Clinical Trial Results:
A Phase IIIb, Multinational, Multicenter, Open-Label Extension Study Assessing the Long-Term Safety of PRN Intravitreal Injections of DE-109 in Subjects with Non-Infectious Uveitis of the Posterior Segment of the Eye Who Have Participated in the SAKURA Development Program
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Summary
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EudraCT number |
2014-004042-96 |
Trial protocol |
DE AT IT |
Global end of trial date |
01 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Jun 2019
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First version publication date |
21 Jun 2019
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Other versions |
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Summary report(s) |
SPRING_Result Summary |
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 |
32-009
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02251938 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Santen Inc.
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Sponsor organisation address |
6401 Hollis Street, Suite 125, Emeryville, CA, United States, 94608
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Public contact |
Abu Abraham, M.D., Vireous & Retina Therapeutic Area Strategy, Santen Inc., 001 4152689161,
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Scientific contact |
Abu Abraham, M.D., Vireous & Retina Therapeutic Area Strategy, Santen Inc., 001 4152689161,
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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 |
16 Jul 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Nov 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Nov 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objective of this extension study is to evaluate the long-term safety of treatment with DE-109 (440 μg) in subjects with non-infectious uveitis of the posterior segment of the eye who have participated in the SAKURA development program.
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Protection of trial subjects |
The study was conducted in accordance with the study protocols, Good Clinical Practice (GCP) as required by US Food and Drug Administration regulations, International Council on Harmonization (ICH) guidelines, and Santen’s standard operating procedures (SOPs) for clinical investigation. Compliance with these requirements is consistent with the ethical principles that have their origins in the Declaration of Helsinki.
The ICF was written in compliance with US Title 21 CFR Part 50, ICH guidelines, and other national regulations as appropriate.The Principal Investigator (PI) or his/her designee discussed the purpose and pertinent details of the study with each subject. The ICF was approved by the governing IRB. Prior to undergoing any study related activity or administration of the study medication, a subject understood, signed, and dated the IRB-approved ICF. The subject’s signature was witnessed by the individual administering informed consent. If the PI administered the informed consent, then the subject’s signature was witnessed by another individual (e.g., member of study site staff). The PI signed and dated the ICF where designated.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2015
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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 |
United States: 33
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Country: Number of subjects enrolled |
India: 17
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Country: Number of subjects enrolled |
Turkey: 5
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
Italy: 2
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Worldwide total number of subjects |
60
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EEA total number of subjects |
5
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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) |
56
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From 65 to 84 years |
3
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85 years and over |
1
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Recruitment
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Recruitment details |
As this was an extension study, the study population was the subjects with non-infectious uveitis of the posterior segment who received clinical benefit from treatment with DE-109 as determined by the investigator. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects who were randomized and received at least two injections of DE-109 during the first 5 months of the SAKURA study and obtained clinical benefit from the study medication, as determined by the Investigator, were eligible for entry in this 12-month extension study. | ||||||||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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440 μg DE-109 | ||||||||||||||||||||
Arm description |
There was only 1 treatment group in this extension study: 440 μg DE-109. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Sirolimus
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Investigational medicinal product code |
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Other name |
DE-109
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Pharmaceutical forms |
Intraocular instillation solution
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
Study drug was administered as an intravitreal injection in the clinic.
The Investigator was not required to administer DE-109 at any visit. DE-109 treatments were given as needed, at the discretion of the Investigator and to be administered only by the Investigator; however, DE-109 treatments were not given more frequently than every 60 days.
A subject could have received treatment with DE-109 (440 μg) on Day 1 and/or any of the Post-Baseline PRN Treatment Visits based on the Investigator’s standard clinical procedures.
DE-109 was not administered at an unscheduled visit.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
440 μg DE-109
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Reporting group description |
There was only 1 treatment group in this extension study: 440 μg DE-109. | ||
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End point title |
Best Corrected Visual Acuity [1] | ||||||||||
End point description |
Change from Baseline at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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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: No statistical hypothesis testing was conducted on any parameter. |
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End point title |
Intraocular Pressure [2] | ||||||||||
End point description |
Change from Baseline at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [2] - 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: No statistical hypothesis testing was conducted on any parameter. |
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End point title |
Indirect Ophthalmoscopy: Choroid [3] | ||||||||||||||
End point description |
Shift from Baseline in Status at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [3] - 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: No statistical hypothesis testing was conducted on any parameter. |
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End point title |
Vitreous Haze [4] | ||||||||||
End point description |
Changes from baseline in VH scores at Month 12
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [4] - 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: No statistical hypothesis testing was conducted on any parameter. |
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End point title |
Rescue Therapy [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [5] - 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: No statistical hypothesis testing was conducted on any parameter. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Indirect Ophthalmoscopy: Macula [6] | ||||||||||||||
End point description |
Shift from Baseline in Status at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [6] - 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: No statistical hypothesis testing was conducted on any parameter. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Indirect Ophthalmoscopy: Optic Nerve [7] | ||||||||||||||
End point description |
Shift from Baseline in Status at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [7] - 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: No statistical hypothesis testing was conducted on any parameter. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Indirect Ophthalmoscopy: Retina [8] | ||||||||||||||
End point description |
Shift from Baseline in Status at Month 12 in the Study Eye
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End point type |
Primary
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End point timeframe |
Study assessments were conducted for all subjects at Day 1 (Baseline), Month 2, Month 4, Month 6, Month 8, Month 10, and Month 12.
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| Notes [8] - 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: No statistical hypothesis testing was conducted on any parameter. |
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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 |
During the study
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
overall trial
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Reporting group description |
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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. | |||
| None reported | |||
