Evaluating YCT-529 for male contraception in healthy men

Open Label Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Daily Oral Dosing of YCT-529 for 28 Days, 90 Days or 180 Days in Healthy Men

This study is testing a new male contraceptive called YCT-529 to see if it is safe and how it affects healthy men who don't want to have children.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Ages: 28 Years to 70 Years
• Sex: Male
• Sponsor: YourChoice Therapeutics, Inc. (Industry-sponsored)
• Locations: 1 site (Grafton, Auckland)
• Trial ID: NCT06542237 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter study evaluates the safety and tolerability of YCT-529 in healthy males who have decided to undergo a vasectomy or have chosen not to father children. The study consists of three parts, with participants receiving either a 28-day or 90-day repeat dose of the medication. It aims to assess pharmacokinetics, pharmacodynamics, sexual function, and mood. Participants will be dosed in either a fasted or fed state, with careful monitoring throughout the study.

Who should consider this trial

Good fit: Ideal candidates are healthy males aged 28 to 70 who have decided to have a vasectomy or are certain they do not want to father children.

Not a fit: Patients who are not considering vasectomy or do not have a firm decision against fathering children may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a non-hormonal male contraceptive option for men.

How similar studies have performed: While the approach is innovative, similar studies in non-hormonal male contraception have shown promise but are still largely untested in this specific context.

Eligibility criteria

Inclusion Criteria:

1. Participant in good health as confirmed by physical examination, medical history, and clinical laboratory tests.
2. Participant must provide written informed consent.
3. Participant must be willing and able to communicate and participate in the whole study.
4. Participant is 28 to 70 years of age (inclusive) at the time of consent.
5. Participant has decided to have a vasectomy and is waiting for the procedure or participant, in the opinion of the investigator, has made a firm decision not to father children in the future.
6. Participant has a body mass index (BMI) 18.0 to 35.0 kg/m2.
7. Participant has no history of hormonal therapy or 5-alpha reductase inhibitors use in the 90 days prior to the first screening visit.
8. Participant with partner(s) of childbearing potential agrees to use a method of contraception that is highly effective with any partner (i.e., total abstinence or at a minimum, barrier method plus additional method of contraception) during the study until 28 days after the last dose (Day 56 \[Part 1\] or Day 118 \[Parts 2 and 3\]). Condom use is required during the course of the study with partner(s) of both childbearing and non-childbearing potential until Day 56 (Part 1) or Day 118 (Parts 2 and 3) to avoid potential secondary transmission of study drug and ensure the safety of the participants' sexual partner(s). Total abstinence from intercourse during the course of the study until Day 56 (Part 1) or Day 118 (Parts 2 and 3) is considered an acceptable form of contraception if this is in line with participant's preferred and/or usual lifestyle. Condom use is not required while practicing total abstinence.
9. Participant will refrain from donating blood or plasma during the study.
10. Participant will not use cannabis or any other recreational drugs for at least 30 days before the Screening visit and during the study. The marijuana/cannabis test can be positive at Screening but needs to be negative at admission (Day -1) for a volunteer to be eligible for inclusion in the study.
11. Part 1: In the opinion of the investigator, participant is able to adhere to the study requirements, restrictions, schedule of assessments, and requirements related to sperm sample collection and maintenance of the sexual activity diary. Parts 2 and 3: In the opinion of the investigator, participant is able to adhere to the study requirements, restrictions, schedule of assessments, and requirements related to semen sample collection and maintenance of the electronic dosing diary.
12. Part 1: Participant providing at least 2 semen samples during the screening period with sperm parameters within at least the 5th percentile of the WHO range of normality (WHO, 2010 and WHO, 2021):

    * 15 million sperm cells/mL
    * 39 million sperm cells/total ejaculate
    * 40% total motility
    * 30% progressive motility Parts 2 and 3: Participant providing 3 semen samples during the screening period with ≥ 15 million sperm cells/mL (at least the 5th percentile of the WHO range of normality \[WHO, 2021\]).

Exclusion Criteria:

1. Men participating in another clinical study involving an investigational drug within the last 30 days prior to the first dosing or less than 5 elimination half-lives prior to first dosing, whichever is longer.
2. Clinically significant abnormal physical and/or laboratory findings at Screening
3. Abnormal serum chemistry values at screening or admission, that indicate liver or kidney dysfunction or that may be considered clinically significant as determined by the PI, except for bilirubin \>24 μmol/L and ALT, AST, GGT and ALP 2-fold above the upper limit of normal. Volunteers with known Gilbert's syndrome will be excluded if total bilirubin is ≥1.5 x ULN.
4. Evidence of renal impairment at screening, as indicated by an estimated eGFR of \<80 mL/min/1.73 m2 using the 2021 CKD-EPI Creatinine Equation (https://www.kidney.org/professionals/kdoqi/gfr\_calculator) .
5. Use of androgens and selective androgen receptor modulators (SARMs) within 90 days before first screening visit.
6. Volunteers with a body weight \< 55 kg.
7. Systolic blood pressure (BP) \>140 mmHg (\<45 years) or \>160 mmHg (≥45 years) and diastolic BP \>90 mmHg at screening and admission.
8. Clinically significant abnormal electrocardiogram (ECG) or a duration of corrected QT interval using Bazett's and Fridericia's QT correction methods in ECG (QTc) interval of \>450 msec at screening or predose.
9. Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease or multiple endocrine deficiencies.
10. Known history of significant cardiovascular, renal, hepatic (cholecystectomy is not permitted), or prostatic disease. Gilbert's syndrome is allowed (volunteer with known Gilbert's syndrome will be excluded if total bilirubin is ≥1.5 x ULN). If volunteer has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (i.e., direct bilirubin \<35% of the total bilirubin).
11. Current or clinically relevant history of any psychiatric disorder or clinical assessment of significant suicidal risk or risk of self-injury as per the Investigator's judgement.
12. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
13. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Seasonal allergies (e.g., hay fever) are allowed unless considered clinically significant by the investigator.
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results at screening visit.
15. Known or suspected alcoholism or drug abuse within the last 2 years that may affect metabolism/transformation of steroid hormones or study treatment compliance.
16. Volunteers who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening.
17. Regular alcohol consumption in males \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type.
18. Current smokers who have consumed at least 5 cigarettes or equivalent amount of nicotine per week within the last 3 months prior to Screening.
19. Confirmed positive drugs of abuse test result at Screening and admission and/or positive marijuana/cannabis test at admission (Day -1).
20. Participants and volunteers who are taking, or have taken, any prescribed or over-the-counter drug or vitamins/herbal remedies/supplements (other than up to 4 g of paracetamol or up to 3.2 g of ibuprofen per day during the 14 days before IMP administration). COVID-19 vaccines are accepted concomitant medications. Other concomitant medications may be accepted at the discretion of both the PI and the Sponsor. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardize the safety of the trial participant; and if the use of medication is not considered to interfere with the objectives of the study.
21. Male volunteer with pregnant or lactating partner(s).
22. Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
23. Any other medical condition that, in the opinion of the investigator, could alter the volunteer's well-being, the study conduct, or the interpretability of the results.

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Where this trial is running

Grafton, Auckland

• New Zealand Clinical Research (NZCR) — Grafton, Auckland, New Zealand (Recruiting)

Study contacts

• Principal investigator: Rohit Katia, MBChB — New Zealand Clinical Research
• Study coordinator: Nadja Mannowetz, PhD

Conditions Male Contraception; male; non-hormonal; male contraception; healthy males; sperm count reduction; sperm motility; impaired spermatogenesis