Clinical Trial Results:
A single arm open label study to evaluate the pharmacodynamics and safety of a 4-week treatment with BI 144807 in patients with newly diagnosed wet age-related macular degeneration (wAMD).
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Summary
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EudraCT number |
2013-004567-30 |
Trial protocol |
HU DE AT |
Global end of trial date |
09 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Apr 2016
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First version publication date |
23 Apr 2016
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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 |
1313.20
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02121522 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
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Public contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.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 |
26 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Mar 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Apr 2015
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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 primary objective of study 1313.20 was to investigate the effect of BI 144807 on central 1-mm retinal thickness (CRT) as assessed by spectral domain optical coherence tomography (SD-OCT) in patients with newly diagnosed wAMD.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Jun 2014
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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 |
Austria: 8
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Country: Number of subjects enrolled |
Germany: 9
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Country: Number of subjects enrolled |
Hungary: 13
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
6
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From 65 to 84 years |
22
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85 years and over |
2
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Recruitment
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Recruitment details |
This is a open-label, single-arm, 4-week proof-of-concept study. | ||||||||||
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Pre-assignment
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Screening details |
All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated. In this study,30 subjects enrolled and 14 subjects treated. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (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 | ||||||||||
Blinding implementation details |
This is a Non-randomised, not controlled and open-label study.
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Arms
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Arm title
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BI 144807 | ||||||||||
Arm description |
Subjects were orally administered with 400 mg film coated tables twice daily (two tablets of 200 mg twice daily). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
BI 144807
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects were orally administered with BI 144807 400 mg film coated tables twice daily (two tablets of 200 mg twice daily).
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on the patients who were treated after successfully completing the screening period and received at least one dose of the trial medication. |
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Baseline characteristics reporting groups
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Reporting group title |
BI 144807
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Reporting group description |
Subjects were orally administered with 400 mg film coated tables twice daily (two tablets of 200 mg twice daily). | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BI 144807
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Reporting group description |
Subjects were orally administered with 400 mg film coated tables twice daily (two tablets of 200 mg twice daily). | ||
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End point title |
Change from baseline in CRT as measured by SD-OCT on day 29 [1] | ||||||||
End point description |
Change from baseline in central 1-mm retinal thickness (CRT) as measured by spectral domain optical coherence tomography (SD-OCT) on day 29.
Missing values are imputed by the worst observation carried forward (WOCF) measurement (including baseline).
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End point type |
Primary
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End point timeframe |
Baseline (day 1) and day 29
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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: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis test were tested. |
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| Notes [2] - Treated set (WOCF) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline in neovascular leakage area as assessed by FA on day 29 | ||||||||
End point description |
Change from baseline in neovascular leakage area as assessed by Fluorescein angiography (FA) on day 29. Baseline is defined as the last value collected before the first trial drug intake. Data collected after start of wet age-related macular degeneration (wAMD) therapy are set to missing.
Observed Case (OC): This method analysed only available data that were observed while patients were on treatment, ie., missing data were not imputed.
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End point type |
Secondary
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End point timeframe |
Baseline and day 29
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| Notes [3] - Treated set (OC) |
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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 first drug administration until 5 days after last drug administration, up to 5 weeks.
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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 |
18.0
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Reporting groups
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Reporting group title |
BI 144807
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Reporting group description |
Subjects were orally administered with 400 mg film coated tables twice daily (two tablets of 200 mg twice daily). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Jun 2014 |
By Amendment 1 the assessment of lesion size by FA over time (absolute and as change from baseline) was added as further efficacy endpoint. Further, it was clarified that cancers of newhistology or exacerbation of an existing cancer were always considered an SAE. Inhaled corticosteroids were not permitted as concomitant therapy. It was clarified that informed consent for PK evaluations of the eye could be obtained after Visit 1 but prior to aqueous humour sampling and that the last PK sample for plasma evaluation was to be taken at Visit 7. Moreover, it was specified that myopia of more than 8 diopters in the study eye is an exclusion criterion also if corrected by laser operation (Exclusion Criterion 1) and it was clarified that cardiac conditions as exclusion criterion also include tachycardia (Exclusion Criterion 16). In addition, the wording “known allergy to fluorescein sodium for injection“ in Exclusion Criterion 6 was changed to “known allergy or contra-indication to contrast agents employed in study”. It was added that before Visit 6 the administration times of the preceding two days are to be recorded. In the section on the definition of AESIs (Section 9.5.3.2.1), QTc was precisely defined as QTcF prolongation. It was added that thyroid stimulating hormone (TSH) was measured at the screening visit. It was detailed that in addition to the AE reports of the investigator, quantitative ECG data and qualitative findings in ECGs will be transferred from the VRC and analysed; the VCR will also provide indicators for the readability of the ECGs. Quantitative and qualitative ECG data from the ECG reading centre were reported descriptively. |
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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 trial was prematurely discontinued as the preliminary data showed that the likelihood to meet the trial’s primary efficacy endpoint would have been low even if the patient recruitment had been continued. | |||
