A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenously Administered PYC-003, a Peptide-phosphorodiamidate Morpholino Oligonucleotide Conjugate, in Healthy Adult Participants and Adult Participants With Confirmed PKD1 Mutation-associated Autosomal Dominant Polycystic Kidney Disease
This is a Phase 1, First-in-Human study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of PYC-003 in healthy adult participants and adult participants with confirmed PKD1 mutation-associated Autosomal Dominant Polycystic Kidney Disease (ADPKD) There are 3 parts in this study, i.e. Part A, Part B and Part C
• Adult aged 18 to 60 years (inclusive)
• At the discretion of the PI or designee, in good general health, with no significant medical history, and have no clinically significant abnormalities on physical examination at Screening
• BMI ≥ 18.0 and ≤ 32.0 kg/m2 and weight ≥ 50 kg.
• Non-smoker and must not have used any tobacco or nicotine products within 2 months prior to Screening.
• Clinical laboratory values within normal range or deemed not clinically significant by the PI
• eGFR ≥ 80 mL/min/1.73 m2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) 2021 calculation
• Woman of childbearing potential (WOBCP) must agree to use an acceptable, highly effective, double barrier method of contraception from the start of Screening until study completion.
• Males must be surgically sterile (vasectomized for at least 6 months prior to first IP administration) or, if engaged in sexual relations with a WOCBP, must agree to use an acceptable, highly effective, double barrier method of contraception from the start of Screening until study completion.
• Females must agree not to donate ova from the first administration of IP until 30 days following study completion.
⁃ Males must agree not donate sperm from the first administration of IP until 90 days following study completion.
⁃ Able and willing to attend the necessary visits to the study site.
⁃ Able and willing to adhere to caffeine, alcohol, and nicotine-containing product restrictions
⁃ Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
• Male or female aged 18 to 65 years (inclusive) at the time of informed consent.
• ADPKD diagnosis as confirmed by the presence of genetic mutations associated with ADPKD, including, but not limited to, the presence of PKD1 mutation. Note: Where genotyping is not included the medical history for a participant, genotyping may be completed at Pre-Screening.
• Class 1C, 1D, or 1E per Mayo Imaging Classification System for Predicting Kidney Outcomes in ADPKD (Irazabal et al. 2015) (based upon prior magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan obtained prior to Screening, or MRI obtained during Pre-Screening).
• BMI ≥ 18.0 and ≤ 35.0 kg/m2 and weight ≥ 50 kg.
• Non-smoker and must not have used any tobacco or nicotine products within 2 months prior to Screening.
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 via the CKD EPI 2021 calculation
• 8\. Hematology and serum chemistry results at Screening that meet the following criteria:
• Platelets \> 150 × 10\^9/L
• Total white blood cell count \> 3.0 × 10\^9/L
• Absolute neutrophil count \> 1.5 × 10\^9/L
• Hemoglobin \> 110 g/L for females and \> 120 g/L for males
• Total and direct bilirubin \< 1.5 × ULN, unless elevated bilirubin is associated with a known benign condition (e.g., Gilbert's syndrome)
• Alanine aminotransferase (ALT) \< 1.5 × ULN
• Aspartate aminotransferase (AST) \< 1.5 × ULN
• Alkaline phosphatase (ALP) \< 1.5 × ULN
• Gamma-glutamyl transferase \< 2 × ULN
‣ WOCBP must agree to use an acceptable, highly effective, double barrier method of contraception from the start of Screening until study completion
• 10\. Males must be surgically sterile (vasectomized for at least 6 months prior to first administration of IP) or, if engaged in sexual relations with a WOCBP, must agree to use an acceptable, highly effective, double barrier method of contraception from the start of Screening until study completion
• 11\. Females must agree not to donate ova from the first administration of IP until 30 days following study completion.
∙ Males must agree not donate sperm from the first administration of IP until 90 days following study completion.
• 13\. Able and willing to attend the necessary visits to the study site.
• 14\. Able and willing to adhere to alcohol and nicotine-containing product restrictions
• 15\. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.