A Novel Aromatase Inhibitor, Leflutrozole, for Treatment of Non-Obstructive Azoospermia

NCT07571928 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2025-524774-42-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical interventional study aims to assess whether treatment with with leflutrozole can improve sperm production in infertile men with non-obstructive azoospermia selected by serum anti-mullerian hormone (AMH) or Inhibin B as a positive predictive biomarker.

Conditions

Infertility Due to Azoospermia; Infertility, Male

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with spermatozoa in the ejaculate at Week 12-20.

  The primary endpoint is proportion of patients with spermatozoa in the ejaculate at Week 20 (end-of-treatment).

  From enrollment to Week 20 (end-of-treatment)

Secondary Outcomes (20)

• Change in serum reproductive hormones

  Change from baseline to week 20 (end-of-treatment)

• Change in seminal fluid reproductive biomarkers

  Change from baseline to week 20 (end-of-treatment)

• Change in reproductive hormone ratios

  Change from baseline to week 20 (end-of-treatment)

• Change in body mass index

  Change from baseline to week 20 (end-of-treatment)

• Change in glycemic and insulin resistance markers

  Change from baseline to week 20 (end-of-treatment)

Study Arms (1)

Leflutrozole

EXPERIMENTAL

once-weekly oral Leflutrozole capsule 0.3 mg

Drug: Leflutrozole, Dose 2

Interventions

Leflutrozole, Dose 2 DRUG

Leflutrozole capsule 0.3 mg once weekly administered orally

Leflutrozole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent by participant
• Signed informed consent by participant's partner (must just be obtained before the par-ticipant starts treatment at Visit 1), if applicable, regarding blood samples, data collec-tion about fertility treatment as well as pregnancy and pregnancy outcome
• years
• 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).
• Serum AMH or Inhibin B level above the lower limit of quantification (LLOQ) at screening or within 6 months prior to screening
• Testosterone \< 15 nmol/L at screening or within 6 months prior to screening
• Serum estradiol above the lower limit of normal range (48 pmol/L) at screening or within 6 months prior to screening

You may not qualify if:

• Klinefelter or other major genetic conditions including large deletions on sex chromosomes
• Average testis size \> 20 mL unless obstruction has been excluded
• TESE procedure \< ½ year ago
• LH concentration \> 15 IU/L at screening
• Current abuse of steroids
• BMI \> 45 kg/m2
• Severe chronic diseases requiring daily medication
• Prior thromboembolic event within the last 24 months
• Cardiovascular event within the last 6 months judged as significant by the investigator
• Osteoporosis requiring medical treatment
• 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:
• Herbal products and non-routine vitamins
• Insulin
• Medication such as systemic corticosteroids, tricyclic antidepressants, and atypical antipsychotics
• Surgery scheduled for the trial duration period, except for minor, non-gastrointestinal surgical procedures at the discretion of the investigator

Sponsors & Collaborators

• ReproNovo SA: collaborator
• Martin Blomberg Jensen: lead

Study Sites (1)

Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital Herlev., Herlev,

Herlev, 2100, Denmark

Location

Related Publications (9)

• Pundir J, Achilli C, Bhide P, Sabatini L, Legro RS, Rombauts L, Teede H, Coomarasamy A, Zamora J, Thangaratinam S. Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis. Hum Reprod Update. 2021 Apr 21;27(3):474-485. doi: 10.1093/humupd/dmaa055.

  PMID: 33374012 BACKGROUND

• Wickramasinghe LC, Tsantikos E, Kindt A, Raftery AL, Gottschalk TA, Borger JG, Malhotra A, Anderson GP, van Wijngaarden P, Hilgendorff A, Hibbs ML. Granulocyte Colony-Stimulating Factor is a Determinant of Severe Bronchopulmonary Dysplasia and Coincident Retinopathy. Am J Pathol. 2023 Dec;193(12):2001-2016. doi: 10.1016/j.ajpath.2023.07.006. Epub 2023 Sep 9.

  PMID: 37673326 BACKGROUND

• Yang Y, Chen S, Chen H, Guo Y, Teng X. The efficacy of anastrozole in subfertile men with and without abnormal testosterone to estradiol ratios. Transl Androl Urol. 2022 Sep;11(9):1262-1270. doi: 10.21037/tau-22-95.

  PMID: 36217397 BACKGROUND

• Cavallini G, Beretta G, Biagiotti G. Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH. Asian J Androl. 2011 Nov;13(6):895-7. doi: 10.1038/aja.2011.44. Epub 2011 Jun 27.

  PMID: 21706040 BACKGROUND

• Helo S, Ellen J, Mechlin C, Feustel P, Grossman M, Ditkoff E, McCullough A. A Randomized Prospective Double-Blind Comparison Trial of Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal Infertile Men. J Sex Med. 2015 Aug;12(8):1761-9. doi: 10.1111/jsm.12944. Epub 2015 Jul 14.

  PMID: 26176805 BACKGROUND

• Eisenberg ML, Lathi RB, Baker VL, Westphal LM, Milki AA, Nangia AK. Frequency of the male infertility evaluation: data from the national survey of family growth. J Urol. 2013 Mar;189(3):1030-4. doi: 10.1016/j.juro.2012.08.239. Epub 2012 Sep 23.

  PMID: 23009868 BACKGROUND

• Schlegel PN, Sigman M, Collura B, De Jonge CJ, Eisenberg ML, Lamb DJ, Mulhall JP, Niederberger C, Sandlow JI, Sokol RZ, Spandorfer SD, Tanrikut C, Treadwell JR, Oristaglio JT, Zini A. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. Fertil Steril. 2021 Jan;115(1):62-69. doi: 10.1016/j.fertnstert.2020.11.016. Epub 2020 Dec 9.

  PMID: 33309061 BACKGROUND

• Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015 Apr 26;13:37. doi: 10.1186/s12958-015-0032-1.

  PMID: 25928197 BACKGROUND

• Thonneau P, Marchand S, Tallec A, Ferial ML, Ducot B, Lansac J, Lopes P, Tabaste JM, Spira A. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod. 1991 Jul;6(6):811-6. doi: 10.1093/oxfordjournals.humrep.a137433.

  PMID: 1757519 BACKGROUND

MeSH Terms

Conditions

Infertility, Male

Interventions

leflutrozole

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Study Officials

• Martin Blomberg Jensen, D.M.Sc.

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mads Joon Jorsal, MD

CONTACT

+45 38686364; mads.joon.jorsal@regionh.dk

Emil Brink Wriedt, MD

CONTACT

+45 38686364; emil.brink.wriedt@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Research Department Endocrinology

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: May 6, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)