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Age-related Macular DegenerationPhase 3HARBORNCT00891735

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

A Phase 3 study testing Ranibizumab in people with Age-related Macular Degeneration, run by Genentech, Inc. at 99 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Age-related Macular Degeneration
What is being tested?
Ranibizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,097 participants
Where
99 sitesUnited States
Study dates
Jul 2009to Aug 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Ocular Inclusion Criteria (Study Eye)
  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.
  • Active malignancy.
  • History of allergy to fluorescein, not amenable to treatment.
  • Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals).

Trial locations and contacts

99 sites in 1 country.

99 sites in 1 country

United States99 sites

  • Study site

    ‘Aiea, Hawaii, 96701

  • Study site

    Abilene, Texas, 79606

  • Study site

    Altamonte Springs, Florida, 32701

  • Study site

    Arcadia, California, 91007

  • Study site

    Asheville, North Carolina, 28803

  • Study site

    Augusta, Georgia, 30909

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Austin, Texas, 78705

  • Study site

    Baltimore, Maryland, 21287

  • Study site

    Beachwood, Ohio, 44122

  • Study site

    Beverly Hills, California, 90211

  • Study site

    Boston, Massachusetts, 02111

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Boynton Beach, Florida, 33426

  • Study site

    Camp Hill, Pennsylvania, 17011

  • Study site

    Campbell, California, 95008

  • Study site

    Casper, Wyoming, 82601

  • Study site

    Charlotte, North Carolina, 28210

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Chico, California, 95973

  • Study site

    Cincinnati, Ohio, 45242

  • Study site

    Colorado Springs, Colorado, 80909

  • Study site

    Columbus, Ohio, 43212

  • Study site

    Danbury, Connecticut, 06810

  • Study site

    DeSoto, Texas, 75115

  • Study site

    Edina, Minnesota, 55435

  • Study site

    Fort Lauderdale, Florida, 33334

  • Study site

    Fort Myers, Florida, 33912

  • Study site

    Golden, Colorado, 80401

  • Study site

    Great Neck, New York, 11021

  • Study site

    Greenville, South Carolina, 29605

  • Study site

    Hagerstown, Maryland, 21740

  • Study site

    Hamden, Connecticut, 06518

  • Study site

    Houston, Texas, 77030

  • Study site

    Huntingdon Valley, Pennsylvania, 19006

  • Study site

    Indianapolis, Indiana, 46290

  • Study site

    Jackson, Michigan, 49201

  • Study site

    Johnstown, Pennsylvania, 15904

  • Study site

    La Jolla, California, 92093-0946

  • Study site

    Ladson, South Carolina, 29456

  • Study site

    Las Vegas, Nevada, 89144

  • Study site

    Lawrenceville, New Jersey, 08648

  • Study site

    Lexington, Kentucky, 40509

  • Study site

    Lincoln, Nebraska, 68506

  • Study site

    Los Angeles, California, 90033

  • Study site

    Los Angeles, California, 90095-7000

  • Study site

    Lynbrook, New York, 11563

  • Study site

    McAllen, Texas, 78503

  • Study site

    Milwaukee, Wisconsin, 53226

  • Study site

    Mountain View, California, 94040

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New Brunswick, New Jersey, 08901

  • Study site

    New Haven, Connecticut, 06510

  • Study site

    New London, Connecticut, 06320

  • Study site

    New York, New York, 10021

  • Study site

    Northfield, New Jersey, 08225

  • Study site

    Oak Park, Illinois, 60304

  • Study site

    Oakland, California, 94609

  • Study site

    Paducah, Kentucky, 42001

  • Study site

    Palm Beach Gardens, Florida, 33410

  • Study site

    Palm Desert, California, 92211

  • Study site

    Pensacola, Florida, 32503

  • Study site

    Philadelphia, Pennsylvania, 19107

  • Study site

    Phoenix, Arizona, 85020

  • Study site

    Pittsburgh, Pennsylvania, 15212

  • Study site

    Pittsburgh, Pennsylvania, 15213

  • Study site

    Portland, Maine, 04102

  • Study site

    Portland, Oregon, 97210

  • Study site

    Poway, California, 92064

  • Study site

    Rapid City, South Dakota, 57701

  • Study site

    Richmond, Virginia, 23235

  • Study site

    Rochester, New York, 14620

  • Study site

    Sacramento, California, 95817

  • Study site

    Salt Lake City, Utah, 84107

  • Study site

    San Antonio, Texas, 78240

  • Study site

    San Francisco, California, 94107

  • Study site

    San Francisco, California, 94115

  • Study site

    Santa Ana, California, 92705

  • Study site

    Santa Barbara, California, 93103

  • Study site

    Shawnee Mission, Kansas, 66204

  • Study site

    Shirley, New York, 11967

  • Study site

    St Louis, Missouri, 63144

  • Study site

    Stuart, Florida, 34994

  • Study site

    Tampa, Florida, 33609

  • Study site

    Tampa, Florida, 33612

  • Study site

    Teaneck, New Jersey, 07666

  • Study site

    Temple, Texas, 76508

  • Study site

    The Woodlands, Texas, 77384

  • Study site

    Torrance, California, 90503

  • Study site

    Tucson, Arizona, 85704

  • Study site

    Vauxhall, New Jersey, 07088

  • Study site

    Ventura, California, 93003

  • Study site

    Virginia Beach, Virginia, 23454

  • Study site

    West Columbia, South Carolina, 29169

  • Study site

    West Mifflin, Pennsylvania, 15122

  • Study site

    Westlake Village, California, 91361

  • Study site

    Wichita, Kansas, 67214

  • Study site

    Winter Haven, Florida, 33880

  • Study site

    Worcester, Massachusetts, 01605

Other trials in United States

About this study

Official title: A Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis (PRN) in Patients With Subfoveal Neovascular Age-related Macular Degeneration

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.

Being tested
Ranibizumab
Keywords
Lucentis, AMD, Age-related macular degeneration, Subfoveal neovascular age-related macular degeneration, Wet AMD, Macular degeneration, Ranibizumab
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanibizumabDrug

    Also called Lucentis

    Sterile solution for intravitreal injection.

Study groups in NCT00891735
Study groupRoleWhat they receive
Ranibizumab 0.5 mg monthlyExperimentalPatients received ranibizumab 0.5 mg monthly administered intravitreally for 24 months.
Receives: Drug: Ranibizumab
Ranibizumab 2.0 mg monthlyExperimentalPatients received ranibizumab 2.0 mg monthly administered intravitreally for 24 months.
Receives: Drug: Ranibizumab
Ranibizumab 0.5 mg as-needed (pro re nata [PRN])ExperimentalPatients 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.
Receives: Drug: Ranibizumab
Ranibizumab 2.0 mg as-needed (pro re nata [PRN])ExperimentalPatients 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.
Receives: Drug: Ranibizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Month 12

Secondary outcomes (7)

  1. Number of Ranibizumab Injections up to But Not Including Month 12

    Measured: Baseline to Month 12

  2. Percentage of Patients Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) From Baseline 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. An increase in the BCVA score indicates an improvement of vision.

    Measured: Baseline to Month 12

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

    VA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 is 14 lines correctly read in the EDTRS chart.

    Measured: Month 12

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

    The presence of fluid from choroidal neovascularization (CNV) was assessed by spectral domain optical coherence tomography (SD-OCT). No evidence of fluid was defined as no subretinal fluid thickness, no cystoid spaces, no intraretinal fluid, no pigment epithelial defect thickness, and average central subfield thickness < 270 µm.

    Measured: Month 12

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

    Central foveal thickness was assessed by spectral domain optical coherence tomography (SD-OCT).

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

  6. Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

    Macular volume was assessed by spectral domain optical coherence tomography (SD-OCT).

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

  7. Change From Baseline in the Total Area of Choroidal Neovascularization (CNV) and Choroidal Neovascular Leakage at Month 12

    The total area of choroidal neovascularization (CNV) and choroidal neovascular leakage was assessed with fluorescein angiography (FA). Area was measured in disc area units; 1 disc area unit = 2.54 mm^2.

    Measured: Baseline to Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionAug 2011
  4. Study completionAug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,097 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00891735
Sponsor's protocol ID
FVF4579g
Other IDs
GX01511
Acronym
HARBOR
Status last verified
Dec 2012
First submitted
29 Apr 2009
Last updated
18 Jan 2013

Publications

  • 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.

    PubMed 39287532

  • 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.

    PubMed 37079518

  • 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.

    PubMed 36729084

  • 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.

    PubMed 36372347

  • 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.

    PubMed 35654363

  • 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.

    PubMed 35342822

  • 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.

    PubMed 35239009

  • 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.

    PubMed 34934034

  • 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.

    PubMed 34289338

  • 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.

    PubMed 33331859

  • 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.

    PubMed 32402555

  • 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.

    PubMed 32387055

  • 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.

    PubMed 32374423

  • 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.

    PubMed 32353536

  • 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.

    PubMed 31735634

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab in people with Age-related Macular Degeneration, run by Genentech, Inc. at 99 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 99 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00891735, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2013.

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