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

Genentech

Status and phase: Completed; Phase 3

Conditions: Age-related Macular Degeneration

Treatments: Drug: Ranibizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00891735

FVF4579g

GX01511 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 1,097 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,097 participants in 4 patient groups

Ranibizumab 0.5 mg monthly

Experimental group

Description:

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

Treatment:

Drug: Ranibizumab

Ranibizumab 2.0 mg monthly

Experimental group

Description:

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

Treatment:

Drug: Ranibizumab

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

Experimental group

Description:

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.

Treatment:

Drug: Ranibizumab

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

Experimental group

Description:

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.

Treatment:

Drug: Ranibizumab