Analysis From the HARBOR Trial. JAMA Ophthalmol. 2021 Feb 1;139(2):219-223. doi: 10.1001/jamaophthalmol.2020.5130.

  PMID: 33331859 DERIVED

• Sadda SR, Abdelfattah NS, Lei J, Shi Y, Marion KM, Morgenthien E, Gune S, Balasubramanian S. Spectral-Domain OCT Analysis of Risk Factors for Macular Atrophy Development in the HARBOR Study for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020 Oct;127(10):1360-1370. doi: 10.1016/j.ophtha.2020.03.031. Epub 2020 Apr 2.

  PMID: 32402555 DERIVED

• Khurana RN, Chang L, Day BM, Ghanekar A, Stoilov I. Timing of Peak Vision Gains in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab. Ophthalmol Retina. 2020 Aug;4(8):760-766. doi: 10.1016/j.oret.2020.02.011. Epub 2020 Feb 27.

  PMID: 32387055 DERIVED

• Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 May 5;5(5):CD012208. doi: 10.1002/14651858.CD012208.pub2.

  PMID: 32374423 DERIVED

• Khurana RN, Hill L, Ghanekar A, Gune S. Agreement of Spectral-Domain OCT with Fluorescein Leakage in Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the HARBOR Study. Ophthalmol Retina. 2020 Nov;4(11):1054-1058. doi: 10.1016/j.oret.2020.04.016. Epub 2020 Apr 28.

  PMID: 32353536 DERIVED

• Patel Y, Miller DM, Fung AE, Hill LF, Rosenfeld PJ. Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration? Ophthalmol Retina. 2020 Feb;4(2):141-147. doi: 10.1016/j.oret.2019.09.006. Epub 2019 Sep 18.

  PMID: 31735634 DERIVED

• Khurana RN, Chang LK, Hill LF, Ghanekar A, Stoilov I. The Value of Prior Response to Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration: A HARBOR Subanalysis. Ophthalmol Retina. 2020 Jan;4(1):13-18. doi: 10.1016/j.oret.2019.06.008. Epub 2019 Jul 5.

  PMID: 31416763 DERIVED

• Nassisi M, Lei J, Abdelfattah NS, Karamat A, Balasubramanian S, Fan W, Uji A, Marion KM, Baker K, Huang X, Morgenthien E, Sadda SR. OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study. Ophthalmology. 2019 Dec;126(12):1667-1674. doi: 10.1016/j.ophtha.2019.05.016. Epub 2019 May 29.

  PMID: 31281056 DERIVED

• Hallak JA, de Sisternes L, Osborne A, Yaspan B, Rubin DL, Leng T. Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2019 Jul 1;137(7):738-744. doi: 10.1001/jamaophthalmol.2019.0868.

  PMID: 31021381 DERIVED

• Sarraf D, London NJ, Khurana RN, Dugel PU, Gune S, Hill L, Tuomi L. Ranibizumab Treatment for Pigment Epithelial Detachment Secondary to Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the HARBOR Study. Ophthalmology. 2016 Oct;123(10):2213-24. doi: 10.1016/j.ophtha.2016.07.007. Epub 2016 Aug 23.

  PMID: 27566855 DERIVED

• Frenkel RE, Shapiro H, Stoilov I. Predicting vision gains with anti-VEGF therapy in neovascular age-related macular degeneration patients by using low-luminance vision. Br J Ophthalmol. 2016 Aug;100(8):1052-7. doi: 10.1136/bjophthalmol-2015-307575. Epub 2015 Nov 5.

  PMID: 26541435 DERIVED

• Busbee BG, Ho AC, Brown DM, Heier JS, Suner IJ, Li Z, Rubio RG, Lai P; HARBOR Study Group. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013 May;120(5):1046-56. doi: 10.1016/j.ophtha.2012.10.014. Epub 2013 Jan 23.

  PMID: 23352196 DERIVED

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800-821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2009
• First Posted: May 1, 2009
• Study Start: July 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2012
• Last Updated: January 18, 2013
• Results First Posted: January 18, 2013

Record last verified: 2012-12

Locations

US (99)