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An Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization Secondary to AMD or Macular Edema Secondary to RVO

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00379795
First received: September 21, 2006
Last updated: January 30, 2013
Last verified: January 2013
History of Changes
Results First Received: April 1, 2011  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Choroidal Neovascularization, Age-related Macular Degeneration
Intervention: Drug: Ranibizumab 0.5 mg

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This is an open label multicenter extension study for participants who have completed one of the following studies: FVF2428g (NCT00056823), FVF2587g (NCT00061594) or FVF2598g (NCT0056823). Cohort 1 includes patients with Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were classified according to ranibizumab exposure in the previous study and in the extension study. 63 participants (Untreated Group) did not receive study drug in this extension study or in the previous studies and are not included in the safety analyses.

Reporting Groups
  Description
RanibizumabTreated Initial Mono In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Participants in this group received ranibizumab monotherapy (Mono) in previous studies, that is, ranibizumab alone in study FVF2598g or ranibizumab in combination with sham photodynamic therapy (PDT) in study FVF2587g.
RanibizumabTreated Initial + PDT In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. This group includes participants who received ranibizumab in combination with photodynamic therapy in Study FVF2428g
RanibizumabTreated Sham XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated Sham Crossover (XO) includes participants who received sham intravitreal injections before crossing over to receive ranibizumab intravitreal injections in study FVF2598g or this extension study.
Ranibizumab Treated PDT XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated PDT XO includes participants who received sham intravitreal injections in combination with photodynamic therapy in study FVF2428g or study FVF2587g before crossing over to receive ranibizumab intravitreal injections in study FVF2428g, study FVF2587g or this study.
Ranibizumab Untreated Group In this extension study participants did not receive Ranibizumab. Participants in this group were enrolled in one of the following studies: FVF2428g (NCT00056823), FVF2587g (NCT00061594) FVF2598g (NCT0056823) but did not receive Ranibizumab intravitreal injections in that study or in this extension study (FVF3426g).

Participant Flow:   Overall Study
    RanibizumabTreated Initial Mono     RanibizumabTreated Initial + PDT     RanibizumabTreated Sham XO     Ranibizumab Treated PDT XO     Ranibizumab Untreated Group  
STARTED     526     74     116     74     63  
Received Ranibizumab in Extension Study     377     41     113     55     0  
COMPLETED     50     23     23     6     14  
NOT COMPLETED     476     51     93     68     49  
Death                 31                 8                 6                 4                 7  
Adverse Event                 17                 3                 3                 1                 4  
Lost to Follow-up                 8                 1                 2                 1                 4  
Physician Decision                 25                 0                 2                 2                 2  
Withdrawal by Subject                 94                 11                 19                 7                 14  
Subject non-compliance                 7                 2                 0                 0                 1  
Verteporfin photodynamic therapy in eye                 3                 0                 0                 1                 0  
Subjects condition mandated intervention                 34                 9                 7                 5                 7  
Sponsor's decision                 257                 17                 54                 47                 10  



  Baseline Characteristics
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Reporting Groups
  Description
RanibizumabTreated Initial Mono In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Participants in this group received ranibizumab 0.5 mg monotherapy, that is, ranibizumab alone in study FVF2598g or ranibizumab in combination with sham photodynamic therapy (PDT) in study FVF2587g.
RanibizumabTreated Initial + PDT In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. This group includes participants who received ranibizumab 0.5 mg intravitreal injections in combination with photodynamic therapy in Study FVF2428g.
RanibizumabTreated Sham XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated Sham Crossover (XO) includes participants who received sham intravitreal injections before crossing over to receive ranibizumab 0.5mg intravitreal injections in previous study FVF2598g or in this extension study.
Ranibizumab Treated PDT XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated PDT XO includes participants who received sham intravitreal injections in combination with photodynamic therapy in study FVF2428g or study FVF2587g before crossing over to receive ranibizumab 0.5 mg intravitreal injections in previous studies FVF2428g, study FVF2587g or this extension study.
Ranibizumab Untreated Group In this extension study participants did not receive Ranibizumab. Participants in this group were previously enrolled in one of the following studies: FVF2428g (NCT00056823), FVF2587g (NCT00061594), FVF2598g (NCT0056823) but did not receive treatment with Ranibizumab in that study or in this extension study (FVF3426g).
Total Total of all reporting groups

Baseline Measures
    RanibizumabTreated Initial Mono     RanibizumabTreated Initial + PDT     RanibizumabTreated Sham XO     Ranibizumab Treated PDT XO     Ranibizumab Untreated Group     Total  
Number of Participants  
[units: participants]
 		  526     74     116     74     63     853  
Age, Customized  
[units: participants]
 		           
50 to < 65     29     5     5     8     4     51  
65 to < 75     117     19     27     21     10     194  
75 to < 85     277     42     61     35     29     444  
>= 85     103     8     23     10     20     164  
Gender  
[units: participants]
 		           
Female     304     42     76     41     36     499  
Male     222     32     40     33     27     354  



  Outcome Measures
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1.  Primary:   Number of Participants With Ocular Adverse Events   [ Time Frame: 36 months ]
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Measure Type Primary
Measure Title Number of Participants With Ocular Adverse Events
Measure Description

Number of participants with ocular adverse events in the following categories: any adverse events, serious adverse events, adverse events leading to study discontinuation, endophthalmitis and intraocular inflammation that occurred in the study eye (the eye that received all study drug injections) and the fellow eye (other eye).

Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded.
Time Frame 36 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants treated with Ranibizumab in this extension study or in one of the previous studies.

Reporting Groups
  Description
Ranibizumab Treated Initial Mono In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Participants in this group previously received ranibizumab monotherapy (Mono), that is, ranibizumab 0.5 mg intravitreal injection alone in previous study FVF2598g or ranibizumab 0.5 mg intravitreal injection in combination with sham photodynamic therapy (PDT) in previous study FVF2587g.
Ranibizumab Treated Initial + PDT In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. This group includes participants who received ranibizumab 0.5 mg intravitreal injection in combination with photodynamic therapy in previous Study FVF2428g.
Ranibizumab Treated Sham XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated Sham Crossover (XO) includes participants who received sham intravitreal injections before crossing over to receive ranibizumab 0.5 mg intravitreal injection in previous study FVF2598g or this extension study.
Ranibizumab Treated PDT XO In this extension study participants received Ranibizumab intravitreal injection 0.5 mg in the study eye given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. Ranibizumab Treated PDT XO includes participants who received sham intravitreal injections in combination with photodynamic therapy in previous study FVF2428g or previous study FVF2587g before crossing over to receive ranibizumab 0.5 mg intravitreal injection in previous study FVF2428g, previous study FVF2587g or this extension study.

Measured Values
    Ranibizumab Treated Initial Mono     Ranibizumab Treated Initial + PDT     Ranibizumab Treated Sham XO     Ranibizumab Treated PDT XO  
Number of Participants Analyzed  
[units: participants]
 		  526     74     116     74  
Number of Participants With Ocular Adverse Events  
[units: participants]
 		       
Any adverse event in study eye     418     56     96     59  
Serious adverse events in study eye     46     2     6     2  
Adverse events led to discontinuation, study eye     7     2     3     2  
Endophthalmitis in study eye     1     0     0     0  
Intraocular inflammation in study eye, total     8     2     4     1  
Serious Intraocular inflammation in study eye     1     0     0     0  
Any adverse event in fellow eye     304     50     72     47  
Serious adverse events in fellow eye     22     4     6     3  
Adverse events led to discontinuation, fellow eye     6     7     4     3  
Endophthalmitis in fellow eye     0     0     0     0  
Intraocular inflammation in fellow eye, total     5     0     0     0  
Serious intraocular inflammation in fellow eye     1     0     0     0  

No statistical analysis provided for Number of Participants With Ocular Adverse Events



2.  Primary:   Number of Participants With Non-ocular Adverse Events   [ Time Frame: 36 months ]
  Show Outcome Measure 2

3.  Primary:   Number of Participants With Positive Serum Antibodies to Ranibizumab at Month 12 and Month 24   [ Time Frame: Month 12 and 24 ]
  Show Outcome Measure 3

4.  Secondary:   Change From Baseline in Best Corrected Visual Acuity (BCVA) at a Starting Test Distance of 2 Meters   [ Time Frame: Extension study baseline, Months 3, 6, 9, 12, 15, 18, 21 and 24 ]
  Show Outcome Measure 4

5.  Secondary:   Change From Baseline in Best Corrected Visual Acuity at a Starting Test Distance of 4 Meters   [ Time Frame: Extension study baseline, Months 12 and 24 ]
  Show Outcome Measure 5


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Genentech
Organization: Genentech
e-mail: ctg-post-d@gene.com


No publications provided


Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT00379795     History of Changes
Other Study ID Numbers: FVF3426g (Cohort 1)
Study First Received: September 21, 2006
Results First Received: April 1, 2011
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration