Clinical Trial Results:
Significance of the FSH receptor polymorphism p.N680S for the efficacy of FSH therapy of idiopathic male infertility: a pharmacogenetic approach.
Summary
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EudraCT number |
2010-020240-35 |
Trial protocol |
IT DE |
Global end of trial date |
14 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Nov 2021
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First version publication date |
18 Nov 2021
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Other versions |
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Summary report(s) |
Final Manuscript |
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 |
2010-020240-35
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Modena and Reggio Emilia
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Sponsor organisation address |
Via Campi, Modena, Italy,
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Public contact |
Manuela SImoni, University of Modena and Reggio Emilia, +39 0593961815, manuela.simoni@unimore.it
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Scientific contact |
Manuela Simoni, University of Modena and Reggio Emilia, +39 0593961815, manuela.simoni@unimore.it
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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 |
12 Sep 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Apr 2015
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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 |
In men with idiopathic infertility, the sperm DNA fragmentation index (DFI) within 12 weeks of FSH therapy and 12 weeks follow-up improves depending on the FSHR genotype as assessed by the non-synonymous SNP rs6166 (wild type or p.N680S).
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Feb 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 |
Germany: 20
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Country: Number of subjects enrolled |
Italy: 60
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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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) |
80
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The population to be studied are adult men with: - age 20-50 years - idiopathic male factor infertility for at least one year; - homozygous FSHR allele at codon 680 (wild type: Asn/Asn or Ser/Ser); - sperm DFI > 15%; - normal serum FSH levels (< 8 IU/L) - normal serum LH, testosterone, prolactin and estradiol levels - no female infertility | |||||||||||||||
Pre-assignment
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Screening details |
During the pre-assignement phase, inclusion and exclusion criteria were evaluated in all men attending the Andrological outpatients clinic for couple infertility | |||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
80 | |||||||||||||||
Number of subjects completed |
80 [1] | |||||||||||||||
Notes [1] - The number of subjects reported to be in the pre-assignment period is not consistent with the number starting period 1. It is expected that the number completing the pre-assignment period are also present in the arms in period 1. Justification: The number of patients is correctly reported |
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||
Roles blinded |
Subject | |||||||||||||||
Blinding implementation details |
The subject and the investigators were blinded for the subjects' genotype
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Group 1 | |||||||||||||||
Arm description |
Patients with FSHR p.680N>S N homozygous | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
FSH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
150 IU every other day
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Arm title
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Group 2 | |||||||||||||||
Arm description |
Patients with FSHR p.680N>S S homozygous | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
FSH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
150 IU every other day
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Period 2
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Period 2 title |
End of treatment phase
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||
Roles blinded |
Subject | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | |||||||||||||||
Arm description |
Patients with FSHR p.680N>S N homozygous | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
FSH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
150 IU every other day
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Arm title
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Group 2 | |||||||||||||||
Arm description |
Patients with FSHR p.680N>S S homozygous | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
FSH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
150 IU every other day
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | |||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Patients with FSHR p.680N>S N homozygous | ||
Reporting group title |
Group 2
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Reporting group description |
Patients with FSHR p.680N>S S homozygous | ||
Reporting group title |
Group 1
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Reporting group description |
Patients with FSHR p.680N>S N homozygous | ||
Reporting group title |
Group 2
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Reporting group description |
Patients with FSHR p.680N>S S homozygous |
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End point title |
Sperm DNA Fragmentation Index | ||||||||||||||||||||
End point description |
Sperm DNA Fragmentation Index
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End point type |
Primary
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End point timeframe |
After treatment and follow-up phases
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Statistical analysis title |
Comparison between genotypes | ||||||||||||||||||||
Statistical analysis description |
Patients were first divided according to the genotype of the rs6166 in the FSHR, forming two groups: homozygous FSHR p.N680S N and homozygous FSHR. Comparison of variables between different groups was performed by Mann-Whitney test.
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Comparison groups |
Group 1 v Group 2
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Number of subjects included in analysis |
66
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
Mann-Whitney | ||||||||||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Potential adverse events were evaluated at each visit
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Assessment type |
Non-systematic | |||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
AIFA | |||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Group 1
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Reporting group description |
- | |||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
- | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No adverse events were recorded, neither serious nor not-serious |
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/27329968 |