Clinical Trial Results:
An open label, multiple dose, Phase III clinical study in patients with prostate cancer to investigate the clinical efficacy of AMW goserelin 3.6 mg implant in its application system
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Summary
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EudraCT number |
2014-002484-15 |
Trial protocol |
DE |
Global end of trial date |
25 May 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Sep 2021
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First version publication date |
10 Sep 2021
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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 |
AMW/004/C
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AMW GmbH
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Sponsor organisation address |
Birkerfeld 11, Warngau, Germany, 83627
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Public contact |
Chief Executive Officer, AMW GmbH, +49 80244709990, info@a-m-w.eu
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Scientific contact |
Kerstin Hofmann, Head Clinical Research Department, AMW GmbH, +49 80244709990, k.hofmann@a-m-w.eu
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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 |
18 Aug 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 May 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
25 May 2016
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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 |
• To investigate the efficacy of goserelin 3.6 mg implant (when applied every 28 days for 56 days) in suppression of testosterone levels below castrate level (0.5 ng/ml). The study will be considered a successful bridging study, if the response rate, i.e., the percentage of patients with plasma testosterone levels below castrate level (0.5 ng/ml) on Days 28 and 56 (at Visits 4 and 6), will be at least 90% in the patients of the modified full analysis set (see Primary efficacy endpoint).
• To demonstrate correct functionality of the application system, as assessed by an increase of plasma goserelin levels to a value above the Lower Limit of Quantification (LLOQ) (i.e., presence of goserelin in plasma) and as assessed by the investigator with confirmation by a witness.
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Protection of trial subjects |
close monitoring of all subjects during the study including safety monitoring:
• Findings from digital rectal examination of the prostate,
• Adverse Events (AEs),
• Vital signs (blood pressure, heart rate), body weight and temperature,
• Safety laboratory parameters
• local tolerability of the implant
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Background therapy |
- | ||
Evidence for comparator |
This is a single arm, non-comparative study. | ||
Actual start date of recruitment |
13 Jan 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 |
Germany: 33
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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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) |
4
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From 65 to 84 years |
26
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85 years and over |
3
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Recruitment
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Recruitment details |
Overall, 36 patients were screened for the study. Three patients were screening failures. 33 patients were considered eligible at baseline and received study medication. Two clinical sites in Germany were involved in recruitment. | ||||||
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Pre-assignment
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Screening details |
Screening procedures were performed up to 2 weeks prior application of the first implant: - Informed Consent - Demography, Medical history, concomitant diseases - Concomitant medications - Inclusion/ Exclusion criteria - full physical examination - Body weight, sublingual temperature - Vital signs - Safety lab - Testosteron determination | ||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
uncontrolled, open label
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Arms
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Arm title
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Application Goserelin 3.6 mg implant | ||||||
Arm description |
Two subcutaneous applications of AMW Goserelin 3.6 mg implant, on Day 0 and on Day 28 (total duration of treatment 56 days) | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
AMW Goserelin 3.6 mg Implantat
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Investigational medicinal product code |
C0005AMW0802IMP
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Other name |
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Pharmaceutical forms |
Implant
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Goserelin 3.6 mg implant was injected by a physician subcutaneously into the anterior abdominal wall at Day 0 and Day 28 according to the application instruction provided. Assessments concerning the applicator and its (correct) functionality was be made, a witness observed and also assessed the preparation for injection and the actual injection.
In case the applicator failed the initial visual inspection or showed signs of non- functioning during preparation, injection or after injection, another applicator had to be used if necessary to achieve a successful implantation. Details had to be documented in the CRF and had to be reported to the CRO and the sponsor immediately. Any defective applicator had be sent to the sponsor for inspection as soon as possible. The duration of treatment in this study was two months (56 days) with two applications of goserelin.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
all patients who received two subcutaneous applications of AMW Goserelin 3.6mg implant on day 0 and day 28 (total duration 56 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
33 patients were considered eligible at baseline and received study medication. These 33 patients were analysed i in the full analysis set (FAS). Additionally, a subset of the full analysis set (modified full analysis set, MFAS) was analysed, comprising all FAS patients for whom two injection times were documented in the case report form (CRF) and who did not terminate the study prematurely for reasons not causally related to lack of efficacy or safety of study medication. All 33 patients of the FAS were also included in the MFAS.
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Subject analysis set title |
Per Protocol (PP)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The PP analysis set comprised 29 patients treated with study medication and without major protocol violations.
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End points reporting groups
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Reporting group title |
Application Goserelin 3.6 mg implant
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Reporting group description |
Two subcutaneous applications of AMW Goserelin 3.6 mg implant, on Day 0 and on Day 28 (total duration of treatment 56 days) | ||
Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
33 patients were considered eligible at baseline and received study medication. These 33 patients were analysed i in the full analysis set (FAS). Additionally, a subset of the full analysis set (modified full analysis set, MFAS) was analysed, comprising all FAS patients for whom two injection times were documented in the case report form (CRF) and who did not terminate the study prematurely for reasons not causally related to lack of efficacy or safety of study medication. All 33 patients of the FAS were also included in the MFAS.
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Subject analysis set title |
Per Protocol (PP)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP analysis set comprised 29 patients treated with study medication and without major protocol violations.
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End point title |
Percentage of patients with plasma testosterone below castrate level (0.5 ng/mL) at Visit 4 (Day 28) and visit 6 (day 56) [1] | ||||||||||||
End point description |
A patient was considered a responder (response = ‘yes’), if both relevant values were below castrate level. If at least one of the two relevant values was equal to or above castrate level (i.e., ≥ 0.5 ng/mL), the patient was considered a non-responder (response = ‘no’). If at least one of the two relevant values was missing, the patient was also considered a non-responder (response = ‘no’, conservative approach).
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End point type |
Primary
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End point timeframe |
visit 4 (day 28) and visit 6 (day 56)
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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 primary endpoint was the percentage of patients with plasma testosterone below castrate level (0.5 ng/mL) at Visit 4 (Day 28) and visit 6 (day 56). In the FAS the percentage of patients with testosterone below castrate level at Visit 4 (Day 28) and Visit 6 (Day 56) (= response rate) was 93.94% with the corresponding exact 95% CI (79.77%; 99.26%). As the response rate was ≥90%, the study is considered a successful bridging study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of patients with an increase in plasma goserelin levels at Visit 3 (Day 14) and Visit 5 (Day 42) to a value above LLOQ | ||||||||||||
End point description |
Goserelin plasma levels are summarised by visit and are listed by patient. The arithmetic mean including standard deviation and the median of goserelin plasma levels measured by LC- MS/MS at Visits 3 to 6for the FAS and PP set. From Visit 3 (Day 14) on, all mean and median values of goserelin plasma levels were above the LLOQ (0.200 ng/mL) in the FAS and in the PP set. The highest arithmetic mean and median values of goserelin plasma levels were detected at Visit 3 (Day 14) and Visit 5 (Day 42) in both analysis sets. At the end of the first and and second treatment cycle, i.e. at Visit 4 (Day 28) and Visit 6 (Day 56), arithmetic mean values and median values were still above the LLOQ of 0.200 ng/mL.
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End point type |
Secondary
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End point timeframe |
visit 3 (day 14) and visit 5 (day 42)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of applications with correct functionality of the application system | ||||||||||||
End point description |
Correct functionality of the application system of the implant at baseline (Day 0) and Visit 4 (Day 28) and percentage of applications with correct functionality of the application system. Data for correct functionality of the application system plus assessment by investigator and assessment by witness and initial visual inspection of the applicator.
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End point type |
Secondary
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End point timeframe |
Visit 2 (study day 0, application implant) and visit 4 (day 28)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of patients with an increase in plasma goserelin at Visit 3 (Day 14) to a value above LLOQ | ||||||||||||
End point description |
The percentage of patients with an increase in plasma goserelin levels at Visit 3 (Day 14) to a value above LLOQ. A patient was considered to fulfil this criterion, if the goserelin value was above LLOQ at Visit 3 (Day 14) and higher than the goserelin value at the previous visit, i.e. Visit 2 (Day 0). Goserelin was assumed to be <LLOQ at Visit 2 (Day 0). Therefore, a value >LLOQ at Visit 3 (Day 14) reflects an increase compared to the previous visit.
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End point type |
Secondary
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End point timeframe |
visit 3 (day 14)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of patients with an increase in plasma goserelin at Visit 5 (Day 42) to a value above LLOQ (i.e., presence of goserelin in plasma) | ||||||||||||
End point description |
The percentage of patients with an increase in plasma goserelin levels at Visit 5 (Day 42) to a value above LLOQ (0.200 ng/mL). A patient was considered to fulfil this criterion, if the goserelin value was above LLOQ at Visit 5 (Day 42) and higher than the goserelin value at the previous visit, i.e. Visit 4 (Day 28).
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End point type |
Secondary
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End point timeframe |
visit 5 (day 42)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of patients with plasma testosterone below castrate level (0.5 ng/mL) at Visit 4 (Day 28) | ||||||||||||
End point description |
The percentage of patients with plasma testosterone levels below castrate level (0.5 ng/mL) at Visit 4 (Day 28)
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End point type |
Secondary
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End point timeframe |
visit 4 (day 28)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of patients with plasma testosterone below castrate level (0.5 ng/mL) at Visit 6 (Day 56) | ||||||||||||
End point description |
The percentage of patients with plasma testosterone levels below castrate level (0.5 ng/mL) at Visit 6 (Day 56).
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End point type |
Secondary
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End point timeframe |
visit 6 (day 56)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Testosterone levels at baseline at Visit 2 (Day 0), Visit 4 (Day 28) and at Visit 6 (Day 56) | ||||||||||||||||
End point description |
Testosterone plasma levels are summarised by visit and are listed by patient. The arithmetic mean including standard deviation and the median of testosterone plasma levels measured by LC- MS/MS at baseline Visit 2 (Day 0), Visit 4 (Day 28), and Visit 6 (Day 56) are reported for the FAS and PP set.
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End point type |
Secondary
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End point timeframe |
Visit 2 (day 0), visit 4 (day 28) and visit 6 (56)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Goserelin plasma levels at Visit 3 (Day 14) and Visit 5 (Day 42) | ||||||||||||||||
End point description |
Goserelin plasma levels are summarised by visit and are listed by patient The arithmetic mean including standard deviation and the median of goserelin plasma levels measured by LC- MS/MS at Visits 3 (Day 14) and 5 (Day 42) are summarised for the FAS and PP set.
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End point type |
Secondary
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End point timeframe |
visit 3 (day 14) and visit 5 (day 42)
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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 |
Visit 2 (study day 0, application of implant) to visit 6 (study day 56)
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Adverse event reporting additional description |
AEs were coded using MedDRA and were summarized by SOC and PT. All AEs were listed in by patient listings. The following categories were analysed using summary tables presenting absolute and relative frequencies: treatment-emergent AEs, SAEs, deaths, causally related AEs and AEs leading to discontinuation.
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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 |
19.0
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Reporting groups
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Reporting group title |
study safety analysis set
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Reporting group description |
group includes all patients with applied implants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
