The NOVA-NOA Trial A Novel Aromatase Inhibitor, Leflutrozole, for Treatment of Non-Obstructive Azoospermia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Herlev Hospital

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Decision date (initial)

2026-04-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

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 the aromatase inhibitor, Leflutrozole, 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 7

1. Signed informed consent by participant
2. Signed informed consent by participant’s partner (must just be obtained before the participant starts treatment at Visit 1), if applicable, regarding blood samples, data col-lection about fertility treatment as well as pregnancy and pregnancy outcome
3. 18-55 years
4. Azoospermia verified by at least 2 semen samples, average semen volume >= 1,0 ml with no identifiable sign of obstruction (samples taken at Visit -1 and at Visit 0 prior to confirmation of eligibility and dosing).
5. Serum AMH or Inhibin B level above the lower limit of quantification (LLOQ) at screening or within 6 months prior to screening
6. Testosterone < 15 nmol/L at screening or within 6 months prior to screening
7. Serum estradiol above the lower limit of normal range (48 pmol/L) at screening or within 6 months prior to screening

Exclusion criteria 16

1. Klinefelter or other major genetic conditions including large deletions on sex chromo-somes
2. Average testis size > 20 mL unless obstruction has been excluded
3. TESE procedure < ½ year ago
4. LH concentration > 15 IU/L at screening
5. Current abuse of steroids
6. BMI > 45 kg/m2
7. Severe chronic diseases requiring daily medication
8. Prior thromboembolic event within the last 24 months
9. Cardiovascular event within the last 6 months judged as significant by the investigator
10. Osteoporosis requiring medical treatment
11. Use of any prescription or non-prescription medication (apart from routine vitamins, occasional use of paracetamol, acetylsalicylic acid, or ibuprofen) which could interfere with pharmacokinetic or pharmacodynamic results, as judged by the investigator, such as: o Herbal products and non-routine vitamins o Insulin o Medication such as systemic corticosteroids, tricyclic antidepressants, and atypical antipsychotics
12. Surgery scheduled for the trial duration period, except for minor, non-gastrointestinal surgical procedures at the discretion of the investigator
13. Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer), which in the investigator’s opinion could interfere with the results of the trial
14. Serum prostate specific antigen (PSA) > 3 ng/mL at screening or within 6 months prior to screening
15. Hematocrit >50% at screening or within 6 months prior to screening
16. Mental incapacity, language barriers or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or co-operation during the trial, as judged by the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is proportion of patients with spermatozoa in the ejaculate at Week 12-20.

Secondary endpoints 16

1. Changes in serum reproductive hormones (FSH, LH, Testosterone, Estradiol, Inhibin B, AMH, SHBG)
2. Changes in the concentration of RANKL, OPG, AMH, and Inhibin B in seminal fluid
3. Change in serum Inhibin B/FSH ratio, Testosterone/LH ratio, Testosterone/Estradiol and AMH/Testosterone ratio
4. Changes in BMI
5. Changes in HbA1c, fasting- glucose, c-peptide, insulin and HOMA-IR
6. Changes in lipids (total cholesterol, LDL, HDL and triglycerides)
7. Changes in hematocrit
8. Change in circulating markers of bone resorption and formation (PINP and CTX)
9. Change in mineral homeostasis in spot urine (albumin, calcium, magnesium, iron, fer-ritin, phosphate, zinc, bicarbonate, citrate)
10. Change in mineral homeostasis in serum (albumin, calcium, phosphate, magnesium, iron, ferritin, transferrin, hepcidin, zinc)
11. Change in mineral homeostasis in seminal fluid (albumin, calcium, phosphate, magne-sium, iron, ferritin, zinc)
12. Changes in calciotropic hormones (PTH, Klotho and FGF23)
13. Changes in serum vitamin D metabolites (cholecalciferol, 25OHD, 24,25OHD, 1,25OH2D3 and cholecalciferol/25OHD ratio, 25OHD/24,25OHD ratio)
14. Changes in androstenedione, cortisone and DHEAS
15. Plasma and semen concentrations of leflutrozole in the participant and plasma concen-trations of leflutrozole in the female partner
16. Change in sperm count, concentration, motility, and morphology when possible.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Herlev Hospital

Sponsor organisation

Herlev Hospital

Address

Borgmester Ib Juuls Vej 1

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Herlev Hospital

Contact name

Martin Blomberg Jensen

Public contact point

Organisation

Herlev Hospital

Contact name

Martin Blomberg Jensen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications