Clinical trial NCT00284089: Safety and Efficacy of Ranibizumab in Japanese Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration
Official title: Open-label Multicenter, Phase I/II Study Assessing the Safety and Efficacy of Ranibizumab (RFB002) in Japanese Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Subfoveal Choroidal Neovascularization(CNV) Secondary to Age-related Macular Degeneration (AMD)
Keywords: Subfoveal CNV, AMD, ranibizumab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-01-31
Enrollment: 88
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Open-label Multicenter, Phase I/II Study comprising three phases (single dose, multiple dose and extension phase), Assessing the Safety and Efficacy of Ranibizumab (RFB002) in Japanese Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD).

Detailed description: The safety and tolerability of single intravitreal injections of ranibizumab was evaluated in patients enrolled in the single dose phase (Group A). Patients who successfully completed the single dose phase (i.e. did not experience a grade-3 targeted adverse event) could enter the multiple dose phase and receive ranibizumab injections for an additional 11 months. Simultaneously, the multiple dose phase was initiated in two parallel dose groups of additional patients (Group B), who received ranibizumab injections for 12 months. After patients in Group A and Group B had completed the multiple dose phase, all patients who provided written consent and were considered eligible based on the inclusion and exclusion criteria of the extension phase had the opportunity to continue on study treatment with the individualized flexible treatment regimen guided by monthly acuity scores and other ophthalmic examinations until approval of ranibizumab in Japan.

Eligibility criteria: Inclusion Criteria

1. Male or female patients 50 years of age or greater
2. Patients with primary or recurrent subfoveal CNV secondary to AMD
3. Patients who have a BCVA score between 73 and 24 letters in the study eye using ETDRS-like grading charts (approximately 20/40 to 20/320)

Exclusion Criteria

1. No prior treatment in the study eye with verteporfin, external-beam radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, or transpupillary thermotherapy

Extension Phase

Inclusion criteria:

1. Personally provided written informed consent to participate in the extension phase.
2. Patients with subfoveal CNV secondary to AMD who had completed the multiple dose phase in either of the ranibizumab groups (Group A or B).
3. Patients could participate in the extension phase even if they failed to do so on the day of the exit visit in the multiple dose phase (Group A and B), regardless of the time elapsed until the participation in the extension phase.

Exclusion criteria:

1. Received anti-angiogenic drugs (bevacizumab, pegaptanib, ranibizumab, anecortave acetate, corticosteroids or protein kinase C inhibitors, etc.) or
2. Participated in any clinical study of an investigational drug other than this one during the period between the exit visit of the multiple dose phase and the start in the extension phase, if they failed to be enrolled into the extension on the day of the exit visit. Patients were to be excluded even when the fellow eye was treated with any of these drugs.

Primary outcomes:
measure: Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
timeFrame: Baseline and Month 12
measure: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
timeFrame: Baseline, Month 6 and Month 12
measure: Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
timeFrame: Month 12 (start of extension phase) and last visit of extension phase. Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
measure: Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
timeFrame: Baseline and last visit of extension phase - Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
measure: Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
timeFrame: Baseline, Months 3, 6, 9 and 12
measure: Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
timeFrame: Baseline, Months 3, 6, 9 and 12
measure: Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
timeFrame: Months 3, 6, 9 and 12
measure: Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
timeFrame: Baseline, Months 3, 6, 9 and 12
measure: Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
timeFrame: Baseline, Months 3, 6, 9 and 12
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Novartis
Study officials:
affiliation: Novartis
name: Novartis Customer Information
role: STUDY_CHAIR
References:
citation: Tano Y, Ohji M; EXTEND-I Study Group. EXTEND-I: safety and efficacy of ranibizumab in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Acta Ophthalmol. 2010 May;88(3):309-16. doi: 10.1111/j.1755-3768.2009.01843.x. Epub 2010 Feb 16.
citation: Tano Y, Ohji M; EXTEND-I Study Group. Long-term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age-related macular degeneration in the EXTEND-I study. Acta Ophthalmol. 2011 May;89(3):208-17. doi: 10.1111/j.1755-3768.2010.02065.x. Epub 2011 Jan 14.