E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male infertility especially low sperm count |
mandlig infertilitet |
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E.1.1.1 | Medical condition in easily understood language |
poor semen quality |
nedsat sædkvalitet |
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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 | 18.0 |
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 |
to investigate whteher short term Denosumab treatment can imporve sperm count and male fertility |
• Ændring i sædcelleproduktion (spermatozo-antal, -koncentration) |
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E.2.2 | Secondary objectives of the trial |
change in semen quality change in Inhibin B change in sexhormones or gonadotropins change in BMD Change in vitamin d metabolites change in endocrine bone factors change in ART change in sperm positive for CYP24A1 Change in DFI change in concentraion of bone markers in spermaplasma
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• Ændring i sædkvalitet (spermatozo-antal, -koncentration, -motilitet, -morfologi og sædvolumen) • Ændring i serum Inhibin-B konc. • Ændring i serumniveau af kønshormoner (FSH, LH, AMH, testosteron, østradiol og SHBG) • Ændring i bone mineral density vurderet ved DXA. • Ændring i serumniveau af inaktivt D vitamin, 1,25(OH)2D3, 25-OHD3, 24,25(OH)2D3, PTH, basisk phosphatase, ioniseret calcium phosphat, FGF23, Klotho, osteocalcin, osteopontin, calcitonin, pnp, procollagen III, OPG, RANKL, Sclerostin samt andre knoglemarkører. • Ændring eller forskel af metode ved assisteret reproduktion samt andel af opnåede graviditeter • Ændring i spontan konceptionsrate. • Ændring i antallet af procentdelen af sædceller der udtrykker CYP24A1 ved annulus • Ændringer i DFI (DNA fragmentering) eller i sædvæske af pH, bikarbonat, calcium, zink, phosphat, RANKL, RANK, OPG, FGF23, Klotho, osteocalcin, osteopontin.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
men > 18 years with male infertility sperm concentration > 0.100 million/ml |
Mænd > 18 år, der henvises til udredning for mandlig infertilitet med sædcellekoncentration > 0,100 mio./ml. Mændene skal enten have sædcellekoncentration <20 mio./ml eller <50 % progressivt motile spermatozoer (A) eller <12 % morfologisk normale spermatozoer (strict criteria)
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E.4 | Principal exclusion criteria |
men with chronical illness and serious co-morbidities in need of treatment |
Mænd med kroniske sygdomme (diabetes mellitus, stofskifte lidelser, behandlingskrævende hormonelle lidelser, maligne sygdomme eller kendte sygdomme, der kan påvirkes af eller interferere med indtag vitamin D ekskluderes (granulomatøse sygdomme som sarkoidose, tuberkulose, wegeners, vasculitsygdomme samt tarmsygdomme som morbus chron eller collitis ulcerosa etc). |
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E.5 End points |
E.5.1 | Primary end point(s) |
change in the number of total sperm and sperm concentration |
sædkoncentration og total nummer af sæd |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 5 days, 2 weeks, 6 weeks, and then monthly until 6 months after inclusion. |
efter 5, 19 dage og herefter en gang om måneden indtil 6 måneder efter inklusionen |
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E.5.2 | Secondary end point(s) |
change in semen quality change in Inhibin B change in sexhormones or gonadotropins change in BMD Change in vitamin d metabolites change in endocrine bone factors change in ART |
• Ændring i sædkvalitet (spermatozo-antal, -koncentration, -motilitet, -morfologi og sædvolumen) • Ændring i serum Inhibin-B konc. • Ændring i serumniveau af kønshormoner (FSH, LH, AMH, testosteron, østradiol og SHBG) • Ændring i bone mineral density vurderet ved DXA. • Ændring i serumniveau af inaktivt D vitamin, 1,25(OH)2D3, 25-OHD3, 24,25(OH)2D3, PTH, basisk phosphatase, ioniseret calcium phosphat, FGF23, Klotho, osteocalcin, osteopontin, calcitonin, pnp, procollagen III, OPG, RANKL, Sclerostin samt andre knoglemarkører. • Ændring eller forskel af metode ved assisteret reproduktion samt andel af opnåede graviditeter • Ændring i spontan konceptionsrate. • Ændring i antallet af procentdelen af sædceller der udtrykker CYP24A1 ved annulus • Ændringer i DFI (DNA fragmentering) eller i sædvæske af pH, bikarbonat, calcium, zink, phosphat, RANKL, RANK, OPG, FGF23, Klotho, osteocalcin, osteopontin.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 5 days, 2 weeks, 6 weeks, and then monthly until 6 months after inclusion. |
efter 5, 19 dage og herefter en gang om måneden indtil 6 måneder efter inklusionen |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
New indication for denosumab |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |