LUCAS (Lucentis Compared to Avastin Study)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Oslo University Hospital ( Ullevaal University Hospital )
ClinicalTrials.gov Identifier:
NCT01127360
First received: May 19, 2010
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

Age-related macular degeneration (AMD) is the most common cause of blindness in individuals over 50 years of age. Bevacizumab and ranibizumab are two agents developed by the American pharmaceutical corporation Genentech, both of which inhibit blood vessel growth factors. These drugs, when injected intraocularly, reduce the pathological growth of blood vessels under the macula (the central area of the retina which is responsible for detailed vision). Bevacizumab (Avastin) is an antibody developed for intravenous treatment of metastasized colon cancer. Ranibizumab (Lucentis) is an antibody fragment developed from a similar antibody. It was introduced 2006 as an effective treatment for wet AMD. Treatment of wet AMD with Avastin has experimentally shown similar effects to ranibizumab, and has been used off-label in many countries, both before and after Lucentis received approval. Ranibizumab has, in controlled studies, been shown to be effective in improving vision in some patients, and to stop further visual loss in most patients. Treatment costs are, however, up to 50 times higher compared to use of bevacizumab, where a single vial can be used to prepare as many as 20 injections. Although the effects of Avastin have not been documented in large controlled studies, there are hundreds of articles published with regard to its effect and safety. Avastin has no formal approval for the indication AMD, but is used in many countries because of its effectiveness and low price. Such use has been criticized on the grounds of insufficient documentation. There is thus a recognized need for large randomized studies to garner proper scientific proof of Avastin's effectiveness regarding wet AMD.

This protocol describes such a randomized multicenter study, performed in Norway, comparing ranibizumab and bevacizumab use for AMD. The goal of the study is to demonstrate if the two agents are equivalent regarding both efficacy and safety. A total of 420 patients with objective evidence of wet AMD will be randomized to a double-blind treatment with ranibizumab or bevacizumab over the course of 2 years. The treatment interval will be determined by protocol called "inject and extend." The shortest interval will be 4 weeks and the longest 12 weeks. The goal of such a protocol is to determine an appropriate individual treatment regimen by gradually increasing the interval between injections. An extended interval between each examination and injection visit can reduce the burden upon an ophthalmology department, as well as increasing a patient's comfort. Such a protocol could also aid in reducing the risk of recurrence.


Condition Intervention Phase
Wet Age-related Macular Degeneration
Drug: Bevacizumab (Avastin)
Drug: Ranibizumab (Lucentis)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Lucentis Compared to Avastin Study. A Randomized, Double Blind, Prospective Multicenter Study Comparing the Effect of Intravitreal Injection of Bevacizumab (Avastin)to Ranibizumab (Lucentis)When Given to Patients With Exudative (Wet) Age-related Macular Degeneration

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Mean change in VA at 1 and 2 years as measured with the ETDRS chart [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]
    Mean change in VA at 1 and 2 years as measured with the ETDRS chart (with a non-inferiority limit of 5 letters)


Secondary Outcome Measures:
  • Number of treatments. [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]
    Number of treatments.

  • Proportion of patients losing fewer than 15 letters on ETDRS chart [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]
    Proportion of patients losing fewer than 15 letters on ETDRS chart

  • Macular morphology as measured by FA and OCT after 2 years. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]
    Macular morphology as measured by FA and OCT after 2 years.

  • Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Frequency of ophthalmological and other health related adverse events during the 2 year study.

  • Number of non-responders. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]
    Number of non-responders.


Enrollment: 420
Study Start Date: March 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bevacizumab Drug: Bevacizumab (Avastin)
Intravitreal injection
Active Comparator: Ranibizumab Drug: Ranibizumab (Lucentis)
Intravitreal injection

Detailed Description:

LUCAS (LUcentis Compared to Avastin Study) A randomized, double-blind, prospective multicenter study comparing the effect of intravitreal injection of bevacizumab (Avastin) to ranibizumab (Lucentis) when given to patients with exudative (wet) age-related macular degeneration in Norway.

Version: 4, Protocol: 166-09, EudraCT: 2008-004225-41

Purpose:

LUCAS is a prospective, randomized, multicenter study comparing the effects of intravitreal injection of bevacizumab (Avastin) with ranibizumab (Lucentis) when given to patients with exudative (wet) AMD in Norway.

The study will include 420 patients to be recruited starting March 2009. The study will continue for 2 years after completed enrollment.

Design:

LUCAS is a multicenter, randomized, double-blind study, with 1:1 parallel groups treated with either bevacizumab (Avastin) 0.05 ml (25 mg/ml) or ranibizumab (Lucentis) 0,05 ml (10 mg/ml). The drug is injected intravitreally according to an "inject and extend" principle (5).

Randomization will be stratified by center and performed with minimization according to prognostic factors.

Treatment Regimen:

Bevacizumab (Avastin) will be given as an intravitreal injection of 0.05ml (25 mg/ml) from a vial containing 4 ml.

Ranibizumab (Lucentis) will be given as an intravitreal injection of 0.05 ml (10 mg/ml) from a vial containing 0.23 ml.

Follow-up and treatment will follow a principle called "inject and extend." This connotes the following: initial follow-up and injection with a 4 week intervals until the macula is dry. When dry, then follow-up and injection will be increased 2 weeks at a time. If the patient has a recurrence of wet AMD, then the interval is reduced by 2 weeks at a time until the macula is once again dry. The shortest interval is 4 weeks. When once again extending, the treatment interval shall not be as long as the interval of the original recurrence, as this could confer risk for new activity. Therefore further follow-up and injection occurs at the "ideal" interval which is hereby defined as being 2 weeks less than that of the original recurrence. With this method, the patient receives an injection at each follow-up, presuming that no complications occur. The maximum interval is limited to 12 weeks. Treatment will continue for 2 years. After the study is completed, then the patient is to be offered continued treatment, in accordance with the ophthalmology department's routines, If there is no response to treatment after 3 injections with a 4 week interval, then the patient shall be removed from the study and be offered alternative treatment, such as combination treatment with photodynamic therapy (PDT).

  Eligibility

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

Inclusion Criteria:

  1. Men and women.
  2. Age ≥50 years.
  3. Wet AMD in the study eye, defined as:

    Not previously treated active choroidal neovascular membrane (CNV), including retinal angiomatous proliferation (RAP), with edema involving the fovea as demonstrated with optical coherence tomography (OCT) and fluorescein angiography (FA). FA shall not be older than 7 days at randomization.

    Best corrected visual acuity (BCVA) in the study eye 20/25 - 20/320.

  4. Only one eye of each study patient may be recruited into the study. If the non-study eye is being treated with intravitreal anti-VEGF therapy, or develops wet AMD, then the same drug being used in the study eye shall be used in the non-study eye. Treatment must be given double-blind in the non-study eye as well.

Exclusion Criteria:

  1. Previous treatment of CNV in the study eye.
  2. Participation in another AMD study, or use of other investigational medicines.
  3. Anti-VEGF treatment in the non-study eye during the last 4 weeks.
  4. Earlier or current treatment with systemic anti-VEGF drug.
  5. Subretinal hemorrhage and/or fibrosis that involves ≥50 percent of the CNV lesion in the study eye.
  6. CNV of other pathogenesis, such as pathologic myopia (defined as having a spherical equivalent of >8 diopters myopia) or Presumed Ocular Histoplasmosis Syndrome (POHS).
  7. Presence of retinal diseases other than AMD (diabetic retinopathy, macular hole, etc) that lead to loss of visual acuity in the study eye.
  8. Cataract that will presumably require operation within 2 years or other intraocular surgery or laser treatment during the last 3 months.
  9. Impaired visualization of the retina (by vitreous hemorrhage, corneal dystrophy, etc.) that may hamper adequate diagnosis.
  10. Intraocular pressure ≥25 mm Hg, measured before mydriasis, or uncontrolled glaucoma as evaluated by the examining ophthalmologist.
  11. Active uveitis in the study eye or intraocular inflammation after use of Lucentis or Avastin in the non-study eye.
  12. Infection in one or both eyes.
  13. Premenopausal women who do not use appropriate birth control, or who are nursing.
  14. Patients who for mental or physical reasons are unable to comply with the study's procedures,
  15. Serious disease where there is a probability of death within the duration 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: NCT01127360

Locations
Norway
Department of Ophthalmology, Oslo University Hospital
Oslo, Norway, 0407
Sponsors and Collaborators
Ullevaal University Hospital
Investigators
Study Director: Andreas Moan Director of Research at Oslo University Hospital
Study Chair: Ragnheidur Bragadottir, MD. PhD. Department of Ophthtalmology, Oslo University Hospital
Principal Investigator: Karina Berg, MD. Department of Ophthalmology, Oslo University Hospital
Study Chair: Terje Pedersen, Professor Department of Preventative Medicine, Oslo University Hospital
  More Information

No publications provided

Responsible Party: Oslo University Hospital ( Ullevaal University Hospital )
ClinicalTrials.gov Identifier: NCT01127360     History of Changes
Other Study ID Numbers: 1008
Study First Received: May 19, 2010
Last Updated: October 25, 2012
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Oslo University Hospital:
Anti-VEGF
Ranibizumab
Bevacizumab
wet AMD
macular degeneration

Additional relevant MeSH terms:
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014