Ranibizumab Clinical Trials

What Is Ranibizumab?

Ranibizumab, known by the brand name Lucentis, is an FDA-approved medication for several eye conditions, including diabetic macular edema, retinal vein occlusion, and neovascular (wet) age-related macular degeneration. It is a humanized antibody fragment that works by blocking vascular endothelial growth factor (VEGF).

VEGF is a protein naturally present in the eye that can lead to the growth of abnormal blood vessels and leakage, causing fluid buildup and potential vision loss. By inhibiting VEGF, ranibizumab helps to reduce this vessel leakage and abnormal growth. In addition to its approved indications, ranibizumab is also being investigated for other related eye conditions, such as choroidal neovascularization and diabetic retinopathy. There are currently 480 clinical trials involving ranibizumab, with 11 trials actively recruiting participants. These studies have enrolled a total of 116,974 participants since the first trial began in 2003, with research ongoing until at least 2026.

Uses and Conditions Under Study

Ranibizumab is extensively studied for various eye conditions, primarily those involving abnormal blood vessel growth and fluid leakage in the retina.

• Diabetic Eye Diseases: Ranibizumab is investigated for diabetic macular edema (DME) and diabetic retinopathy. DME is a swelling of the macula, the central part of the retina, caused by leaky blood vessels due to diabetes. Diabetic retinopathy refers to broader damage to the retina from diabetes. Ranibizumab helps by blocking VEGF, which causes vessel leakage in diabetic eye disease. These conditions are being studied in a combined total of 100 trials.
• Age-Related Macular Degeneration (AMD): This is a leading cause of vision loss in older adults, particularly the "wet" form (neovascular AMD), where abnormal blood vessels grow and leak under the retina. Ranibizumab inhibits the growth of these new vessels. Across various forms of macular degeneration, ranibizumab is being studied in approximately 140 trials.
• Macular Edema: This condition involves swelling of the macula due to fluid leakage. Ranibizumab targets the VEGF protein, a key contributor to this leakage. Macular edema is the focus of 42 trials.
• Retinal Vein Occlusion (RVO): RVO occurs when a retinal vein becomes blocked, leading to fluid leakage and macular edema. Ranibizumab is effective in treating macular edema resulting from RVO. There are 26 trials investigating ranibizumab for RVO.
• Choroidal Neovascularization (CNV): CNV involves the growth of abnormal blood vessels in the choroid, often associated with AMD. Ranibizumab helps to inhibit this abnormal vessel growth. This condition is being studied in 28 trials.

Other conditions under investigation include retinopathy of prematurity, uveitic macular edema, and polypoidal choroidal vasculopathy.

Dosing

Ranibizumab is primarily administered as an intravitreal injection, meaning it is injected directly into the eye. It has also been studied in a port delivery system (PDS) implant, which is designed to continuously release the medication over time.

Commonly studied strengths for intravitreal injections include 0.3 mg, 0.5 mg, 1.0 mg, and 2.0 mg. The specific dose and frequency depend on the condition being treated and the patient's response. For instance, some regimens involve an initial "loading phase" of monthly injections, followed by a "treat-and-extend" approach where the interval between injections is gradually lengthened based on disease activity, or a "pro re nata" (PRN) regimen where injections are given as needed.

The port delivery system has been investigated with higher concentrations, such as 10 mg/mL, 40 mg/mL, and 100 mg/mL. While most studies focus on adult eye conditions, ranibizumab is also being explored for conditions like retinopathy of prematurity, which affects infants.

Side Effects

In clinical trials, the most commonly reported side effect for patients taking Ranibizumab was nasopharyngitis (inflammation of the nose and throat), which occurred in 11.7% of patients. This was less frequent than in patients receiving placebo, where it occurred in 15.1%.

Other common side effects observed in patients treated with Ranibizumab, compared to placebo, included:

• Hypertension (high blood pressure): 7.3% of patients on Ranibizumab experienced this, compared to 4.1% on placebo.
• Headache: 5.4% of patients on Ranibizumab experienced headache, compared to 4.1% on placebo.
• Conjunctival haemorrhage (bleeding in the white part of the eye): 5.4% of patients on Ranibizumab experienced this, compared to 3.5% on placebo.
• Urinary tract infection: 5.3% of patients on Ranibizumab experienced this, compared to 12.3% on placebo.
• Cough: 4.8% of patients on Ranibizumab experienced cough, compared to 11.0% on placebo.
• Upper respiratory tract infection: 4.3% of patients on Ranibizumab experienced this, compared to 2.7% on placebo.
• Sinusitis: 4.1% of patients on Ranibizumab experienced this, compared to 1.4% on placebo.

Reduced visual acuity was reported in 4.3% of patients taking Ranibizumab, which was similar to the 4.1% of patients on placebo.

Clinical Trial Results

Clinical trials have evaluated Ranibizumab for various eye conditions, primarily focusing on improving vision and reducing disease activity.

Treatment for Age-related Macular Degeneration (AMD)

In a study (NCT00275821) involving patients with subfoveal choroidal neovascularization (CNV) secondary to AMD, Ranibizumab demonstrated improvements in vision and retinal thickness over 12 months. Patients receiving Ranibizumab 0.3 mg monthly gained an average of 8.3 letters on a vision chart, while those on a 0.3 mg regimen of three monthly doses followed by quarterly doses gained 4.9 letters. Retinal thickness at the central point decreased by an average of 105.3 micrometers with 0.3 mg monthly dosing and 105.6 micrometers with 0.5 mg three monthly doses followed by quarterly doses, indicating a reduction in swelling. Total lesion area also decreased, for example, by 1.28 mm² with 0.3 mg monthly dosing.

Another study in Japanese patients (NCT00284089) for AMD showed similar benefits. At 12 months, patients treated with Ranibizumab 0.3 mg gained an average of 9.5 letters in visual acuity, and those on 0.5 mg gained 10.5 letters. Foveal retinal thickness decreased by an average of 194.0 micrometers with 0.3 mg and 245.4 micrometers with 0.5 mg. Additionally, at 12 months, 35.3% of patients on 0.3 mg and 35.0% on 0.5 mg showed an absence of leakage in the study eye.

A further study (NCT00331864) for AMD also reported visual acuity improvements. Patients in the Ranibizumab Non-ANCHOR group gained an average of 3.6 letters in best-corrected visual acuity at 12 months, and their central retinal thickness decreased by an average of 91.5 micrometers. The average number of treatments in this group was 5.6 treatments over the study period.

In a small trial (NCT00363168) for hemorrhagic CNV, 5 participants on Ranibizumab Dose A and 2 participants on Ranibizumab Dose B avoided a loss of 15 or more letters in best-corrected visual acuity over 12 months.

Treatment for Diabetic Macular Edema (DME)

For patients with diabetic macular edema, a study (NCT00284050) compared Ranibizumab to sham injections. Over 12 months, patients receiving Ranibizumab 0.3 mg experienced an average gain of 11.8 letters in visual acuity, while those on 0.5 mg gained 8.8 letters. In contrast, patients receiving sham injections experienced an average loss of 1.4 letters. Central retinal thickness significantly improved with Ranibizumab treatment, decreasing by an average of 200.7 micrometers for the 0.3 mg dose and 187.6 micrometers for the 0.5 mg dose, compared to a 48.4 micrometer decrease in the sham group.

Currently Recruiting Trials

Where to Participate

• Austin, Texas (8 sites)
• Phoenix, Arizona (8 sites)
• Baltimore, Maryland (7 sites)
• West Columbia, South Carolina (5 sites)
• San Francisco, California (5 sites)
• Sacramento, California (4 sites)
• Salt Lake City, Utah (4 sites)
• Portland, Maine (4 sites)
• Spokane, Washington (4 sites)
• Santa Ana, California (4 sites)

Development Timeline