Open Label, Dose Escalation, Repeat Dose Study Evaluating YCT-529 in Healthy Males

NCT06542237 | Recruiting Phase 1

• 1 other identifier: YCT-529-02
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b/2a open-label, dose escalation 3 part-study, 28-day, 90-day or 180 day repeat dose study of YCT-529 in healthy males who have decided to have a vasectomy and are waiting for the procedure and for men who have decided not to father children in the future. The study is aimed at evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and to assess sexual function and mood.

Conditions

Male Contraception

Keywords

male; non-hormonal; male contraception; healthy males; sperm count reduction; sperm motility; impaired spermatogenesis; impaired motility; orally administered; men; vasectomy; awaiting vasectomy; children; father; family planning

Outcome Measures

Primary Outcomes (59)

• The incidence and nature of any adverse events, dose-limiting adverse events and serious adverse adverse events.

  Assessment of the number and type of adverse events, dose-limiting adverse events and serious adverse events following dosing.

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Vital signs assessment (heart rate)

  Changes from pre-dose values (beats per minute)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Vital signs assessment (blood pressure)

  Changes from pre-dose values (mm hg)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Vital signs assessment (oral temperature)

  Changes from pre-dose values (temperature in celsius degrees)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• 12-lead ECG assessment (heart rate)

  Changes from pre-dose values (beats per minute)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• 12-lead ECG assessment (QT interval)

  Changes from pre-dose values for QT internal length (msec)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• 12-lead ECG assessment (QTcF Interval)

  Changes from pre-dose values for QTcF interval length (msec)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• 12-lead ECG assessment (PR Interval)

  Changes from pre-dose values for PR interval length (msec)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• 12-lead ECG assessment (QRS Duration)

  Changes from pre-dose values for QRS duration (msec)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Hemoglobin Blood Sample Test

  Change from pre-dose value for hemoglobin (gm/dl)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Hematocrit Blood Sample Test

  Change from pre-dose value for hematocrit (%)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Packed Cell Volume Blood Sample Test

  Change from pre-dose value for packed cell volume (%)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Red Blood Cell Sample Test

  Change from pre-dose value for red blood cells (g/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Mean Corpuscular Volume Blood Sample Test

  Change from pre-dose value for mean corpuscular volume (fL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Mean Corpuscular Hemoglobin Blood Sample Test

  Change from pre-dose value for mean corpuscular hemoglobin (MCH)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Mean Corpuscular Hemoglobin Concentration Blood Sample Test

  Change from pre-dose value for mean corpuscular hemoglobin concentration (g/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Platelet Count Blood Sample Test

  Change from pre-dose value for platelets (microL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- White Blood Cell Sample Test

  Change from pre-dose value for White blood cells (cells/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Neutrophil Blood Sample Test

  Change from pre-dose value for Neutrophils (cells/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Lymphocyte Blood Sample Test

  Change from pre-dose value for Lymphocytes (cells/mcL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Monocyte Blood Sample Test

  Change from pre-dose value for Monocytes (cells/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Eosinophil Blood Sample Test

  Change from pre-dose value for Eosinophils (%)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Basophil Blood Sample Test

  Change from pre-dose value for Basophils (%)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Coagulation Blood Sample Test

  Changes from pre-dose value for Prothrombin time (seconds)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Activated Partial Thromboplastin Time Blood Sample Test

  Changes from pre-dose values for Activated partial thromboplastin time (seconds)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Fibrinogen Blood Sample Test

  Changes from pre-dose value for Fibrinogen (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Sodium Blood Sample Tests

  Changes from pre-dose value for Sodium (mEq/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Chloride Blood Sample Test

  Changes from pre-dose value for Chloride (mmol/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Potassium Blood Sample Test

  Changes from pre-dose value for Potassium (mEq/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Bicarbonate Blood Sample Test

  Changes from pre-dose value for Bicarbonate (mEq/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Urea Blood Sample Test

  Changes from pre-dose value for Urea mmol/L

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Creatinine Blood Sample Test

  Changes from pre-dose value for Creatinine (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Bilirubin (total) Blood Sample Test

  Changes from pre-dose value for Bilirubin (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Bilirubin (direct) Blood Sample Test

  Changes from pre-dose value for Bilirubin, direct only if total bilirubin is elevated (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Alkaline Phosphatase Blood Sample Test

  Changes from pre-dose value for Alkaline Phosphatase (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Aspartate aminotransferase Blood Sample Test

  Changes from pre-dose value for Aspartate aminotransferase (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Alanine aminotransferase Blood Sample Test

  Changes from pre-dose value for Alanine aminotransferase (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Lactate dehydrogenase Blood Sample Test

  Changes from pre-dose value for Lactate dehydrogenase (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment -Creatinine Kinase Blood Sample Test

  Changes from pre-dose value for Creatine kinase for (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Gamma glutamyl transferase Blood Sample Test

  Changes from pre-dose value for Gamma glutamyl transferase (U/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Troponin Blood Sample Test

  Changes from pre-dose value for Troponin (ng/mL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Total Protein Blood Sample Test

  Changes from pre-dose value for Total Protein (g/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Albumin Blood Sample Test

  Changes from pre-dose value for Albumin (g/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Calcium Blood Sample Test

  Changes from pre-dose value for Calcium (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Fasting Glucose Blood Sample Test

  Changes from pre-dose value for Fasting Glucose (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Non Fasting Glucose Blood Sample Test

  Changes from pre-dose value for Non Fasting Glucose (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Fasting Triglycerides Blood Sample Test

  Changes from pre-dose value for Fasting Triglycerides (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment - Total Fasting Cholesterol Blood Sample Test

  Changes from pre-dose value for Total Fasting Cholesterol) (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment-Bilirubin Urine Sample Test

  Changes from pre-dose values for Bilirubin (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment-Urobilinogen Urine Sample Test

  Changes from pre-dose value for Urobilinogen (mmol/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Ketones Urine Sample Test

  Changes from pre-dose value for Ketones (mmol/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Glucose Urine Sample Test

  Changes from pre-dose value for Glucose (mmol/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Protein Urine Sample Test

  Changes from pre-dose values for Protein (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Blood Urine Sample Test

  Changes from pre-dose value for Blood (RBC/HPF)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Nitrites Urine Sample Test

  Changes from pre-dose value for Nitrites (mg/dL)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- pH Urine Sample Test

  Changes from pre-dose value for pH (pH value)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Specific Gravity Urine Sample Test

  Changes from pre-dose value for Specific Gravity (USG)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- Leukocytes Urine Sample Test

  Changes from pre-dose value for Leukocytes (leukocytes per microscopic field)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

• Clinical laboratory assessment- High Sensitivity C- Reactive Protein

  Changes from pre-dose value for High Sensitivity C- Reactive Protein (mg/L)

  For Part 1, from baseline to Day 280 and only in Part 2 from baseline to Day 360.

Secondary Outcomes (14)

• Plasma PK Parameter of YCT-529 (Area under the curve to Infinity [AUCinf])

  Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.

• Plasma PK Parameter of YCT-529 (Area under the curve to the last measured concentration [AUC0-t])

  Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.

• Plasma PK Parameter of YCT-529 (Area under the curve to 24 hours [AUC0-24])

  Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.

• Plasma PK Parameter of YCT-529 (Time to maximum concentration [Tmax])

  Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.

• Plasma PK Parameter of YCT-529 (Terminal elimination half life [T1/2])

  Pre-dose to 28 days post last dose in Part 1, and from pre-dose to 30 days post last dose in Parts 2 and 3.

Study Arms (1)

YCT-529

EXPERIMENTAL

Open label, dose escalation, 3 part study (Phase 1b includes Part 1; Phase 2a includes Parts 2 and 3).

Drug: YCT-529

Interventions

YCT-529 DRUG

In Part 1, 4 dosing cohorts and one optional 5th cohort with 4 participants each will be evaluated. In Part 2, up to 5 dosing cohorts and 2 optional cohorts with 4 participants each will be evaluated. Dose levels will be selected based on doses that were deemed safe and well tolerated upon 28-day administration in Part 1 and any previous Part 2 cohorts. In Part 3, 3 dosing cohorts and one optional 4th cohort with 10 participants each will receive doses within the range of doses that were deemed safe and well tolerated in Part 2.

YCT-529

Eligibility Criteria

• Age: 28 Years - 70 Years
• Gender Eligibility Details: Healthy male participants only
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant in good health as confirmed by physical examination, medical history, and clinical laboratory tests.
• Participant must provide written informed consent.
• Participant must be willing and able to communicate and participate in the whole study.
• Participant is 28 to 70 years of age (inclusive) at the time of consent.
• 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.
• Participant has a body mass index (BMI) 18.0 to 35.0 kg/m2.
• Participant has no history of hormonal therapy or 5-alpha reductase inhibitors use in the 90 days prior to the first screening visit.
• 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.
• Participant will refrain from donating blood or plasma during the study.
• 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.
• 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):
• million sperm cells/mL
• million sperm cells/total ejaculate
• % total motility
• % 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 \[WHO, 2021\]).

You may not qualify if:

• 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.
• Clinically significant abnormal physical and/or laboratory findings at Screening
• 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.
• 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) .
• Use of androgens and selective androgen receptor modulators (SARMs) within 90 days before first screening visit.
• Volunteers with a body weight \< 55 kg.
• Systolic blood pressure (BP) \>140 mmHg (\<45 years) or \>160 mmHg (≥45 years) and diastolic BP \>90 mmHg at screening and admission.
• 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.
• Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease or multiple endocrine deficiencies.
• 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).
• 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.
• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
• 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.
• 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.
• Known or suspected alcoholism or drug abuse within the last 2 years that may affect metabolism/transformation of steroid hormones or study treatment compliance.

Sponsors & Collaborators

• YourChoice Therapeutics, Inc.: lead

Study Sites (1)

New Zealand Clinical Research (NZCR)

Grafton, Auckland, 1010, New Zealand

RECRUITING

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 1

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Study Officials

• Rohit Katia, MBChB

  New Zealand Clinical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadja Mannowetz, PhD

CONTACT

415-233-6970; ClinicalTrial@ychoicetx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 3 parts: a 28-day Phase 1b part (Part 1), a 90-day Phase 2a part (Part 2) and a 180-day Phase 2a part (Part 3).

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: August 7, 2024
• Study Start: September 11, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

NZ (1)