Clinical Trial Results:
Open-label, single-arm, Phase IV, multicenter trial to explore the immunogenicity of the liquid formulation of Saizen® in subjects with adult growth hormone deficiency (AGHD)
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Summary
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EudraCT number |
2012-004263-47 |
Trial protocol |
GB SE DE CZ |
Global end of trial date |
21 Mar 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Mar 2017
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First version publication date |
03 Mar 2017
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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 |
EMR200104-011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01806298 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck KGaA
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Center Merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.com
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Scientific contact |
Communication Center Merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.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 |
21 Mar 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Mar 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Mar 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 determine whether the marketed Saizen solution for injection, administered according to the approved label for 9 months (39 weeks) in adults with GHD, induces the development of binding antibodies (BAbs).
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
28 Jun 2013
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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 |
Australia: 31
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Country: Number of subjects enrolled |
Czech Republic: 6
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Country: Number of subjects enrolled |
Germany: 9
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Country: Number of subjects enrolled |
United Kingdom: 28
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Country: Number of subjects enrolled |
Sweden: 4
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Worldwide total number of subjects |
78
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EEA total number of subjects |
47
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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) |
76
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
First subject enrolled: 28 Jun 2013; Last subject visited on: 21 Mar 2016 | ||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Saizen® | ||||||||||||||||
Arm description |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Saizen®
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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 |
Subcutaneous use
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Dosage and administration details |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®. The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Saizen®
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Reporting group description |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®. | ||
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End point title |
Percentage of Subjects Developing Binding Antibodies (BAbs) to Saizen® [1] | ||||||||
End point description |
Percentage of subjects developing BAbs = (Number of BAb positive subjects / Total number of subjects) x 100. The modified Intent-To-Treat (mITT) analysis set included all treated subjects who had received at least 1 administration of Saizen® and had at least 1 post-baseline BAbs assessment.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 39
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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: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Binding Antibodies (BAbs) Who Became Positive for Neutralizing Antibodies (NAbs) | ||||||
End point description |
Percentage of subjects with BAbs who become positive for NAbs = (Number of NAb positive subjects / Number of BAbs positive subjects) x 100.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 39
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| Notes [2] - Data could not be analysed as there were no subjects who were BAb positive. |
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| No statistical analyses for this end point | |||||||
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End point title |
Insulin-like Growth Factor-I (IGF-I) Levels | ||||||||||||||||||||||||||||||||||||
End point description |
Growth Hormone (GH) biomarker levels were summarised by GH treatment status at study entry (that is subjects were classified as GH treatment-naïve subjects or subjects with prior GH treatment for adult growth hormone deficiency [AGHD]). The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "n" signifies those subjects who were evaluable for the specified category at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 2, 8, 16, 29, 39 and 41
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | ||||||||||||||||||||||||||||||||||||
End point description |
Growth Hormone (GH) biomarker levels were summarised by GH treatment status at study entry (that is subjects were classified as GH treatment-naïve subjects or subjects with prior GH treatment for adult growth hormone deficiency [AGHD]). The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "n" signifies those subjects who were evaluable for the specified category at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 2, 8, 16, 29, 39 and 41
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS) | ||||||||||||||||||||||||||||||||||||
End point description |
Insulin-like Growth Factor-1 SDS was calculated based on the actual value of IGF-1 minus reference value of IGF-1 divided by reference standard deviation of IGF-1. SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) a subject's value was relative to the mean of the reference population. The scores were centered around zero. Negative score indicated that the IGF-I value was lower compared to the reference population. The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "n" signifies those subjects who were evaluable for the specified category at each time point.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 41
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Treatment Adherence Rate as Documented Using EasypodTM Connect | ||||||||
End point description |
Treatment adherence rate was measured by: (total dose received divided by total dose prescribed) multiplied by 100. Saizen solution for injection was administered using the easypod device and treatment adherence information was obtained from the device using the easypod connect software. The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®.
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End point type |
Secondary
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End point timeframe |
Week 2, 8, 16, 29 and 39
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Treatment-emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | ||||||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are those events with onset dates occurring during the on-treatment period or if the worsening of an event is during the on-treatment period. TEAEs include both Serious TEAEs and non-serious TEAEs. The safety analysis set.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 41
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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 |
Baseline up to Week 41
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Adverse event reporting additional description |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
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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 |
19.0
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Reporting groups
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Reporting group title |
Saizen®
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Reporting group description |
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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31 Oct 2013 |
Modified exclusion criterion 3 to allow inclusion of subjects with adequately treated basal cell or squamous cell skin cancer. |
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15 Jul 2014 |
1) Modified inclusion criterion 5 by increasing the maximum permitted BMI level measured at the Screening visit (Weight in kilograms / [Height in meters]^2 ) from less than or equal to (<=) 35 to <= 40 kg/m^ 2 .
2) Updated administrative information to reflect the change in the Sponsor’s medical responsible, clinical trial leader and the principal statistician. |
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09 Oct 2014 |
1) Modified inclusion criterion 2 to allow recruitment of subjects with CO-AGHD as well as AO-AGHD.
2) Modified inclusion criterion 3 to allow enrollment of subjects who stopped prior GH treatment for AGHD 1 month prior to Screening as compared to at least 3 months prior to Screening previously.
3) Modified exclusion criterion 3 to ensure that the wording is in alignment with the Saizen label. Provided clarification that the presence of an active malignancy is a contraindication and that any pre-existing malignancy must be inactive with anti-tumor therapy completed prior to starting trial on Saizen therapy.
4) Updated administrative information to reflect the change in the Sponsor’s principal statistician and the central laboratory. |
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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. | |||
| None reported | |||
