Clinical Trial Results:
Role of multimodal imaging in the evaluation of anatomic alterations in neovascular Age-Related Macular Degeneration (AMD) subjects: 18 month Phase 2a open label study of Fovista™ (anti-PDGF therapy) administered in combination with anti-VEGF therapy
Summary
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EudraCT number |
2015-000519-42 |
Trial protocol |
FR IT |
Global end of trial date |
06 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Nov 2018
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First version publication date |
28 Nov 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
OPH1008
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ophthotech Corporation
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Sponsor organisation address |
One Penn Plaza, Suite 3520 , New York, United States, NY 10119
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Public contact |
Fang Li, Ophthotech Corporation, +1 212-845-8219, fang-li@ophthotech.com
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Scientific contact |
Fang Li, Ophthotech Corporation, +1 212-845-8219, fang-li@ophthotech.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jan 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jan 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the safety and biomarker responses of various regimens of Fovista™ when administered in combination with anti-VEGF agents, in treatment naïve and treatment experienced neovascular AMD subjects.
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Protection of trial subjects |
All subjects signed the informed consent before undergoing any study-related procedure.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Mar 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 15
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Country: Number of subjects enrolled |
Italy: 17
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
21
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85 years and over |
8
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Recruitment
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Recruitment details |
This study was conducted in 6 centers in France and 6 centers in Italy between 29 March 2016 and 06 January 2017. Written informed consent was obtained before any of the Screening details listed below were performed. | |||||||||||||||||||||||||
Pre-assignment
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Screening details |
Medical & ophthalmologic history, protocol refraction & visual acuity, ophthalmologic examination, Goldmann Applanation Tonometry, color fundus photographs, Fluorescein Angiograms, Optical Coherence Tomography (OCT), Indocyanine Green and OCT angiography, laboratory & pregnancy tests & concomitant medication were assessed at screening prior to Day1 | |||||||||||||||||||||||||
Period 1
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Period 1 title |
18 Months (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment naive, simultaneous regimen | |||||||||||||||||||||||||
Arm description |
Treatment naive subjects randomized to simultaneous regimen received IVT Fovista + IVT anti-VEGF agent administered on the same day. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Fovista
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Investigational medicinal product code |
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Other name |
E10030, pegpleranib
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent (i.e., Lucentis, Eylea or Avastin).
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected visual acuity (BCVA, hereafter referred to as VA) change from the prior visit.
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Investigational medicinal product name |
Avastin
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Investigational medicinal product code |
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Other name |
Bevacizumab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Avastin.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Investigational medicinal product name |
Eylea
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Eylea.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Investigational medicinal product name |
Lucentis
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Lucentis.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Arm title
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Treatment naive, pre-treatment regimen | |||||||||||||||||||||||||
Arm description |
Treatment naive subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Fovista
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
E10030, pegpleranib
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent (i.e., Lucentis, Eylea or Avastin).
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Investigational medicinal product name |
Avastin
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Investigational medicinal product code |
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Other name |
Bevacizumab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Avastin.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Investigational medicinal product name |
Eylea
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Eylea.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Investigational medicinal product name |
Lucentis
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Lucentis.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Arm title
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Treatment experienced, simultaneous regimen | |||||||||||||||||||||||||
Arm description |
Treatment experienced subjects randomized to simultaneous regimen, received IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Fovista
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
E10030, pegpleranib
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent (i.e., Lucentis, Eylea or Avastin).
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Investigational medicinal product name |
Avastin
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
Bevacizumab
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Avastin.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Investigational medicinal product name |
Eylea
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Eylea.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Investigational medicinal product name |
Lucentis
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
|
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent Lucentis.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Arm title
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Treatment experienced, pre-treatment regimen | |||||||||||||||||||||||||
Arm description |
Treatment experienced subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anit VEGF agent administered in combination on the same day. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Fovista
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
E10030, pegpleranib
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|||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||
Routes of administration |
Intravitreal use
|
|||||||||||||||||||||||||
Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent (i.e., Lucentis, Eylea or Avastin).
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
|
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Investigational medicinal product name |
Avastin
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
Bevacizumab
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Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||
Routes of administration |
Intravitreal use
|
|||||||||||||||||||||||||
Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Avastin.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
|
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Investigational medicinal product name |
Eylea
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|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||
Routes of administration |
Intravitreal use
|
|||||||||||||||||||||||||
Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Eylea.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
|
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Investigational medicinal product name |
Lucentis
|
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Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
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Routes of administration |
Intravitreal use
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Dosage and administration details |
There were 2 cohorts of subjects in this trial:treatment experienced and treatment naïve. Subjects in each cohort were randomized in a 1:1 ratio to either Simultaneous Treatment or Pre-treatment Regimen. Treatment experienced subjects continued to receive the same anti-VEGF agent that they received prior to entry into the study (i.e., Lucentis, Eylea or Avastin). Treatment naïve subjects were randomized in a 1:1:1 ratio to Lucentis, Eylea, or Avastin as the anti-VEGF agent.
Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent Lucentis.
All subjects were treated every month for the first 5 months (Baseline, Months 1,2,3,4), followed by treatment every 3 months (Months 7,10,13, and 16), for a total of 18 months. During the non-treatment months, subjects could be treated according to the best corrected VA change from the prior visit.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment naive, simultaneous regimen
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Reporting group description |
Treatment naive subjects randomized to simultaneous regimen received IVT Fovista + IVT anti-VEGF agent administered on the same day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment naive, pre-treatment regimen
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Reporting group description |
Treatment naive subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment experienced, simultaneous regimen
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Reporting group description |
Treatment experienced subjects randomized to simultaneous regimen, received IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment experienced, pre-treatment regimen
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Reporting group description |
Treatment experienced subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anit VEGF agent administered in combination on the same day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment naive, simultaneous regimen
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Reporting group description |
Treatment naive subjects randomized to simultaneous regimen received IVT Fovista + IVT anti-VEGF agent administered on the same day. | ||
Reporting group title |
Treatment naive, pre-treatment regimen
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Reporting group description |
Treatment naive subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | ||
Reporting group title |
Treatment experienced, simultaneous regimen
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Reporting group description |
Treatment experienced subjects randomized to simultaneous regimen, received IVT Fovista 1.5 mg and IVT anti-VEGF agent administered in combination on the same day. | ||
Reporting group title |
Treatment experienced, pre-treatment regimen
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Reporting group description |
Treatment experienced subjects randomized to pre-treatment regimen received initial administration of IVT Fovista 1.5 mg monotherapy and 48 hours later (2 days) followed by the administration of IVT Fovista 1.5 mg and IVT anit VEGF agent administered in combination on the same day. |
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End point title |
Change in Visual Acuity [1] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Severe Visual Acuity Loss (Proportion of subjects with >15 letter loss at Months 12 and 18)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study was terminated early. Due to the small number of subjects enrolled and treated in the study, summary statistics of change in visual acuity over time was not conducted. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From Randomization at Day 1 (14 days after Screening) until end of study.
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Adverse event reporting additional description |
AEs were reported on the safety population (all subjects who received at least 1 dose of study drug [Fovista]).Causally related occurrences included both events reported as: related to injection procedure and related to study drug.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Treatment naive, simultaneous regimen
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Reporting group description |
Treatment naive cohort, simultaneous regimen. Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent (i.e., Lucentis, Eylea or Avastin). | |||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment naive, pre-treatment regimen
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Reporting group description |
Treatment naive cohort, pre-treatment regimen. Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent (i.e., Lucentis, Eylea or Avastin). | |||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment experienced, simultaneous regimen
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Reporting group description |
Treatment naive cohort, simultaneous regimen. Subjects received the Fovista injection first (1.5 mg/eye), followed by the anti-VEGF agent (i.e., Lucentis, Eylea or Avastin). | |||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment experienced,pre-treatment regimen
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Reporting group description |
Treatment naive cohort, pre-treatment regimen. Subjects received IVT Fovista (1.5 mg/eye) monotherapy and 48 hours later, IVT Fovista (1.5 mg/eye) in combination with anti-VEGF agent (i.e., Lucentis, Eylea or Avastin). | |||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Oct 2015 |
The rationale for the changes incorporated in OPH1008 Amendment A was with regard to the number of study visits where the “pre-treatment” regimen was administered. The original OPH1008 protocol design included the “pre-treatment” regimen administered at all study visits after the Induction Phase. Amendment A modified the treatment schedule to administer the “pre-treatment” regimen for the first 5 months of the study (Baseline, Month 1-Month 4). Beginning at Month 5, subjects were to be administered the simultaneous treatment regimen only. The “pre-treatment” regimen was now only administered during the Induction Phase of the study. In addition to the changes described above, a clarification to one of the inclusion criteria was made. There was also a change in the company responsible for Data management. |
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10 Jun 2016 |
Amendment B included the update of the ophthalmic inclusion criteria. The definition of active CNV was modified to remove requirement for fluid as objective of protocol was to assess biomarker responses of various regimens of Fovista™ when administered in combination with anti-VEGF agents.
Using Snellen acuity before and after the prior anti-VEGF therapy maintains consistent visual acuity assessment, avoiding the potential for changes in visual acuity due to testing conditions.
Amendment B included the update of both ophthalmic inclusion and exclusion criteria with respect to the requirement for number of prior intravitreal injections, criteria were modified to be consistent with European labeling of anti-VEGF agents where up to 3 loading doses are required.
In addition, the exclusion criterion for HbA1c value ≥ 6.5% was removed as the safety profile in subjects with high HbA1c values was unremarkable. Only subjects with definitive diagnosis of diabetes mellitus or diabetic retinopathy were to be excluded.
The section of the protocol concerning previous and concomitant therapy was modified to reflect the changes in the inclusion and exclusion criteria with respect to the requirement for number of prior intravitreal injections (modified to be consistent with European labeling of anti-VEGF agents where up to 3 loading doses are required). The amendment also included corrections in the text of the protocol and other administrative |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The study was terminated early (due to the lack of efficacy from two controlled phase 3 studies [OPH1002 and OPH1003]) after the enrollment and treatment of 32 subjects, no subject completed the 18-month study. |