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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. (OLIMPIC)

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ClinicalTrials.gov Identifier: NCT02034006
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : February 18, 2019
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Choroidal Neovascularization Secondary to Pathologic Myopia Drug: Ranibizumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 12-month, Open-label, Interventional, Multicentre Study to Investigate the Current Criteria Driving Re-treatment With Ranibizumab Upon Relapse in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia
Actual Study Start Date : June 10, 2014
Actual Primary Completion Date : July 15, 2016
Actual Study Completion Date : July 15, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Ranibizumab

Arm Intervention/treatment
Experimental: Ranibizumab
Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection
Drug: Ranibizumab
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.
Other Name: RFB002




Primary Outcome Measures :
  1. Number of Patients Treated and Re-treated Based on Presence/Absence of Active Leakage [ Time Frame: Screening, Month 2, Month 6 ]
    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

  2. Number of Patients Treated and Re-treated Based on Presence/Absence of Macular Edema [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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

  3. Number of Patients Treated and Re-treated Based on Presence/Absence of Cysts [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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

  4. Number of Patients Treated and Re-treated Based on Presence/Absence of Intra-retinal Fluid [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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

  5. Change in Central Subfield Thickness (CSFT) [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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.

  6. Change in Central Subfield Volume (CSV) [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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.

  7. Number of Patients Treated and Re-treated Based on Presence/Absence of Sub-retinal Fluid [ Time Frame: Screening, Month 2, Month 6, Month 12 ]
    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

  8. Number of Patients Treated and Re-treated Based on Presence/Absence of Clinically Significant Abnormalities [ Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12 ]
    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.

  9. Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 5 Letters [ Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12 ]
    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.

  10. Number of Patients Treated and Re-treated Based on Improvement in Best Corrective Visual Acuity (BCVA) < 10 Letters [ Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12 ]
    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.

  11. Number of Patients in Different Categories of Changes From Baseline in BCVA [ Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12 ]
    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.


Secondary Outcome Measures :
  1. Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 6 and Month 12 on Study Eye [ Time Frame: Baseline, Month 6, Month 12 ]
    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.

  2. Mean Number of Ranibizumab Injection [ Time Frame: Baseline to Month 12 ]
    Mean number of ranibizumab injection is reported as number of injections per patient.

  3. Time to Re-treatment [ Time Frame: Baseline to Month 12 ]
    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.

  4. Number of Patients Having Ocular and/or Systemic Adverse Event (AE) [ Time Frame: Baseline to Month 12 ]
    Number of patients with any systemic AE, with serious systemic AE, with an ocular AE, with an ocular serious AE are reported

  5. Change in Patient Quality of Life From Baseline to Month 2 and Month 12 [ Time Frame: Baseline, Month 2, 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02034006


Locations
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Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Bari, BA, Italy, 70124
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Desenzano del Garda, BS, Italy, 25015
Novartis Investigative Site
Bolzano, BZ, Italy, 39100
Novartis Investigative Site
Cagliari, CA, Italy, 09124
Novartis Investigative Site
Catania, CT, Italy, 95123
Novartis Investigative Site
Catanzaro, CZ, Italy, 88100
Novartis Investigative Site
Firenze, FI, Italy, 50134
Novartis Investigative Site
Rapallo, GE, Italy, 16035
Novartis Investigative Site
Terracina, LT, Italy, 04019
Novartis Investigative Site
Milano, MI, Italy, 20100
Novartis Investigative Site
Milano, MI, Italy, 20122
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Palermo, PA, Italy, 90127
Novartis Investigative Site
Padova, PD, Italy, 35100
Novartis Investigative Site
Padova, PD, Italy, 35128
Novartis Investigative Site
Perugia, PG, Italy, 06100
Novartis Investigative Site
Pisa, PI, Italy, 56124
Novartis Investigative Site
Parma, PR, Italy, 43100
Novartis Investigative Site
Roma, RM, Italy, 00133
Novartis Investigative Site
Roma, RM, Italy, 00161
Novartis Investigative Site
Roma, RM, Italy, 00198
Novartis Investigative Site
Siena, SI, Italy, 53100
Novartis Investigative Site
Torino, TO, Italy, 10122
Novartis Investigative Site
Conegliano, TV, Italy, 31015
Novartis Investigative Site
Udine, UD, Italy, 33100
Novartis Investigative Site
Varese, VA, Italy, 21100
Novartis Investigative Site
Negrar, VR, Italy, 37024
Novartis Investigative Site
Napoli, Italy, 80131
Novartis Investigative Site
Napoli, Italy, 80138
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02034006    
Other Study ID Numbers: CRFB002FIT01
2013-003334-33 ( EudraCT Number )
First Posted: January 13, 2014    Key Record Dates
Results First Posted: February 18, 2019
Last Update Posted: February 18, 2019
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
pathological myopia
choroidal neovascularization
ranibizumab
mono-bilateral
poor visual acuity
retinal disease
eye disease
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Additional relevant MeSH terms:
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Neoplasm Metastasis
Vision Disorders
Vision, Low
Myopia
Choroidal Neovascularization
Neovascularization, Pathologic
Neoplastic Processes
Neoplasms
Pathologic Processes
Refractive Errors
Eye Diseases
Metaplasia
Choroid Diseases
Uveal Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents