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.

NCT02034006 | Completed Phase 3 Results

• 2 other identifiers: CRFB002FIT012013-003334-33
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 31

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.

Conditions

Choroidal Neovascularization Secondary to Pathologic Myopia

Keywords

pathological myopia; choroidal neovascularization; ranibizumab; mono-bilateral; poor visual acuity; retinal disease; eye disease; Angiogenesis Inhibitors; Angiogenesis Modulating Agents

Outcome Measures

Primary Outcomes (11)

• 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

  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

  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

  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

  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.

  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.

  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

  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.

  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.

  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.

  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.

  Baseline, Month 1, Month 2, Month 3, Month 6, Month 12

Secondary Outcomes (5)

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

  Baseline, Month 6, Month 12

• Mean Number of Ranibizumab Injection

  Baseline to Month 12

• Time to Re-treatment

  Baseline to Month 12

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

  Baseline to Month 12

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

  Baseline, Month 2, Month 12

Study Arms (1)

Ranibizumab

EXPERIMENTAL

Patients treated with a single ranibizumab 0.5 mg/0.05ml intravitreal injection

Drug: Ranibizumab

Interventions

Ranibizumab DRUG

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.

Also known as: RFB002

Ranibizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Bari, BA, 70124, Italy

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Desenzano del Garda, BS, 25015, Italy

Location

Novartis Investigative Site

Bolzano, BZ, 39100, Italy

Location

Novartis Investigative Site

Cagliari, CA, 09124, Italy

Location

Novartis Investigative Site

Catania, CT, 95123, Italy

Location

Novartis Investigative Site

Catanzaro, CZ, 88100, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Rapallo, GE, 16035, Italy

Location

Novartis Investigative Site

Terracina, LT, 04019, Italy

Location

Novartis Investigative Site

Milan, MI, 20100, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Padua, PD, 35100, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Perugia, PG, 06100, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Parma, PR, 43100, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Roma, RM, 00198, Italy

Location

Novartis Investigative Site

Siena, SI, 53100, Italy

Location

Novartis Investigative Site

Torino, TO, 10122, Italy

Location

Novartis Investigative Site

Conegliano, TV, 31015, Italy

Location

Novartis Investigative Site

Udine, UD, 33100, Italy

Location

Novartis Investigative Site

Varese, VA, 21100, Italy

Location

Novartis Investigative Site

Negrar, VR, 37024, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Napoli, 80138, Italy

Location

Related Publications (1)

• 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.

  PMID: 30680452 DERIVED

MeSH Terms

Conditions

Myopia, Degenerative; Choroidal Neovascularization; Retinal Diseases; Eye Diseases

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Myopia; Refractive Errors; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 13, 2014
• Study Start: June 10, 2014
• Primary Completion: July 15, 2016
• Study Completion: July 15, 2016
• Last Updated: February 18, 2019
• Results First Posted: February 18, 2019

Record last verified: 2018-10

Locations

IT (31)