Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion - Full Text View

Purpose

The present study will provide additional efficacy and safety data for 0.5-mg ranibizumab using as needed (PRN) dosing over 24 months in patients with visual impairment due to macular edema secondary to Central Retinal Vein Occlusion (CRVO). Spectral domain high-definition optical coherence tomography (OCT) images will be analyzed to gain insights into predictive factors for disease progression and the possibility of reduced monitoring will be assessed in Year 2. The results of this open-label study will provide long-term safety and efficacy data to further guide recommendations on the use of ranibizumab in this indication.

Condition	Intervention	Phase
Macular Edema Central Retinal Vein Occlusion	Drug: Ranibizumab 0.5 mg/0.05 ml, intravitreal injection	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 24-month, Phase IIIb, Open-label, Single Arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Edema Methamphetamine

Drug Information available for: Ranibizumab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Mean change in BCVA at month 12 compared to baseline for evaluating the efficacy of an individualized stabilization criteria driven PRN dosing regimen [ Time Frame: From baseline to month 12 ] [ Designated as safety issue: No ]
For the mean change of BCVA at Month 12 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test will be calculated

Secondary Outcome Measures:

Mean change in BCVA from Month 1 through Month 24 compared to Baseline [ Time Frame: From baseline and followed up Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Mean change in BCVA from Month the time point of the first treatment interruption (due to BCVA stabilization) through Month 24 by visit [ Time Frame: First treatment interruption through month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Mean average change in BCVA from Month 1 through Month 12 and from Month 1 through Month 24 compared to Baseline [ Time Frame: From Month 1 and followed up month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Mean average change in BCVA from the time point of the first treatment interruption (due to BCVA stabilization) through Month 12 and/or Month 24 [ Time Frame: From Month 1 and followed up Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Number and proportion of patients with a BCVA value of ≥ 73 letters (approximate 20/40 Snellen chart equivalent) at Month 12 and Month 24 [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Number and proportion of patients with a BCVA value of < 15 letters from Baseline up to Month 12 and Month 24 [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Mean change in CRC-assessed CSFT from Month 1 through Month 12 and Month 24 compared to Baseline [ Time Frame: Baseline through Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.
Mean change in patient-reported outcomes in NEI-VFQ-25 score (compared score and subscales) at Month 12 and Month 24 compared to Baseline [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
The survey consists of 25 items representing 11 vision-related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. Scores per visit and of the change from Baseline for the composite score and subscales will be summarized descriptively by visit.
The number and proportion of patients with a BCVA improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters from Baseline to Month 12 and Month 24 in the study eye, by visit [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test

Estimated Enrollment:	350
Study Start Date:	February 2012
Estimated Study Completion Date:	April 2015
Estimated Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ranibizumab arm Open-label single arm. The investigational drug in this study is 0.5 mg ranibizumab. All patients will be assigned and will receive the same treatment.	Drug: Ranibizumab 0.5 mg/0.05 ml, intravitreal injection Patients will receive the first dose at Baseline, as an intravitreal injection with a standard dose of 0.5 mg/0.05 ml. Patients will receive at least 3 study treatments at monthly intervals (Day 1, Month 1 and Month 2). The last mandatory dose during treatment initiation will be administered approximately 60 days after the first study treatment. If there is no improvement in VA over the course of the first 3 injections, continued treatment is not recommended and the patient may receive alternative treatment at the investigator's discretion.

Arms

Assigned Interventions

Experimental: Ranibizumab arm

Open-label single arm. The investigational drug in this study is 0.5 mg ranibizumab. All patients will be assigned and will receive the same treatment.

Drug: Ranibizumab 0.5 mg/0.05 ml, intravitreal injection

Patients will receive the first dose at Baseline, as an intravitreal injection with a standard dose of 0.5 mg/0.05 ml. Patients will receive at least 3 study treatments at monthly intervals (Day 1, Month 1 and Month 2). The last mandatory dose during treatment initiation will be administered approximately 60 days after the first study treatment. If there is no improvement in VA over the course of the first 3 injections, continued treatment is not recommended and the patient may receive alternative treatment at the investigator's discretion.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients ≥ 18 years of age
Diagnosis of visual impairment exclusively due to ME secondary to CRVO
BCVA score at Screening and Baseline between 73 and 19 letters Early Treatment Diabetic Retinopathy Study (ETDRS), inclusively (approximate Snellen chart equivalent of 20/40 and 20/400)

Exclusion Criteria:

Uncontrolled blood pressure defined as systolic value of > 160 mm Hg or diastolic value of > 100 mm Hg at Screening or Baseline.
Any active periocular or ocular infection or inflammation at Screening or Baseline in either eye
Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before Baseline in either eye
Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline (eg, sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®])

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535261

Contacts

Contact: Novartis Pharmaceuticals	+41613241111
Contact: Novartis Pharmaceuticals

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01535261 History of Changes
Other Study ID Numbers:	CRFB002E2401, 2011-002350-31
Study First Received:	February 14, 2012
Last Updated:	May 9, 2013
Health Authority:	United States: Food and Drug Administration Austria: Agency for Health and Food Safety Australia: Department of Health and Ageing Therapeutic Goods Administration Canada: Health Canada Czech Republic: State Institute for Drug Control Denmark: National Board of Health France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Greece: National Organization of Medicines Hungary: National Institute of Pharmacy Ireland: Irish Medicines Board Italy: The Italian Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Slovakia: State Institute for Drug Control Spain: Agencia Española de Medicamentos y Productos Sanitarios Switzerland: Swissmedic Sweden: The National Board of Health and Welfare Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Ophthalmology
Ranibizumab
Central Retinal Vein Occlusion

Additional relevant MeSH terms:

Vision, Low
Edema
Macular Edema
Retinal Vein Occlusion
Vision Disorders
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases

Eye Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases

ClinicalTrials.gov processed this record on May 22, 2013

Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (CRYSTAL)