E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021929 |
E.1.2 | Term | Infertility male |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this intervention is to investigate whether Denosumab can improve semen quality of infertile men |
Formålet med interventionen er at undersøge om Denosumab kan bedre sædkvaliteten hos den infertile mand |
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E.2.2 | Secondary objectives of the trial |
differences in clinical pregnancies, Inhibin B, DNA fragmentation in spermatozoa, differences in semen quality |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men > 18 years of age refered due to infertility in need for further investigation with Sperm count > 0,05 mio./ml. The men have either sperm count <15 mio./ml or <40 % motile spermatozoer (A) or <4 % morphological normale spermatozoer (strict criteria)
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E.4 | Principal exclusion criteria |
Men with chronic diseases (diabetes mellitus, thyroid disease, endocrine diseases requirering treatment, malignant diseases or diseases known to be affected by- or interfere with vitamin D supplements (granulomatous diseases such as sarcoidosis, tuberculosis, wegeners, vasculitis as well as inflammatory bowel diseases e.g. chron’s disease or ulcerative colitis etc). Men with active or previous malignant disease Any case with indication for tesis biopsy, Serum ionized calcium < 1,15 mmol/l Total calcium < 2.14 mmol/l Poor dental status og dental implants Men with obstructive oligospermia or who has been vasectomized Serum Inhibin B < 30 pg/ml Abnormal karyotype
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in semen production (total motile spermatozoa, progressive motile spermatozoa, spermatozoa-count, spermatozoa-concentration) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Respectively 80 days and 160 days after intervention |
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E.5.2 | Secondary end point(s) |
Change in semen quality (-motility, -morphology og semenvolume) Change in DNA fragmentation (DFI) in spermatozoa Change in serum Inhibin-B conc. Change in serum levels of reproductive hormonea (FSH, LH, AMH, testosterone, estradiol, SHBG and prolactin) Change in bone mineral density evaluated by DXA. Change in serum level of inactive vitamin D, 1,25(OH)2D3, 25-OHD3, 24,25(OH)2D3, PTH, alkaline phosphatase, ionized calcium, phosphate, FGF23, Klotho, osteocalcin, osteopontin, calcitonin, pnp, procollagen III, OPG, RANKL, Sclerostin as well as other bone marker. Change in choice of assisted reproductive assistance technique as well as conceived pregnancies Change in spontaneous conception rate Change in live birth rate Change in number of spermatozoa expressing RANKL Change in semen pH, HCO3-, calcium, zink, phosphate, RANKL, RANK, OPG, FGF23, Klotho, osteocalcin, osteopontin. Difference in infection rate in the two groups
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Respectively 14 days, 80 days, 160 and 365 days after intervention |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial is describes as one year after inclusion of the last patient.
Last patient, last visit at site is 160 days after intervention, but we will contact all participants 1 year after inclusion, by telephone, to ask about conceived pregnancy, mode of conception and potential live births since conception was during intervention cf. secondary endpoints. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |