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)

• 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: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ricci F, Staurenghi G, Varano M, Eandi C, Sinibaldi TL, Colombo L, Bartezaghi M, Bassanini S. OLIMPIC: a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):759-768. doi: 10.1007/s00417-019-04248-8. Epub 2019 Jan 24.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02034006
• Other Study ID Numbers: CRFB002FIT01; 2013-003334-33 ( EudraCT Number )
• First Posted: January 13, 2014
• Results First Posted: February 18, 2019
• Last Update Posted: February 18, 2019
• Last Verified: October 2018

• 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:

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