Clinical Trial Results:
A phase 2b randomized, double-masked, controlled trial to establish the safety and efficacy of intravitreous administration of Fovista™ (Anti-PDGFBB pegylated aptamer) administered in combination with Avastin® compared to Avastin® monotherapy in subjects with subfoveal neovascular age-related macular degeneration.
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Summary
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EudraCT number |
2015-000518-23 |
Trial protocol |
NL EE CZ HR |
Global end of trial date |
25 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 |
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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 |
OPH1007
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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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 |
25 Jan 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
25 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 |
The objectives of this study are to evaluate the safety and efficacy of Fovista (E10030 or pegpleranib) intravitreous administration when administered in combination with Avastin compared to Avastin monotherapy in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).
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Protection of trial subjects |
All subjects signed the informed consent before undergoing any study-related procedure. An independent data monitoring committee reviewed subject safety data during the course of the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Apr 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Netherlands: 7
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Country: Number of subjects enrolled |
Czech Republic: 19
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Country: Number of subjects enrolled |
Estonia: 3
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Worldwide total number of subjects |
29
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EEA total number of subjects |
29
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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) |
2
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From 65 to 84 years |
25
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85 years and over |
2
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Recruitment
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Recruitment details |
This study was conducted at 6 centers in 3 countries between 26 April 2016 and 25 January 2017. Written informed consent was obtained before any of the Screening details listed below were performed. | |||||||||||||||
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Pre-assignment
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Screening details |
Medical&ophthalmologic history,protocol refraction&visual acuity,ophthalmologic examination,Goldmann Applanation Tonometry,vital signs,physical examination, performance status,ECG,color fundus photographs,Fluorescein Angiograms,Optical Coherence Tomography,laboratory&pregnancy tests&concomitant medication were assessed at screening prior to Day1 | |||||||||||||||
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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 |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Assessor | |||||||||||||||
Blinding implementation details |
It was the responsibility of the Principal Investigator to ensure that the physician assessing AEs, the VA examiner, all masked study personnel, and the subject remained masked to the subject’s treatment assignment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fovista + Avastin | |||||||||||||||
Arm description |
Subjects received the Avastin injection first, followed by Fovista injection. | |||||||||||||||
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 |
Subjects received the Avastin injection first (1.25 mg/eye), followed by the Fovista injection (1.5 mg/eye). Both active study drugs were administered as intravitreal injections. Subjects randomized to Fovista+Avastin received between 12 and 18 injections of Avastin 1.25 mg/eye and Fovista 1.5 mg/eye.
Subjects were treated with study treatment, IVT Fovista in combination with IVT Avastin, every month for the first 6 doses (Day 1, Months 1, 2, 3, 4, and 5) and every other month thereafter (i.e., every 2 months: Months 7, 9, 11, 13, 15, and 17). 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 |
Subjects received the Avastin injection first (1.25 mg/eye), followed by the Fovista injection (1.5 mg/eye). Both active study drugs were administered as intravitreal injections. Subjects randomized to Fovista+Avastin received between 12 and 18 injections of Avastin 1.25 mg/eye and Fovista 1.5 mg/eye.
Subjects were treated with study treatment, IVT Fovista in combination with IVT Avastin, every month for the first 6 doses (Day 1, Months 1, 2, 3, 4, and 5) and every other month thereafter (i.e., every 2 months: Months 7, 9, 11, 13, 15, and 17). 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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Sham + Avastin | |||||||||||||||
Arm description |
Subjects received the Avastin injection first, followed by a Sham injection (pressure applied at the would-be injection site with a needle-less syringe hub). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
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 |
Injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
Subjects received the Avastin injection first (1.25 mg/eye), followed by a Sham injection (pressure applied at the would-be injection site with a needle-less syringe hub). Avastin was administered as intravitreal injections. Subjects randomized to Sham+Avastin received between 12 and 18 injections of Avastin 1.25 mg/eye.
Subjects were treated with study treatment, Sham in combination with IVT Avastin, every month for the first 6 doses (Day 1, Months 1, 2, 3, 4, and 5) and every other month thereafter (i.e., every 2 months: Months 7, 9, 11, 13, 15, and 17). During the non-treatment months, subjects could be treated according to the VA change from the prior visit.
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Baseline characteristics reporting groups
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Reporting group title |
Fovista + Avastin
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Reporting group description |
Subjects received the Avastin injection first, followed by Fovista injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sham + Avastin
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Reporting group description |
Subjects received the Avastin injection first, followed by a Sham injection (pressure applied at the would-be injection site with a needle-less syringe hub). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fovista + Avastin
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Reporting group description |
Subjects received the Avastin injection first, followed by Fovista injection. | ||
Reporting group title |
Sham + Avastin
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Reporting group description |
Subjects received the Avastin injection first, followed by a Sham injection (pressure applied at the would-be injection site with a needle-less syringe hub). | ||
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End point title |
Mean change in visual acuity (ETDRS letters) from baseline at the Month 18 visit. [1] | ||||||||||||
End point description |
The primary efficacy endpoint was the mean change in visual acuity (ETDRS letters) from baseline at the Month 18 visit.
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End point type |
Primary
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End point timeframe |
Baseline at the Month 18 visit.
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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 1dose of study drug
[Fovista,Avastin or Sham]). Subjects who have ever received an injection of Fovista were analyzed in
the Fovista+Avastin group.Causally related occurrences included both events reported as: related to
injection procedure and related to study drug
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Fovista +Avastin
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Reporting group description |
From Randomization at Day 1 (14 days after Screening) until end of study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sham + Avastin
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Reporting group description |
Subjects received the Avastin injection first, followed by a Sham injection (pressure applied at the would-be injection site with a needle-less syringe hub). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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. | |||
| Due to the early termination of the study and small number of subjects randomized and treated (N=29), none of the efficacy analyses (primary and secondary endpoints) planned in the protocol were conducted. | |||
