Clinical Trial Results:
Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation: AfterDmab
Summary
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EudraCT number |
2016-000852-91 |
Trial protocol |
NL |
Global end of trial date |
01 Feb 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Feb 2021
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First version publication date |
14 Feb 2021
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Other versions |
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Summary report(s) |
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 |
W15.032
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02499237 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
LUMC
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Sponsor organisation address |
albinusdreef 2, leiden, Netherlands,
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Public contact |
Clinical Research Internal Medicine, Leiden University Medical Center, research_interne@Lumc.nl
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Scientific contact |
Clinical Research Internal Medicine, Leiden University Medical Center, research_interne@Lumc.nl
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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 |
05 Apr 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Feb 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Feb 2020
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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 changes in BMD of the lumbar spine (LS) one year after treatment discontinuation in denosumab-treated women and in denosumab-treated women who received a single infusion of zoledronic acid one year before treatment discontinuation
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Protection of trial subjects |
NR
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 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 |
Netherlands: 15
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Country: Number of subjects enrolled |
Greece: 60
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Worldwide total number of subjects |
75
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EEA total number of subjects |
75
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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) |
45
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From 65 to 84 years |
30
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85 years and over |
0
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Recruitment
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Recruitment details |
recruitment at the FLS from the Leiden University Medical Center from 25/10/2016 till 01-02-2018 | |||||||||||||||
Pre-assignment
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Screening details |
as stated in summary | |||||||||||||||
Period 1
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Period 1 title |
25/10/2016 till 01-02-2018 (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
not blinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Zoledronate | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
zoledronate
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
5 mg iv
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Arm title
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none | |||||||||||||||
Arm description |
no active treatment | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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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: query not clear |
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Baseline characteristics reporting groups
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Reporting group title |
25/10/2016 till 01-02-2018
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
zol
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The trial required 56 patients to have a power of 95% to detect a 6% difference in LS-BMD between the two treatment groups with a two-sided error α probability of 0.05. Data for continuous variables are presented as mean ± standard error of the mean (SEM). Data for categorical variables are presented as number and/or frequencies. Kolmogorov-Smirnov test was used to test the normality of distribution of continuous variables. Within group comparisons of continuous variables were performed with repeated measures analysis of variance (ANOVA) or Friedman test. In case of statistically significant trend, multiple pairwise comparisons were performed with Bonferroni post-hoc adjustment. Independent T-test or Mann-Whitney test were used to compare continuous variables between groups. Chi-square or Fischer’s exact test were used for comparisons of categorical variables between groups. Spearman’s (rs) coefficient of correlation was used for bivariate correlations between continuous variables. A
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Subject analysis set title |
no
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
see protocol
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End points reporting groups
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Reporting group title |
Zoledronate
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Reporting group description |
- | ||
Reporting group title |
none
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Reporting group description |
no active treatment | ||
Subject analysis set title |
zol
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The trial required 56 patients to have a power of 95% to detect a 6% difference in LS-BMD between the two treatment groups with a two-sided error α probability of 0.05. Data for continuous variables are presented as mean ± standard error of the mean (SEM). Data for categorical variables are presented as number and/or frequencies. Kolmogorov-Smirnov test was used to test the normality of distribution of continuous variables. Within group comparisons of continuous variables were performed with repeated measures analysis of variance (ANOVA) or Friedman test. In case of statistically significant trend, multiple pairwise comparisons were performed with Bonferroni post-hoc adjustment. Independent T-test or Mann-Whitney test were used to compare continuous variables between groups. Chi-square or Fischer’s exact test were used for comparisons of categorical variables between groups. Spearman’s (rs) coefficient of correlation was used for bivariate correlations between continuous variables. A
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Subject analysis set title |
no
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
see protocol
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End point title |
lumbale spine | |||||||||||||||||||||||||
End point description |
see summary
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End point type |
Primary
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End point timeframe |
24 months
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Statistical analysis title |
analyses | |||||||||||||||||||||||||
Statistical analysis description |
see protocol
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Comparison groups |
Zoledronate v none v zol v no
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Number of subjects included in analysis |
117
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||
P-value |
≤ 0.05 | |||||||||||||||||||||||||
Method |
ANOVA | |||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||
Point estimate |
1
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.5 | |||||||||||||||||||||||||
upper limit |
1 | |||||||||||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
2
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Adverse events information
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Timeframe for reporting adverse events |
during the trial
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Assessment type |
Systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||
Dictionary version |
2
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Reporting groups
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Reporting group title |
patients
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Reporting group description |
- | ||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||
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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 |