Clinical trial NCT06993155: A Clinical Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function in Men With Hypogonadotropic Hypogonadism
Official title: A Randomized, Placebo-controlled, Double-blind, Parallel-group, Dose Response Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function in Men With Hypogonadotropic Hypogonadism
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hypogonadotropic Hypogonadism
Lead sponsor: ReproNovo SA
Sponsor class: INDUSTRY
First posted: 2025-05-28
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate three doses of the drug leflutrozole on improvement of semen quality in men with hypogonadotropic hypogonadism, a condition that affects hormone levels and fertility. It will also study the safety of leflutrozole.

The main questions it aims to answer are:

* Does leflutrozole improve semen quality?
* What medical problems do participants experience when taking leflutrozole?

Researchers will compare leflutrozole to a placebo (a look-alike substance that contains no drug).

Participants will:

* Take leflutrozole or a placebo orally once a week for 16 weeks.
* Visit the clinic every 4 weeks for checkups and tests.
* Provide semen samples to measure changes in semen quality.
* Have their blood tested to measure hormone levels and ensure safety.
* Be monitored for any side effects.


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 Sex Hormone Binding Globulin within or above normal range at screening.
* 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.

Primary outcomes:
measure: Change in total motile sperm count (TMSC) after 16 weeks of treatment.
timeFrame: From baseline to the end of treatment at 16 weeks.
Secondary outcomes:
measure: Changes in total sperm count (TSC), sperm concentration, sperm motility, normal sperm morphology, and semen volume after 16 weeks of treatment.
timeFrame: From baseline to the end of treatment at 16 weeks.
measure: Percentage of participants with TMSC ≥5 million, ≥10 million, and ≥20 million after 16 weeks of treatment.
timeFrame: At end of treatment at 16 weeks.
measure: Percentage of participants with a relative increase of ≥50%, ≥75% and ≥100% in TMSC after 16 weeks of treatment.
timeFrame: From baseline to the end of treatment at 16 weeks.
measure: Percentage of participants with sperm DNA fragmentation index (DFI) <15%, <25% and <30% after 16 weeks of treatment.
timeFrame: At end of treatment at 16 weeks.
measure: Normalization of serum total testosterone levels in ≥75% of participants after 16 weeks of treatment.
timeFrame: At end of treatment at 16 weeks.
measure: Percentage of participants with normal serum total testosterone levels after 4, 8, 12 and 16 weeks of treatment.
timeFrame: At 4 , 8, 12 and 16 weeks of treatment.
measure: Changes in serum concentrations of total testosterone, free testosterone, bioavailable testosterone, SHBG, FSH, LH, estradiol, inhibin B, and total testosterone / estradiol ratio after 4, 8, 12 and 16 weeks of treatment.
timeFrame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
measure: Plasma concentrations of leflutrozole after 4, 8, 12 and 16 weeks of treatment.
timeFrame: At 4 , 8, 12 and 16 weeks of treatment.
measure: Semen concentrations of leflutrozole after 12 weeks of treatment.
timeFrame: After 12 weeks of treatment.
measure: Changes in libido based upon questionnaire after 4 and 16 weeks of treatment.
timeFrame: From baseline to 4 and 16 weeks of treatment.
measure: Changes in energy based upon questionnaire after 4 and 16 weeks of treatment.
timeFrame: From baseline to 4 and 16 weeks of treatment.
measure: Percentage of participants who overshoot testosterone at any time during the trial.
timeFrame: At any time during the trial
measure: Frequency and intensity of adverse events, including serious adverse events and adverse events leading to discontinuation.
timeFrame: From informed consent to end of trial
measure: Changes in circulating levels of clinical chemistry and hematology parameters after 4, 8, 12 and 16 weeks of treatment.
timeFrame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
measure: Changes in serum prostate-specific antigen (PSA) levels after 4, 8, 12 and 16 weeks of treatment.
timeFrame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
measure: Changes in ECG parameters after 16 weeks of treatment.
timeFrame: From baseline to the end of treatment at 16 weeks.
measure: Changes in systolic and diastolic arterial blood pressure, and proportion of participants with systolic blood pressure >140 mmHg and diastolic pressure >90 mmHg, and proportion of participants with systolic blood pressure >160 mmHg and diastolic pressure
timeFrame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
measure: Changes in lipids and in carbohydrate metabolism parameters after 16 weeks of treatment
timeFrame: From baseline to the end of treatment at 16 weeks.
measure: Changes in serum C-terminal cross-linking telopeptide of type 1 collagen (s-CTx) and serum procollagen type 1 N propeptide (s PINP) after 16 weeks of treatment.
timeFrame: From baseline to the end of treatment at 16 weeks.
Other outcomes:
Locations:
Study officials:
affiliation: ReproNovo Aps
name: Medical Director
role: STUDY_DIRECTOR
References: