Phase 1 Study to Evaluate the Safety and Tolerability of Intravenously Administered PYC-003

Phase 1

Recruiting

• Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Interventions: Drug: PYC-003

• Registration Number: NCT06714006
• Lead Sponsor: PYC Therapeutics

Brief Summary

This is a Phase 1, First-in-Human study to evaluate the safety and tolerability of PYC-003 in healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD. There are 2 parts in this study, i.e. Part A and Part B.

Detailed Description

Part A (SAD - Healthy) will be conducted as a randomized, double-blind, placebo-controlled, SAD study to assess the safety, tolerability, PK, PD, and immunogenicity of PYC-003 in healthy adult participants. The anticipated number of participants across 3 Part A (SAD - Healthy) cohorts is approximately 24 participants. On Day 1, each participant will receive the investigational product (IP; ie, PYC-003 or placebo), as a single intravenous (IV) infusion. All Part A (SAD - Healthy) cohorts will first dose 2 sentinel participants in a blinded manner on Day 1.

Part B (SAD - ADPKD) will be conducted as an open-label SAD study to assess the safety, tolerability, PK, PD, and immunogenicity of PYC-003 in adult participants with confirmed PKD1mutation-associated ADPKD. The anticipated number of participants across 3 Part B (SAD - ADPKD) cohorts is approximately 18 participants. On Day 1, each participant will receive PYC-003 as a single IV infusion.

Study Timeline

• Study First Submitted: 2024-11-24
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-03
• Study Start: 2025-04-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A (SAD - Healthy)	PYC-003	Part A will be conducted as a randomized, double-blend, placebo-controlled, Single Ascending Dose Study to assess the safety, tolerability, Pharmacokinetic, Pharmacodynamic, and immunogenicity of PYC-003 in healthy adult participants
Part B (SAD - ADPKD)	PYC-003	Part B will be conducted as an open-label Single Ascending Dose study to assess the safety, tolerability, Pharmacokinetic, Pharmacodynamic, and immunogenicity of PYC-003 in adult participants with confirmed PKD1 mutation-associated ADPKD.

Primary Outcome Measures

Name	Time	Method
(Part A and B) Number of participants with treatment-related adverse events as assessed by CTCAE v4.0s	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1mutation-associated ADPKD. The incidence, severity, and relatedness of TEAEs and treatment-emergent SAEs will be recorded
(Part A and B) To evaluate the changes in Heart rate via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in ECG QTc interval from baseline via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in baseline pulse rate following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in baseline respiratory rate following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in ECG PR interval from baseline via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in ECG QRS duration from baseline via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes physically via complete and symptom-directed physical examination following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD Complete and symptom-directed physical examinations are to be performed by a licensed physician.; Complete physical examinations include general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.
(Part A and B) To evaluate the changes in ECG QT interval from baseline via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in baseline body temperature following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes in baseline systolic and diastolic blood pressure following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from baseline in serum potassium, serum magnesium, serum sodium, serum osmolality, serum cystatin C, and serum creatinine following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from baseline in urine potassium, urine magnesium, urine creatinine, and urine osmolality following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-6 following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-8 following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-10 following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, MCP-1 following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, TNF-α following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) To evaluate the changes from Baseline in cytokines, CXCL10 (IP-10)following a single dose of PYC-003 administered intravenously	24 weeks	To evaluate the safety and tolerability of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD

Secondary Outcome Measures

Name	Time	Method
(Part A and B) The peak plasma concentration, Cmax of PYC-003 following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, Tmax (time to reach max plasma concentration) of potential metabolites of PYC-003 would be determined following a single dose administered intravenously	24 weeks	To characterize the PK of potential metabolites of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, t½ (half life) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, AUC0-24 (Area under the plasma concentration versus time curve over the last 24 hour) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) Plasma PK parameter, AUC0-inf (extrapolated area under concentration-time curve) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, CL (Total drug clearance from plasma) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, AUC%extrap (the area under the curve) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, kel (elimination rate constant) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD
(Part A and B) The Plasma PK parameter, Vz (Volume of distribution) of PYC-003 will be determined following a single dose administered intravenously to adult participants	24 weeks	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for both healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD

Trial Locations

Locations (5)

South Coast Renal, Brockway House, Level 1, Suite 8, 82-86 Queen Street,; 🇦🇺 Southport, Gold Coast, Australia

Liverpool Hospital, Clinic G-Reception 133, Level 1, Clinical Building, Burnside Drive; 🇦🇺 Liverpool, New South Wales, Australia

Westmead Hospital, Clinical Research Unit, Level 6, B Wing/Building, Hawkesbury Road; 🇦🇺 Westmead, New South Wales, Australia

Doherty Clinical Trials (Satellite site for Liverpool Hospital), Level 2, 2 St Andrews Place; 🇦🇺 East Melbourne, Victoria, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia