Efficacy and Safety of Ranibizumab 0.5 vs Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM) Clinical Trial

— Brilliance  

Official title:

A 12-month, Phase III, Randomized, Double-masked, Multicenter, Active-controlled Study to Evaluate the Efficacy and Safety of Two Individualized Regimens of 0.5mg Ranibizumab vs. Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01922102
• Other study ID #: CRFB002F2302
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2013
• Est. completion date: September 14, 2016

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was designed to evaluate the efficacy and safety of two different dosing regimens of 0.5 mg ranibizumab given as intravitreal injection in comparison to verteporfin PDT in patients with visual impairment due to choroidal neovascularization secondary to pathologic myopia (PM)

Description:

This was a phase III, multi-center, randomized, double-masked, active-controlled study comparing 0.5 mg ranibizumab vs. vPDT therapy. The study included 15 scheduled visits over 12 months, and there were to be two additional visits (2a, 3a) for subset of patients in whom PK analysis were performed.

There were 3 periods in this study: Screening period-from Day -14 to Baseline; Treatment period-from Baseline to Month 11; Follow-up period-from Month 11 to Month 12 Patients entered the 11 months Treatment period at Visit 2 (Day 1) if eligibility criteria were met and were randomized in three treatment groups Group I ranibizumab 0.5 mg driven by VA stability criteria or Group II ranibizumab 0.5 mg driven by disease activity criteria or Group III vPDT (randomization ratio of 2:2:1) and received first treatment of either a ranibizumab injection and sham vPDT or sham injection and active vPDT and will return to the clinical center within 7 days to undergo safety assessments as well as assessments of the effect of treatment by the evaluating investigator. The following visits were performed at one month intervals starting at Visit 4 and continuing through Visit 14. At all monthly visits (at/from Month 2 for group I, at/from Month 1 for group II and at/from Month 3 for group III) the decision for treatment were made by the evaluating investigator based on the VA stability criteria and on the disease activity criteria. At Month 3 (visit 6) and at all following monthly visits for all three groups one of the three options can recommended by evaluating investigator: a) ranibizumab 0.5 mg, b) ranibizumab 0.5 mg + vPDT; c) vPDT. The treating investigator were then perform treatment based on randomization and masking requirements.

At each monthly visit, patients had a safety evaluation by the evaluating investigator prior to study treatment, consisting of visual acuity measurements, ophthalmic examinations and evaluation of adverse events and vital signs. Routine hematology, chemistry, and urinalysis profiles were obtained at Visit 6, 9 and 12 (Month 3, 6 and 9). At Month 12 several procedures and assessments were performed which are required at study completion visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 457
• Est. completion date: September 14, 2016
• Est. primary completion date: September 14, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Visual impairment due to CNV secondary to PM.

• Best corrected visual acuity in the study eye > 24 and < 78 ETDRS letters.

• High myopia (> -6D),

• anterio-posterior elongation > 26 mm; posterior changes compatible with the pathologic myopia.

• Either CNV locations in the study eye: subfoveal, juxtafoveal, extrafoveal.

Exclusion Criteria:

• Some preexisting eye disorders or systemic diseases;-Blood pressure > 150/90 mmHg

• Prior focal/grid laser to the macular area -History of treatment with any anti-VEGF or verteporfin PDT in the study eye

• Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye

Related Conditions & MeSH terms

• Choroidal Neovascularization
• Myopia
• Neoplasm Metastasis
• Neovascularization, Pathologic
• Vision Disorders
• Vision, Low
• Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)

Intervention

Drug:
• Ranibizumab 0.5mg
0.5 mg ranibizumab (intravitreal injections)
• Ranibizumab 0.5 mg
0.5 mg ranibizumab (intravitreal injections)
• Verteporfin PDT
Verteporfin for intravenous injection delivered by intravenous infusion followed by the light application

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Qingdao	Shandong
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shantou	Guangdong
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Tianjin	Tianjin
China	Novartis Investigative Site	Wenzhou	Zhejiang
China	Novartis Investigative Site	Wu XI	Jiangsu
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xi'an	Shanxi
Hong Kong	Novartis Investigative Site	Hongkong
India	Novartis Investigative Site	Angamaly
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bhubaneswar	Orissa
India	Novartis Investigative Site	Chandigarh	Haryana
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Vanchiyoor	Kerala
Korea, Republic of	Novartis Investigative Site	Pusan
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Manila	Metro Manila
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Nakornphathom

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Hong Kong,  India,  Korea, Republic of,  Philippines,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3	Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.	From Baseline to Month 3
Secondary	Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6	Best corrected visual acuity (BCVA) was tested using the early treatment diabetic retinopathy study (ETDRS) VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.; Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 6.	From Baseline to Month 6
Secondary	The Average Change in BCVA Score From Baseline to Month 1 Through Month 12	Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.; Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 12	From Baseline to Month 12
Secondary	Mean Change From Baseline in Visual Acuity Over Time	Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.	Change from baseline at months 3, 6, and 12
Secondary	Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye	ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.	From Baseline to Month 12
Secondary	Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT)	Central sub-field thickness (CSFT) is a variable assessed via Optical Coherence Tomography (OCT). OCT was performed prior to any study drug administration to assess presence of intra, subretinal fluid, or increase of CSFT.	Baseline, Month 3, Month 6, and Month 12
Secondary	Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12	CNV leakage is assessed via fluorescein angiography (center involvement) category: definite, questionable, absent, can't grade, and missing.	From Baseline until Month 12
Secondary	NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12	The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.	Change from baseline at month 3, 6 and 12
Secondary	Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups	To assess treatment pattern with ranibizumab	From Baseline to Month 12