A Phase 1/2 interventional study of Leflutrozole, Dose 2 in Infertility Due to Azoospermia and Infertility, Male, sponsored by Martin Blomberg Jensen. Active, not recruiting at 1 site in Denmark. Open to male participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Martin Blomberg Jensen · Phase 1/2, Interventional, and Treatment
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.
Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility and reflects a profound impairment of spermatogenesis. Men with NOA typically require surgical sperm retrieval procedures, such as testicular sperm aspiration (TESA), testicular sperm extraction (TESE), or micro-TESE, followed by intracytoplasmic sperm injection (ICSI). Even with surgical retrieval, sperm recovery rates remain limited and live birth rates are modest. At present, no pharmacological treatments are approved for male infertility, underscoring a substantial unmet clinical need.
Aromatase inhibitors reduce the conversion of testosterone to estradiol by inhibiting the CYP19A1 enzyme, thereby increasing the testosterone-to-estradiol ratio and stimulating gonadotropin secretion. Letrozole and anastrozole have been used off-label in infertile men, including selected patients with NOA, with small studies demonstrating that aromatase inhibition may induce the appearance of spermatozoa in the ejaculate. Leflutrozole is a novel, non-steroidal aromatase inhibitor and a derivative of letrozole with an extended half-life, allowing once-weekly oral dosing at substantially lower doses than conventional daily aromatase inhibitor regimens. Previous clinical studies in men with obesity-associated functional hypogonadism have demonstrated that once-weekly leflutrozole improves serum testosterone concentrations and semen parameters with an acceptable safety profile.
The NOVA-NOA trial is a single-center, prospective, interventional study designed to evaluate the efficacy and safety of leflutrozole in men with non-obstructive azoospermia. The study investigates whether 20 weeks of treatment with oral leflutrozole 0.3 mg administered once weekly can induce the presence of spermatozoa in the ejaculate and thereby potentially reduce the need for surgical sperm retrieval.
Following informed consent and confirmation of azoospermia at screening and baseline, eligible participants receive oral leflutrozole 0.3 mg once weekly for a total treatment duration of 20 weeks. Semen samples are collected prior to treatment and during therapy at predefined visits (Weeks 12, 16, and 20) to evaluate spermatogenic response. If spermatozoa are identified in any semen sample during treatment, participants are offered repeat semen sampling and referral to a fertility clinic for cryopreservation according to standard clinical practice. Participants continue study treatment until Week 20 irrespective of early detection of spermatozoa.
Blood and urine samples are collected longitudinally to characterize changes in reproductive hormones, metabolic parameters, mineral homeostasis, bone turnover markers, and circulating concentrations of leflutrozole. Seminal fluid is additionally analyzed for leflutrozole concentrations when sufficient ejaculate volume permits. These assessments are intended to describe the endocrine and systemic effects of sustained aromatase inhibition in men with NOA and to support mechanistic interpretation of any spermatogenic response.
Safety is evaluated throughout the study using repeated clinical assessments, laboratory monitoring, and systematic recording of adverse events. Key safety measures include monitoring of hematocrit, hemoglobin, prostate-specific antigen, liver biochemistry, and cardiovascular parameters. Participants are followed until Week 24 for on-site safety assessments, corresponding to more than five half-lives of the investigational medicinal product, and complete an additional safety and pregnancy outcome follow-up by telephone at Week 36.
Statistical analyses are conducted on an intention-to-treat basis. The primary efficacy analysis evaluates whether treatment with leflutrozole induces the presence of spermatozoa in the ejaculate, using an exact binomial testing framework under the assumption that untreated men with NOA would not spontaneously develop spermatozoa during the observation period. Secondary analyses describe within-participant changes in hormonal, metabolic, and exploratory semen parameters over time.
The overall objective of the NOVA-NOA trial is to determine whether, once-weekly leflutrozole administered without concomitant medication can induce spermatogenesis sufficient for the appearance of spermatozoa in the ejaculate of men with non-obstructive azoospermia, thereby offering a potential non-surgical pathway to biological fatherhood for a subset of this patient population.
282 studies on the registry are indexed under Infertility, Male; 65 are open to participants now.
This study's planned enrollment of 15 is below the median of 80 across 187 interventional studies indexed under Infertility, Male.
Browse Infertility, Male studies →Martin Blomberg Jensen is the lead sponsor of 13 studies on the registry; 4 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
once-weekly oral Leflutrozole capsule 0.3 mg
Drug: Leflutrozole, Dose 2
Leflutrozole capsule 0.3 mg once weekly administered orally
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).
Time frame: From enrollment to Week 20 (end-of-treatment)
Change in serum reproductive hormones
Change in serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, estradiol, inhibin B, anti-Müllerian hormone (AMH), and sex hormone-binding globulin (SHBG).
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in seminal fluid reproductive biomarkers
Change in concentrations of RANK ligand (RANKL), osteoprotegerin (OPG), anti-Müllerian hormone (AMH), and inhibin B measured in seminal
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in reproductive hormone ratios
Change in serum inhibin B/FSH ratio, testosterone/LH ratio, testosterone/estradiol ratio, and AMH/testosterone ratio.
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in body mass index
Change in body mass index (BMI) weight and height will be combined to calculate BMI in kg/m\^2
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in glycemic and insulin resistance markers
Change in HbA1c, fasting plasma glucose, fasting insulin, C-peptide, and homeostatic model assessment for insulin resistance (HOMA-IR)
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in lipid profile
Change in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in hematocrit
Change in hematocrit measured as a safety-related secondary outcome
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in markers of bone turnover
Change in serum procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX).
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in urinary mineral homeostasis
Change in spot urine concentrations of albumin, calcium, magnesium, iron, ferritin, phosphate, zinc, bicarbonate, and citrate.
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in serum mineral homeostasis
Change in serum concentrations of albumin, calcium, phosphate, magnesium, iron, ferritin, transferrin, hepcidin, and zinc
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in seminal fluid mineral concentrations
Change in seminal fluid concentrations of albumin, calcium, phosphate, magnesium, iron, ferritin, and zinc
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in calciotropic hormones
Change in serum parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and α-Klotho.
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in vitamin D metabolites
Change in serum concentrations of cholecalciferol, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, and derived vitamin D metabolite ratios
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in adrenal and androgen precursor hormones
Change in serum concentrations of androstenedione, cortisone, and dehydroepiandrosterone sulfate (DHEAS).
Time frame: Change from baseline to week 20 (end-of-treatment)
Leflutrozole concentrations in serum in participants
Plasma concentration of Leflutrozole in participants
Time frame: From enrollment to the end of trial at 24 weeks
Leflutrozole concentration in seminal fluid
Leflutrozole concentration in seminal fluid
Time frame: From enrollment to the end-of-treatment at 20 weeks
Leflutrozole concentration in partners
Plasma Leflutrozole concentration in the female partner
Time frame: From enrollment to week 16 after inclusion
Change in sperm parameters when measurable
Change in sperm count, concentration, motility, and morphology in participants with detectable spermatozoa in the ejaculate.
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in height
Change in height (centimeters)
Time frame: Change from baseline to week 20 (end-of-treatment)
Change in weight
Change in weight (kilograms)
Time frame: Change from baseline to week 20 (end-of-treatment)
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Martin Blomberg Jensen