Leflutrozole to improve semen quality and testicular hormone function in men

A Randomized, Placebo-controlled, Double-blind, Parallel-group, Dose-response Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function

This study will test whether taking leflutrozole once a week for 16 weeks improves semen quality in men with low testosterone and low motile sperm counts compared with placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 49 Years
• Sex: Male
• Sponsor: ReproNovo SA (Industry-sponsored)
• Locations: 4 sites (North Hollywood, California and 3 other locations)
• Trial ID: NCT06993155 on ClinicalTrials.gov

What this trial studies

Eligible men are assigned to one of three weekly oral doses of leflutrozole or a matching placebo and treated for 16 weeks. Clinic visits occur every four weeks for safety checks, semen collection, and blood tests to measure hormone changes. The trial compares changes in semen quality and records adverse events across dose groups and placebo. Hormone measurements are used to characterize effects on testicular function.

Who should consider this trial

Good fit: Adult men aged 18–49 with low total testosterone on two occasions, low total motile sperm count in two samples, semen volume ≥1.0 mL, and the specified hormone ranges are the intended participants.

Not a fit: Men with anatomical testicular abnormalities, pituitary or hypothalamic disease, prostate disease, recent use (within six months) of drugs or supplements that affect sex hormones, or those outside the 18–49 age range are unlikely to benefit from this trial.

Why it matters

Potential benefit: If effective, leflutrozole could improve semen quality and potentially increase the chances of natural conception for men with low testosterone and low sperm motility.

How similar studies have performed: Other aromatase inhibitors have produced mixed but sometimes promising improvements in hormones and semen parameters in small studies, while leflutrozole itself is less well studied.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent form prior to any-related trial activity.
* Adult men aged 18-49 years (both inclusive).
* Low serum total testosterone concentration on two occasions.
* Serum estradiol (E2) level within or above normal range at screening.
* Serum Luteinizing Hormone level within or below normal range at screening.
* Low total motile sperm count in two samples.
* Semen volume ≥1.0 mL in two samples.
* Ability to understand and comply with the requirements of the protocol.

Exclusion Criteria:

* Anatomical abnormalities of the testes or malignant or benign tumors of the testes.
* Pituitary or hypothalamic disease.
* Prostate disease.
* Treatment with one or more of the following prescription drugs or over-the-counter medications or supplements for 6 months prior to the screening visit:

  1. Compounds with androgenic or estrogenic properties (i.e., agonist or antagonist) or that affect production of sex hormones.
  2. 5-α reductase inhibitors, e.g., finasteride and dutasteride.
  3. Fertility drugs, including clomiphene, FSH, hMG and hCG preparations.
  4. Growth hormone.
  5. Opioid-receptor antagonists, e.g., naloxone and long-acting opioids.
  6. Selective α-adrenergic-receptor antagonists (alpha blockers).
  7. Topical or systemic testosterone replacement therapy (TRT).
  8. Anabolic steroids.
* Inability to reliably produce the required semen samples for trial assessments due to significant erectile dysfunction, anorgasmia, or other reasons.
* Participation in any clinical trial using clinical intervention within 3 months before the screening visit or 5 half-lives of investigational product administration, whichever is shorter.
* Any clinically significant 12-lead ECG abnormalities at screening.
* Known history of thromboembolic disease.
* Grade 3 lower extremity edema.
* Known cardiovascular disease.
* Known history of osteoporosis or fragility fractures.
* Known moderate or severe impairment of renal or hepatic function.
* Untreated diagnosis of sleep apnea.
* History of cancer within the last 5 years.
* Known alcohol and/or drug abuse within the last 12 months prior to randomization or evidence of such abuse indicated by the laboratory results during the screening assessments.
* Known chronic opioid use and/or misuse within the last 12 months prior to randomization.
* Any psychiatric or medical disorder or circumstance, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol.
* Hypersensitivity to any active ingredients or excipients in the medicinal products used in this trial.

Where this trial is running

North Hollywood, California and 3 other locations

• ReproNovo Investigational Site — North Hollywood, California, United States (Recruiting)
• ReproNovo Investigational Site — Pomona, California, United States (Recruiting)
• ReproNovo Investigational Site — Garden City, New York, United States (Recruiting)
• ReproNovo Investigational Site — Middleburg Heights, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: Public Disclosure

Conditions Semen Quality