Comparison of Ranibizumab Monotherapy and Ranibizumab Combination Therapies in Recurrent or Persistent Choroidal Neovascularization Secondary to Age-related Macular Degeneration

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Stefan Sacu, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01162746
First received: July 14, 2010
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

Age-related macular degeneration (AMD) is by far the most common disorder in the group of irreversible causes of visual disability. AMD leads to dysfunction and loss of photoreceptors in the central retina. Neovascular AMD (nAMD) affects visual function early in the disease process and severely compromises the highly developed functions of the macula, such as perception of details, central fixation, color vision, and reading ability. AMD-related visual impairment is associated with a loss of autonomy and quality of life. Current therapeutic approaches target vascular endothelial growth factor (VEGF), which has been identified as a main cytokine in the pathogenesis of nAMD. Ranibizumab, the fab-fragment of an antibody targeting VEGF is approved for the treatment of nAMD applied intravitreally in monthly intervals until the disease activity is stopped. However, a significant proportion of patients with nAMD suffer from persistent or recurring disease with the need of continuous anti-VEGF therapy over months and years, often leading to irreversible changes in the photoreceptor layer and the pigment epithelium.

Recent studies regarding the treatment of nAMD utilized different forms of therapies, combining photodynamic therapy with verteporfin (PDT) and ranibizumab, as well as therapeutic regimen containing steroids. Even though these studies did not provide evidence that combination therapies are superior to ranibizumab monotherapy, studies were only conducted with patients with previously untreated nAMD. Therefore, currently there is no alternative therapeutic approach for patients with recurrent or persistent form of nAMD after multiple treatments with ranibizumab monotherapy.

The purpose of this study is to assess the treatment effect of reduced fluence PDT and intravitreal ranibizumab versus intravitreal dexamethasone and ranibizumab versus intravitreal ranibizumab monotherapy in patients with persistent or recurrent choroidal neovascularization (CNV) due to AMD.

The investigators hypothesis is that these findings will offer new insights in the management of persistent or recurrent CNV secondary to AMD.


Condition Intervention Phase
Age-Related Macular Degeneration
Neovascularization, Choroidal
Drug: Intravitreal dexamethasone and intravitreal ranibizumab
Drug: Intravitreal ranibizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Intravitreal Dexamethasone With Intravitreal Ranibizumab Versus Intravitreal Ranibizumab Monotherapy in Recurrent or Persistent Choroidal Neovascularization Secondary to Age-related Macular Degeneration A Prospective, Randomized, Clinical Study

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • • Central visual function. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • • Changes of intraretinal morphologies (central retinal thickness). [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • • Measurement of levels of proteins in the ocular fluid. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • • Perfusion of the neovascular net (FLA and ICG). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • • Chorioretinal perfusion (ICG). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • • Retinal sensitivity (mfERG, Nidek MP-1 microperimetry) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intravitreal dexamethasone and intravitreal ranibizumab

Patients will receive intravitreal dexamethasone using a special drug delivery system and same day intravitreal ranibizumab.

Study medications are initially given at the baseline visit. At each subsequent monthly follow-up visit, ranibizumab is administered if further visual deterioration or persistence of sub-/intraretinal fluid is detected in the examination. At month 3, 6, 9 and 12 further treatments with intravitreal dexamethasone in combination with intravitreal ranibizumab are given if leakage is detected in fluorescein or indocyanine green (FLA or ICG) angiography, in case of further vision decrease or persistence of sub-/intraretinal fluid in OCT.

Drug: Intravitreal dexamethasone and intravitreal ranibizumab

Patients will receive intravitreal dexamethasone using a special drug delivery system and same day intravitreal ranibizumab.

Study medications are initially given at the baseline visit. At each subsequent monthly follow-up visit, ranibizumab is administered if further visual decrease or persistence of sub-/intraretinal fluid is detected in the examination. At month 3, 6, 9 and 12 further treatments with intravitreal dexamethasone in combination with intravitreal ranibizumab are given if leakage is detected in fluorescein or indocyanine green (FLA or ICG) angiography, in case of further vision decrease or persistence of sub-/intraretinal fluid in OCT.

Active Comparator: Intravitreal ranibizumab
Patients will receive intravitreal ranibizumab monotherapy (cohort 3). Study medications are initially given at the baseline visit. At each subsequent monthly follow-up visit, ranibizumab is administered if further visual deterioration or persistence of sub-/intraretinal fluid is detected in the examination
Drug: Intravitreal ranibizumab
Patients will receive intravitreal ranibizumab monotherapy (cohort 3). Study medications are initially given at the baseline visit. At each subsequent monthly follow-up visit, ranibizumab is administered if further visual deterioration or persistence of sub-/intraretinal fluid is detected in the examination

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 50 years of age or older.
  • Patients with persistent or recurrence subfoveal CNV lesion secondary to AMD
  • Patients who have a BCVA score better than 20/400 in the study eye using ETDRS.
  • At least 6 initial intravitreal ranibizumab monotherapy
  • The initial intravitreal ranibizumab treatment performed within the last 6 - 12 months.

Exclusion Criteria:

  • Any prior initial intravitreal treatment other than intravitreal ranibizumab.
  • History of glaucoma filtration surgery, corneal transplant surgery or extracapsular extraction of cataract with phacoemulsification within six months preceding Visit 1, or a history of post-operative complications within the last 12 months preceding Visit 1 in the study eye (uveitis, cyclitis etc.).
  • History of uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma mediation).
  • Aphakia or absence of the posterior capsule in the study eye.
  • Presence of a retinal pigment epithelial tear involving the macula in the study eye.
  • Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either require medical or surgical intervention during the three-month study period to prevent or treat visual loss that might result from that condition.
  • Active intraocular inflammation (grade trace or above) in the study eye.
  • Any active infection involving eyeball adnexa.
  • Vitreous hemorrhage or history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye.
  • Other ocular conditions that require chronic concomitant therapy with systemic or topical ocular corticosteroids. Chronic concomitant therapy is defined as multiple doses taken daily for three or more consecutive days at any time within six months prior to screening or during the course of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01162746

Contacts
Contact: Stefan Sacu, MD +43140400 ext 7962 stefan.sacu@meduniwien.ac.at

Locations
Austria
Department of Ophthalmology, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Principal Investigator: Stefan Sacu, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Stefan Sacu, MD Department of Ophthalmology, Medical University of Vienna
  More Information

No publications provided

Responsible Party: Stefan Sacu, Ass.-Prof. Priv.-Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01162746     History of Changes
Other Study ID Numbers: 10032011
Study First Received: July 14, 2010
Last Updated: January 2, 2014
Health Authority: Austria: Ethics Committee of the Medical University of Vienna, Austria
Austria: Agency for Health and Food Safety
Austria: Federal Office for Safety in Health Care

Additional relevant MeSH terms:
Macular Degeneration
Neovascularization, Pathologic
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Metaplasia
Pathologic Processes
Choroid Diseases
Uveal Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014