Safety and Efficacy of Ranibizumab in Japanese Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration

• ClinicalTrials.gov Identifier: NCT00284089
• Recruitment Status: Completed
• First Posted: January 31, 2006
• Results First Posted: February 11, 2011
• Last Update Posted: February 24, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Tracking Information

• First Submitted Date: January 30, 2006
• First Posted Date: January 31, 2006
• Results First Submitted Date: January 20, 2011
• Results First Posted Date: February 11, 2011
• Last Update Posted Date: February 24, 2011
• Study Start Date: April 2005
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2011)

Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B [ Time Frame: Baseline and Month 6 ]

The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 22, 2011)

• Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B [ Time Frame: Baseline and Month 12 ]
  The efficacy assessment was based on Group B patients. BCVA was assessed during all study visits using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
• Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B [ Time Frame: Baseline, Month 6 and Month 12 ]
  BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters.
• 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. [ Time Frame: 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. ]
  Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
• Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B [ Time Frame: 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. ]
  BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The following categories were evaluated:

  • Participants with a BCVA score loss of fewer than 15 letters from baseline at Last Visit
  • Participants with a BCVA score loss of 30 or more letters from baseline at Last Visit
  • Participants with a BCVA score gain of 15 or more letters from baseline at Last Visit
  • Participants with a BCVA score of less than 34 letters at Last Visit
• Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B [ Time Frame: Baseline, Months 3, 6, 9 and 12 ]
  Choroidal Neovascularization was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The area of Choroidal Neovascularization is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm^2 on the retina).
• Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B [ Time Frame: Baseline, Months 3, 6, 9 and 12 ]
  Area of leakage from CNV plus staining of retinal pigment epithelium was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The total area is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm^2 on the retina).
• Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. [ Time Frame: Months 3, 6, 9 and 12 ]
  Area of leakage was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed at the central reading center.
• Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B [ Time Frame: Baseline, Months 3, 6, 9 and 12 ]
  Foveal retinal thickness was assessed by Optical Coherence Tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
• Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B [ Time Frame: Baseline, Months 3, 6, 9 and 12 ]
  Total retinal volume was assessed by Optical Coherence tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Subfoveal Choroidal Neovascularization(CNV) Secondary to Age-related Macular Degeneration (AMD)

Intervention

Drug: Ranibizumab

Ranibizumab was administered by intravitreal injection in the study eye. Intravitreal injection was performed by the investigator following slitlamp examination.

Other Name: Lucentis

Study Arms

• Experimental: Group A: Ranibizumab 0.3 mg
  In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years.
  Intervention: Drug: Ranibizumab
• Experimental: Group A: Ranibizumab 0.5 mg
  In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years.
  Intervention: Drug: Ranibizumab
• Experimental: Group B: Ranibizumab 0.3 mg
  Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
  Intervention: Drug: Ranibizumab
• Experimental: Group B: Ranibizumab 0.5 mg
  Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
  Intervention: Drug: Ranibizumab

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 14, 2010): 88
• Original Enrollment: Not Provided
• Actual Study Completion Date: January 2009
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00284089
• Other Study ID Numbers: CRFB002A1201
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: External Affairs, Novartis Pharmaceuticals
• Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Chair: Novartis Customer Information; Novartis

• PRS Account: Novartis
• Verification Date: February 2011