A Study of the Criteria Establishing the Need for Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia.

Phase 3CompletedNCT02034006

Novartis Pharmaceuticals200 enrolled

Overview

The primary objective of the study was to investigate current criteria driving re-treatment in patients affected by Choroidal Neovascularization (CNV) secondary to Pathologic Myopia (PM) and experiencing a relapse of the disease after the first administration of ranibizumab.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

200

Conditions

Choroidal Neovascularization Secondary to Pathologic Myopia

Interventions

RanibizumabDRUG

All patients received a single initial intravitreal injection of ranibizumab 0.5 mg/0.05 ml as per Committee for Human Medicinal Products (CHMP)approval. Further injections might have been required when monitoring reveals disease activity. Disease activity, defined as reduced visual acuity and/or signs of lesion activity, was evaluated based on clinical examination (BCVA, fundus), and/or optical coherence tomography (OCT), and/or fluorescein angiography (FAG). Bilateral treatment was allowed provided at least 14 days of intercurrence.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

INCLUSION CRITERIA: * Written informed consent given before any study related procedure is performed * Diagnosis of active CNV secondary to PM confirmed by complete ocular examination in the affected eye(s) using the following criteria: * Presence of high myopia greater than -6D of spherical equivalence * Presence of posterior changes compatible with pathologic myopia (any signs of attenuation of retinal pigment epithelium (RPE) and choroids, mottling of the RPE, tilted disc, geographic atrophy of RPE, Fuchs spots, posterior staphyloma, submacular hemorrhage, lacquer cracks) detected by fundus ophthalmoscopy and fundus photography * Presence of active leakage from CNV observed through fluorescein angiography (FAG) * Presence of intra or subretinal fluid demonstrated by Optical Coherence Tomography (OCT) * BCVA \> 24 letters and \< 78 letters tested at 4 meters staring distance using ETDRS-like visual acuity chart * Visual loss must be only due to the presence of any eligible types of CNV related to PM based on clinical ocular findings, FAG and OCT. (Also patients that have for example 20/60 as their best visual acuity due to PM in their history and have additional vision loss due to CNV lesion can be included) EXCLUSION CRITERIA: * Patients with inability to comply with study related procedures * Pregnant or nursing (lactating) women and women of childbearing potential UNLESS using effective contraception during treatment * Presence of confirmed systolic blood pressure \> 150 mmHg or diastolic \> 90 mmHg at the time of enrollment * History of stroke * Any type of advanced, severe or unstable medical condition or its treatment that could significantly bias the assessment of clinical status and interfere with primary and/or secondary outcome evaluations or put the patient at risk * Presence of active infectious disease or intra-ocular inflammation in either eye at the time of enrollment * Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 12-month study period (including retinal detachment, cataract and pre-retinal membrane of the macula) * History of pan-retinal or focal/grid laser photocoagulation with involvement of the macular area in the study eye at any time * History of intraocular treatment with any anti-vascular endothelial growth factor (VEGF), verteporfin photodynamic therapy (vPDT) and any intra-ocular surgery or corticosteroid administration within one month before study entrance * Known hypersensitivity to ranibizumab or any component of the ranibizumab formulation * Simultaneous participation in a study that includes administration of any investigational drug

Locations (31)

Outcomes

Primary Outcomes

Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage

Presence of active leakage on fluorescein angiography (FAG) was assessed at screening (14 to 3 days before baseline visit), month 2 and month 6. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of active leakage (Yes/No). For retreated patients, the presence/absence of active leakage was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Time frame: Screening, Month 2, Month 6

Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema

Presence of macular edema from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of macular edema (Yes/No). For retreated patients, the presence/absence of macular edema was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Time frame: Screening, Month 2, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts

Presence of cysts from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of cysts (Yes/No). For retreated patients, the presence/absence of cysts was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Data from ClinicalTrials.gov

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Novartis Investigative Site

Bari, BA, Italy

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Desenzano del Garda, BS, Italy

Novartis Investigative Site

Bolzano, BZ, Italy

Novartis Investigative Site

Cagliari, CA, Italy

Novartis Investigative Site

Catania, CT, Italy

Novartis Investigative Site

Catanzaro, CZ, Italy

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Rapallo, GE, Italy

...and 21 more locations

Time frame: Screening, Month 2, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid

Presence of Intra-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of Intra-retinal fluid (Yes/No). For retreated patients, the presence/absence of Intra-retinal fluid was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis. \*NE = Not evaluable

Time frame: Screening, Month 2, Month 6, Month 12

Change in Central Subfield Thickness (CSFT)

Central subfield thickness (CSFT) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSFT versus previous visit. For retreated patients, the change in CSFT was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Screening, Month 2, Month 6, Month 12

Change in Central Subfield Volume (CSV)

Central subfield volume (CSV) from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change in CSV versus previous visit. For retreated patients, the change in CSV was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Screening, Month 2, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid

Presence of sub-retinal fluid from optical coherence tomography (OCT) was assessed at screening (14 to 3 days before baseline visit), month 2, month 6 and month 12. The regression model for sub-retinal fluid was not valid because "Yes" was reported in almost all subjects causing a quasi-complete separation of data points. \*NE = Not evaluable

Time frame: Screening, Month 2, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities

Presence of clinically significant abnormalities was assessed at baseline, month 1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of presence of clinically significant abnormalities (Yes/No). For retreated patients, the presence/absence of clinically significant abnormalities was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters

Improvement in BCVA \< 5 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA \< 5 letters (Yes/No) which was reported as Gain \>= 5 letters versus Gain \< 5 letters. For retreated patients, Gain \>= 5 letters and Gain \< 5 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters

Improvement in BCVA \< 10 letters (Yes/No) was assessed at month1, month 2, month 3, month 6 and month 12. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of improvement in BCVA \< 10 letters (Yes/No) which was reported as Gain \>= 10 letters versus Gain \< 10 letters. For retreated patients, Gain \>= 10 letters and Gain \< 10 letters were considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Number of Patients in Different Categories of Changes From Baseline in BCVA

Changes from baseline in BCVA are described for the ETDRS parameter considering the following categories at each assessment: "no change" if the change was equal to 0 letter, "worsening" if change \< 0 letter , "improvement" if change \> 0 letter. A univariate logistic regression model was applied expressing the presence/absence of the first retreatment in function of change from baseline in BCVA (improved/worsened/stable) which was reported as Improved versus no change and worsened versus no change. For retreated patients, this variable was considered at the closest time-point to the first re-treatment: the last scheduled assessment immediately before the first re-treatment was considered. For treated patients, the last scheduled assessment available was considered. In case of missing value on the scheduled assessment, the value was considered as missing for this analysis.

Time frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Secondary Outcomes

Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye

Change from baseline in BCVA (Best Corrected Visual Acuity) was Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. Patients with a BCVA ETDRS letter score of 78 to 24 in the study eye were included; A higher score represents better functioning of the study eye. A positive change from baseline shows improvement.

Time frame: Baseline, Month 6, Month 12

Mean Number of Ranibizumab Injection

Mean number of ranibizumab injection is reported as number of injections per patient.

Time frame: Baseline to Month 12

Time to Re-treatment

Time to re-treatment, defined as time in months from the data of first dose of ranibizumab to the date of re-treatment, was evaluated.

Time frame: Baseline to Month 12

Number of Patients Having Ocular and/or Systemic Adverse Event (AE)

Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported

Time frame: Baseline to Month 12

Change in Patient Quality of Life From Baseline to Month 2 and Month 12

Patient quality of life was assessed by Impact of Vision Impairment (IVI) questionnaire. IVI is a 32-item instrument, either self- or interviewer-administered, developed to measure the impact of vision impairment on daily activities in five domains. The 32 items were divided into 5 domains as follows: Leisure and work (items 1 to 5), Social and consumer interaction (items 6 to 10 and items 23-24), Household and personal care (items 11 to 14 and items 20-21), Mobility (items 15 to 19 and item 22), Emotional reaction to vision loss (items 25 to 32). Responses to the IVI items were rated on a five-category Likert scale: not at all, 0; hardly at all, 1; a little, 2; a fair amount, 3; a lot, 4; and can't do because of eyesight, 5. Total score was an arithmetic average of the items rated between 0 (the best score) and 5 (the worst score). A negative change indicates improvement. Data was computed on items with non missing response

Time frame: Baseline, Month 2, Month 12