Semen QualityPhase 2ETNANCT06993155
A Clinical Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function
A Phase 2 study testing Leflutrozole, Dose 1, Leflutrozole, Dose 2 and Leflutrozole, Dose 3 in people with Semen Quality, run by ReproNovo Aps at 4 sites in United States.
Trial summary
The goal of this clinical trial is to evaluate three doses of the drug leflutrozole on improvement of semen quality in men. 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… Read more about this study
- Who is it for?
- Ages 18 to 49 years, men only
- Conditions the study is for
- Semen Quality
- What is being tested?
- Leflutrozole, Dose 1, Leflutrozole, Dose 2 and Leflutrozole, Dose 3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 4 sitesUnited States
- Study dates
- 27 Jun 2025to Nov 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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:
- Compounds with androgenic or estrogenic properties (i.e., agonist or antagonist) or that affect production of sex hormones.
- 5-α reductase inhibitors, e.g., finasteride and dutasteride.
Show all 26Show fewer
- Fertility drugs, including clomiphene, FSH, hMG and hCG preparations.
- Growth hormone.
- Opioid-receptor antagonists, e.g., naloxone and long-acting opioids.
- Selective α-adrenergic-receptor antagonists (alpha blockers).
- Topical or systemic testosterone replacement therapy (TRT).
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
ReproNovo Investigational Site
Garden City, New York, 11530
ReproNovo Investigational Site, +45 32225466, publicdisclosure@repronovo.com
- Recruiting
ReproNovo Investigational Site
Middleburg Heights, Ohio, 44130
ReproNovo Investigational Site, +45 32225466, publicdisclosure@repronovo.com
- Recruiting
ReproNovo Investigational Site
North Hollywood, California, 91606
ReproNovo Investigational Site, +45 32225466, publicdisclosure@repronovo.com
- Recruiting
ReproNovo Investigational Site
Pomona, California, 91767
ReproNovo Investigational Site, +45 32225466, publicdisclosure@repronovo.com
About this study
Official title: A Randomized, Placebo-controlled, Double-blind, Parallel-group, Dose-response Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function
The goal of this clinical trial is to evaluate three doses of the drug leflutrozole on improvement of semen quality in men. It will also study the safety of leflutrozole.
The main questions it aims to answer are:
Read more
- 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.
- Conditions
- Semen Quality
- Being tested
- Leflutrozole, Dose 1, Leflutrozole, Dose 2, Leflutrozole, Dose 3, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leflutrozole, Dose 1Drug
Leflutrozole, Dose 1 once weekly for 16 weeks
Leflutrozole, Dose 2Drug
Leflutrozole, Dose 2 once weekly for 16 weeks
Leflutrozole, Dose 3Drug
Leflutrozole, Dose 3 once weekly for 16 weeks
PlaceboDrug
Placebo once weekly for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Leflutrozole, 0.05 mg | Experimental | Leflutrozole, 0.05 mg, oral capsule, once weekly for 16 weeks Receives: Drug: Leflutrozole, Dose 1 |
| Leflutrozole, 0.1 mg | Experimental | Leflutrozole, 0.1 mg, oral capsule, once weekly for 16 weeks Receives: Drug: Leflutrozole, Dose 2 |
| Leflutrozole, 0.3 mg | Experimental | Leflutrozole, 0.3 mg, oral capsule, once weekly for 16 weeks Receives: Drug: Leflutrozole, Dose 3 |
| Placebo | Placebo comparator | Placebo, oral capsule, once weekly for 16 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total motile sperm count (TMSC) after 16 weeks of treatment.
Total motile sperm count will be assessed through semen analysis conducted at specialized andrology laboratories.
Measured: From baseline to the end of treatment at 16 weeks.
Secondary outcomes (21)
Changes in total sperm count (TSC), sperm concentration, sperm motility, normal sperm morphology, and semen volume after 16 weeks of treatment.
Sperm parameters will be assessed through semen analysis conducted at specialized andrology laboratories.
Measured: From baseline to the end of treatment at 16 weeks.
Percentage of participants with TMSC ≥5 million, ≥10 million, and ≥20 million after 16 weeks of treatment.
Total motile sperm count will be assessed through semen analysis conducted at specialized andrology laboratories.
Measured: At end of treatment at 16 weeks.
Percentage of participants with a relative increase of ≥50%, ≥75% and ≥100% in TMSC after 16 weeks of treatment.
Total motile sperm count will be assessed through semen analysis conducted at specialized andrology laboratories.
Measured: From baseline to the end of treatment at 16 weeks.
Percentage of participants with sperm DNA fragmentation index (DFI) <15%, <25% and <30% after 16 weeks of treatment.
DNA fragmentation index will be analyzed at a specialized andrology laboratory.
Measured: At end of treatment at 16 weeks.
Percentage of participants with serum total testosterone levels within the range of 450-1000 ng/dL after 4, 8, 12 and 16 weeks of treatment.
Blood samples will be analyzed at a central laboratory.
Measured: At 4 , 8, 12 and 16 weeks of treatment.
Percentage of participants with serum total testosterone levels within the normal range of 300-1000 ng/dL after 4, 8, 12 and 16 weeks of treatment (for participants with baseline levels <300 ng/dL).
Blood samples will be analyzed at a central laboratory.
Measured: At 4 , 8, 12 and 16 weeks of treatment.
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.
Blood samples will be analyzed at a central laboratory.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Plasma concentrations of leflutrozole after 4, 8, 12 and 16 weeks of treatment.
Blood samples will be analyzed at a central laboratory.
Measured: At 4 , 8, 12 and 16 weeks of treatment.
Semen concentrations of leflutrozole after 12 weeks of treatment.
Semen analysis will be performed at a central laboratory.
Measured: After 12 weeks of treatment.
Changes in libido based upon questionnaire after 4 and 16 weeks of treatment.
Participants will complete the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q SF). The questions on libido use a 5-point scale, ranging from "never" (worst outcome) to "always" (best outcome).
Measured: From baseline to 4 and 16 weeks of treatment.
Changes in energy based upon questionnaire after 4 and 16 weeks of treatment.
Participants will complete the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q SF). The questions on energy use a 5-point scale, ranging from "not at all" (best outcome) to "extremely" (worst outcome).
Measured: From baseline to 4 and 16 weeks of treatment.
Percentage of participants who overshoot testosterone at any time during the trial.
Blood samples will be analyzed at a central laboratory
Measured: At any time during the trial
Frequency and intensity of adverse events, including serious adverse events and adverse events leading to discontinuation.
Adverse events will be collected from participant sign informed consent to end of trial
Measured: From informed consent to end of trial
Changes in circulating levels of clinical chemistry and hematology parameters after 4, 8, 12 and 16 weeks of treatment.
Blood samples will be analyzed at a central laboratory.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in serum prostate-specific antigen (PSA) levels after 4, 8, 12 and 16 weeks of treatment.
Blood samples will be analyzed at a central laboratory.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in ECG parameters after 16 weeks of treatment.
ECG will be measured at the trial sites and analyzed centrally.
Measured: From baseline to the end of treatment at 16 weeks.
Changes in systolic and diastolic arterial blood pressure
Blood pressure will be taken at the trial sites.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Proportion of participants with systolic blood pressure >140 mmHg and diastolic pressure >90 mmHg
Blood pressure will be taken at the trial sites.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Proportion of participants with systolic blood pressure >160 mmHg and diastolic pressure >110 mmHg
Blood pressure will be taken at the trial sites.
Measured: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in lipids and in carbohydrate metabolism parameters after 16 weeks of treatment
Blood samples will be analyzed at a central laboratory.
Measured: From baseline to the end of treatment at 16 weeks.
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.
Blood samples will be analyzed at a central laboratory.
Measured: From baseline to the end of treatment at 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2025
- Study start27 Jun 2025
- Primary completionJul 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Semen QualityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ReproNovo Aps
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, ReproNovo Aps
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06993155
- Sponsor's protocol ID
- RPN-LFT01
- Acronym
- ETNA
- Status last verified
- Feb 2026
- First submitted
- 19 May 2025
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind, Parallel-group, Dose-response Trial Evaluating the Efficacy and Safety of Leflutrozole on Testicular Function
- ClinicalTrials.gov ID
- NCT06993155
- Acronym / sponsor ID
- ETNA / RPN-LFT01
- Conditions
- Semen Quality
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- ReproNovo ApsIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2025 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 28 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate three doses of the drug leflutrozole on improvement of semen quality in men. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Leflutrozole, 0.05 mg | Experimental | Drug: Leflutrozole, Dose 1Leflutrozole, 0.05 mg, oral capsule, once weekly for 16 weeks |
| Leflutrozole, 0.1 mg | Experimental | Drug: Leflutrozole, Dose 2Leflutrozole, 0.1 mg, oral capsule, once weekly for 16 weeks |
| Leflutrozole, 0.3 mg | Experimental | Drug: Leflutrozole, Dose 3Leflutrozole, 0.3 mg, oral capsule, once weekly for 16 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, oral capsule, once weekly for 16 weeks |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (26 listed)
- 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:
- Inability to reliably produce the required semen samples for trial assessments due to significant erectile dysfunction, anorgasmia, or other reasons.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leflutrozole, Dose 1Leflutrozole, Dose 1 once weekly for 16 weeks | Drug | Leflutrozole, 0.05 mg |
| Leflutrozole, Dose 2Leflutrozole, Dose 2 once weekly for 16 weeks | Drug | Leflutrozole, 0.1 mg |
| Leflutrozole, Dose 3Leflutrozole, Dose 3 once weekly for 16 weeks | Drug | Leflutrozole, 0.3 mg |
| PlaceboPlacebo once weekly for 16 weeks | Drug | Placebo |
Primary outcome
Change in total motile sperm count (TMSC) after 16 weeks of treatment.
Time frame: From baseline to the end of treatment at 16 weeks.
Total motile sperm count will be assessed through semen analysis conducted at specialized andrology laboratories.
21 secondary outcomes
Changes in total sperm count (TSC), sperm concentration, sperm motility, normal sperm morphology, and semen volume after 16 weeks of treatment.
Time frame: From baseline to the end of treatment at 16 weeks.
Percentage of participants with TMSC ≥5 million, ≥10 million, and ≥20 million after 16 weeks of treatment.
Time frame: At end of treatment at 16 weeks.
Percentage of participants with a relative increase of ≥50%, ≥75% and ≥100% in TMSC after 16 weeks of treatment.
Time frame: From baseline to the end of treatment at 16 weeks.
Percentage of participants with sperm DNA fragmentation index (DFI) <15%, <25% and <30% after 16 weeks of treatment.
Time frame: At end of treatment at 16 weeks.
Percentage of participants with serum total testosterone levels within the range of 450-1000 ng/dL after 4, 8, 12 and 16 weeks of treatment.
Time frame: At 4 , 8, 12 and 16 weeks of treatment.
Percentage of participants with serum total testosterone levels within the normal range of 300-1000 ng/dL after 4, 8, 12 and 16 weeks of treatment (for participants with baseline levels <300 ng/dL).
Time frame: At 4 , 8, 12 and 16 weeks of treatment.
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.
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Plasma concentrations of leflutrozole after 4, 8, 12 and 16 weeks of treatment.
Time frame: At 4 , 8, 12 and 16 weeks of treatment.
Semen concentrations of leflutrozole after 12 weeks of treatment.
Time frame: After 12 weeks of treatment.
Changes in libido based upon questionnaire after 4 and 16 weeks of treatment.
Time frame: From baseline to 4 and 16 weeks of treatment.
Changes in energy based upon questionnaire after 4 and 16 weeks of treatment.
Time frame: From baseline to 4 and 16 weeks of treatment.
Percentage of participants who overshoot testosterone at any time during the trial.
Time frame: At any time during the trial
Frequency and intensity of adverse events, including serious adverse events and adverse events leading to discontinuation.
Time frame: From informed consent to end of trial
Changes in circulating levels of clinical chemistry and hematology parameters after 4, 8, 12 and 16 weeks of treatment.
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in serum prostate-specific antigen (PSA) levels after 4, 8, 12 and 16 weeks of treatment.
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in ECG parameters after 16 weeks of treatment.
Time frame: From baseline to the end of treatment at 16 weeks.
Changes in systolic and diastolic arterial blood pressure
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Proportion of participants with systolic blood pressure >140 mmHg and diastolic pressure >90 mmHg
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Proportion of participants with systolic blood pressure >160 mmHg and diastolic pressure >110 mmHg
Time frame: From baseline to 4 , 8, 12 and 16 weeks of treatment.
Changes in lipids and in carbohydrate metabolism parameters after 16 weeks of treatment
Time frame: From baseline to the end of treatment at 16 weeks.
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.
Time frame: From baseline to the end of treatment at 16 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Director study director
ReproNovo Aps
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leflutrozole, Dose 1, Leflutrozole, Dose 2 and Leflutrozole, Dose 3 in people with Semen Quality, run by ReproNovo Aps at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Public Disclosure (+45 32225466, publicdisclosure@repronovo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total motile sperm count (TMSC) after 16 weeks of treatment. (time frame: From baseline to the end of treatment at 16 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.