Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD (TREND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01948830
Recruitment Status : Completed
First Posted : September 24, 2013
Results First Posted : December 15, 2016
Last Update Posted : April 17, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study was designed to evaluate the efficacy and safety of two different regimens of 0.5 mg ranibizumab given as intravitreal injection in patients with neovascular age-related macular degeneration

Condition or disease Intervention/treatment Phase
Age-related Macular Degeneration Choroidal Neovascularization Drug: Ranibizumab 0.5mg Phase 3

Detailed Description:

This was a 12-month, phase IIIb, randomized, Visual Acuity assessor-masked, multi-center, interventional study assessing the efficacy and safety of the TER vs monthly regimens of 0.5 mg ranibizumab intravitreal (IVT) injections in patients with newly diagnosed nAMD. Patients will be randomized 1:1 into one of two treatment arms, Treat and Extend or monthly regimens.

There will be 3 periods in this study: Screening period (up to 14days), treatment period (11 months), follow-up period (1 month). At randomization visit patients will be randomized into one of the 2 treatment groups Group I ranibizumab 0.5 mg based on monthly treatment or Group II ranibizumab 0.5 mg based on TER (randomization ratio of 1:1) and will receive the first dose of Investigational treatment. Patients in Group I the following visits will perform on monthly intervals. For patients in Group II the investigator will evaluate disease activity (i.e., signs of exudation) based on SD-OCT, and in case of absence of disease activity every next visit will be 2 weeks), with a maximum of a 12-week interval.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 650 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A 12-month, Phase 3b, Randomized, Visual Acuity Assessor-masked, Multicenter Study Assessing the Efficacy and Safety of Ranibizumab 0.5mg in Treat and Extend Regimen Compared to Monthly Regimen, in Patients With Neovascular Age-related Macular Degeneration
Actual Study Start Date : December 17, 2013
Actual Primary Completion Date : November 19, 2015
Actual Study Completion Date : November 19, 2015


Arm Intervention/treatment
Active Comparator: Group I ranibizumab 0.5 mg monthly
Ranibizumab 0.5 mg/0.05 mL (Monthly regimen) up to month 11
Drug: Ranibizumab 0.5mg
0.5 mg ranibizumab (intravitreal injections) prefilled syringe)
Other Name: Lucentis

Active Comparator: Group II ranibizumab 0.5 mg TER
Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen up to month 11
Drug: Ranibizumab 0.5mg
0.5 mg ranibizumab (intravitreal injections) prefilled syringe)
Other Name: Lucentis




Primary Outcome Measures :
  1. Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 [ Time Frame: Baseline to month 12 ]
    Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement


Secondary Outcome Measures :
  1. Number of Visits Scheduled [ Time Frame: From Month1 to Month 11 ]
    The number of visits scheduled according to the treat and extend regimen after treatment initiation

  2. Change in BCVA From Baseline to Month 12 [ Time Frame: Baseline to Month 12 ]
    Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters

  3. Average BCVA Change From Baseline to Month 12 [ Time Frame: Baseline and every month for 12 months ]

    Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters.

    Mean Visual Acuity was averaged over all monthly assessments from Baseline to Month 12


  4. Mean Change in Visual Acuity BCVA (Letters) From Baseline to Month 12 [ Time Frame: Baseline and every month for 12 months ]
    Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like charts while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and compare to Baseline

  5. Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 [ Time Frame: Baseline and every month for 12 months ]
    BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 12 as compared with baseline

  6. Number of Patients With Best Corrected Visual Acuity (BCVA) Loss <5, <10, and <15 Letters by Visit [ Time Frame: Baseline and every month for 12 months ]
    Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters.Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters.

  7. Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 [ Time Frame: Baseline and every month for 12 months ]
    Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 12 indicates a positive outcome

  8. The Mean Number of Treatment Frequency [ Time Frame: Month 12 ]
    The number of injections received

  9. The Average Number of Days Between Injections [ Time Frame: Month 12 ]
    The average dosing interval was measured as the average number of days between injections

  10. Percentage of Participants With Fluid Free Macula Over Time up to Month 12 [ Time Frame: Month 12 ]
    OCT (optical coherence tomography) was used to assess intra-retinal fluid as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography). Fluid free macula refers to absence of macular edema (as assessed by the reading center). The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the macular edema (center involvement) at study completion. These total counts are used as the denominator for the percentages

  11. Change in Central Subfield Retinal Thickness (CSFT) Over Time [ Time Frame: Month 12 ]
    OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center. The Ns in the rows is the number of patients with a value for both baseline and the specific post-baseline visit

  12. Percentage of Patients With Choroidal Neovascularization (CNV) Leakage Assessed by Fluorescein Angiography (FA) in the Study Eye at [ Time Frame: Month 12 ]
    To evaluate presence of active CNV leakage on fluorescein angiography (FA) by reading center over time up to Month 12. The full analysis set was used for this evaluation but the count presented are the counts of patients in the specific treatment group who have a value for the presence of leakage at study completion. These total counts are used as the denominator for the percentages.

  13. Change From Baseline in Composite Score of the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25) [ Time Frame: Baseline, Month 12 ]
    The survey consisted 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. The score of each individual question ranged from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also ranged from 0 to 100 as they are calculated as total scores divided by the number of questions. The higher the values of total scores represent better outcome



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female patients, ≥50 years of age with signed informed consent before study procedures
  • Visual impairment predominantly due to nAMD.
  • Active CNV secondary to AMD confirmed by presence of active leakage from CNV seen by fluorescein angiography (FA) and/or color fundus photography
  • Presence of intra- or subretinal fluid/hemorrhage seen by SD-OCT
  • BCVA score must be ≤ 78 and ≥ 23 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximate Snellen equivalent of 20/32 and 20/320)

Key Exclusion Criteria:

  • Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
  • Stroke or myocardial infarction within 3 months prior to Screening.
  • Any active periocular or ocular infection or inflammation in both eyes.
  • Ocular disorders in the study eye at the time of enrollment that may confound interpretation of study results and compromise visual acuity.
  • Presence of amblyopia or amaurosis in the fellow eye.
  • History of treatment with any anti-angiogenic drugs (including any anti- vascular endothelial growth factor (anti-VEGF) agents) e.g., bevacizumab [Avastin®], aflibercept [Eylea®]) or vPDT in the study eye.
  • History of intravitreal treatment with corticosteroids within 6 months and history of intra-ocular surgery within 3 months in the study eye prior to the Screening.
  • Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01948830


  Show 91 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01948830     History of Changes
Other Study ID Numbers: CRFB002A2411
2013-002626-23 ( EudraCT Number )
First Posted: September 24, 2013    Key Record Dates
Results First Posted: December 15, 2016
Last Update Posted: April 17, 2017
Last Verified: March 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ranibizumab, Lucentis, choroidal neovascularization, age-related macular degeneration, treat and extend regimen

Additional relevant MeSH terms:
Layout table for MeSH terms
Macular Degeneration
Neovascularization, Pathologic
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Metaplasia
Pathologic Processes
Choroid Diseases
Uveal Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents