Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
16
Countries
1
Sites
1
Male infertility
The aim of this intervention is to investigate whether Denosumab can improve semen quality in a subgroup of infertile men.
Key facts
- Sponsor
- Region Hovedstaden
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Male Urogenital Diseases [C12]
- Trial duration
- 30 Apr 2025 → 21 Apr 2026
- Decision date (initial)
- 2024-06-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The aim of this intervention is to investigate whether Denosumab can improve semen quality in a subgroup of infertile men.
Conditions and MedDRA coding
Male infertility
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Infertile men > 18 years and < 60 years with azoospermia with normal semen volume verified with a minimum of 2 semen samples
- Testicle size (Prader orchidometer) ≤ 15 ml on both sides
- No identified causes of obstruction
- Serum AMH ≥ 18 pmol/L
Exclusion criteria 16
- Men with chronic diseases (diabetes mellitus, thyroid disease, endocrine diseases requirering treatment such as sarcoidosis, tuberculosis, wegeners, vasculitis as well as inflammatory bowel diseases e.g. chron's disease or ulcerative colitis etc).
- Poor dental status og dental implants
- Latex allergy
- Serum Inhibin B < 15 pg/mL
- Androgen replacement therapy
- Hypogonadotropic hypogonadism
- BMI ≥ 35 kg/m2
- Chromosome abnormalities eg. Klinefelter Syndrome, XX male
- AZFa/b/c microdeletions except b2/b3 og gr/gr
- Verified/identified CFTR mutation
- Men with active or previous malignant disease
- Men in treatment for osteoporosis
- Total calcium < 2.14 mmol/L or Albumin corrected calcium <2.17 mmol/L
- Serum 25OHD < 25 nmol/L
- eGFR <60 mL/min/1.73m^2
- Prior thromboembolic event
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Identification of sperm in either semen sample or TESE at day 90 that ideally is compared with prior TESE, if such is available from before study participation
Secondary endpoints 7
- Change in proliferation or apoptosis of germ cells assessed by KI-67, PCNA, cleaved parp expression or TUNEL assay on tissue from TESE at day 90 that is subsequently compared with prior TESE if such is available
- Number of participants with sperm in the ejaculate (sperm concentration million/mL) assessed by semen sample delivered at day 14 or day 80
- Number of pregnancies achieved by sperm from the ejaculate or from TESE
- Change in serum levels of reproductive hormones (FSH, LH, AMH, Inhibin B, INSL3) at day 14 and day 80
- Change in seminal fluid levels of reproductive hormones (AMH, Inhibin B, INSL3) at day 14 and day 80
- Change in serum levels of sex hormones (testosterone, estradiol, SHBG) at day 14 and day 80
- Change in the endocrine gonadal function (Inhibin B/FSH ratio, testosterone/LH ratio og AMH/testosterone ratio) at day 14 and day 80
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Prolia 60 mg solution for injection in pre-filled syringe
PRD3618671 · Product
- Active substance
- Denosumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 60 mg/ml milligram(s)/millilitre
- Max total dose
- 60 mg/l milligram(s)/litre
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M05BX04 — -
- Marketing authorisation
- EU/1/10/618/003
- MA holder
- AMGEN EUROPE B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Femar, filmovertrukne tabletter
PRD643708 · Product
- Active substance
- Letrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2.5 mg milligram(s)
- Max total dose
- 2.5 mg milligram(s)
- Max treatment duration
- 120 Day(s)
- Authorisation status
- Authorised
- ATC code
- L02BG04 — LETROZOLE
- Marketing authorisation
- 18420
- MA holder
- NOVARTIS HEALTHCARE A/S
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Hovedstaden
- Sponsor organisation
- Region Hovedstaden
- Address
- Borgmester Ib Juuls Vej 1
- City
- Herlev
- Postcode
- 2730
- Country
- Denmark
Scientific contact point
- Organisation
- Region Hovedstaden
- Contact name
- Martin Blomberg Jensen
Public contact point
- Organisation
- Region Hovedstaden
- Contact name
- Mads Joon Jorsal
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ended | 16 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2025-04-30 | 2025-04-30 | 2025-10-14 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 16 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Azoospermi protokol_CTIS_Clean | 3 |
| Protocol (for publication) | Azoospermi protokol_CTIS_Track Changes | 3 |
| Protocol (for publication) | Azoospermi protokol_Revised_CLEAN | 4 |
| Protocol (for publication) | Azoospermi protokol_Revised_track_changes | 4 |
| Protocol (for publication) | dag 180 sprgeskema | 1 |
| Protocol (for publication) | dag 80 sprgeskema | 1 |
| Recruitment arrangements (for publication) | Recruitment and Informed consent procedure_track changes | 1 |
| Recruitment arrangements (for publication) | recruitment and informed consent_NT_NOA | 3 |
| Subject information and informed consent form (for publication) | Deltagerinformation_NT_NOA | 3 |
| Subject information and informed consent form (for publication) | Deltagerinformation_NT_NOA_REVISED_CLEAN | 5 |
| Subject information and informed consent form (for publication) | Deltagerinformation_NT_NOA_REVISED_track_changes | 5 |
| Subject information and informed consent form (for publication) | Deltagerinformation_NT_NOA_Track_changes_V2 | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring NT NOA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Femar filmovertrukne tabletter mg produktresume | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Produktresme_prolia | 1 |
| Synopsis of the protocol (for publication) | Synopsis | 1 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-20 | Denmark | Acceptable 2024-05-31
|
2024-06-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-02-10 | Denmark | Acceptable 2025-03-13
|
2025-03-14 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-04-10 | Acceptable 2025-03-13
|
||
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-04-10 | Denmark | 2025-04-10 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-08-19 | Denmark | 2025-08-19 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2026-03-30 | Denmark | 2026-03-30 |