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

NCT06714006 | Recruiting Phase 1 DMC

• 1 other identifier: PYC-003-CL-001
• Study Type: interventional
• Target: 116
• Locations: 2 countries
• Sites: 9

Brief Summary

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

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Keywords

PKD1; Autosomal Dominant Polycystic Kidney Disease; ADPKD

Outcome Measures

Primary Outcomes (18)

• [Part A, B and C] Number of participants experiencing treatment emergent adverse events (AE) as assessed by CTCAE V5.0

  The incidence, severity, and relatedness of treatment emergent adverse events and treatment-emergent Serious Adverse Events will be recorded An AE is any event, side-effect, or other untoward medical occurrence that occurs in conjunction with the use of a medicinal product in humans, whether or not considered to have a causal relationship to this treatment. An AE can, therefore, be any unfavourable and unintended sign (that could include a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in vital signs (body temperature)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in vital signs (systolic and diastolic blood pressure)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in vital signs (pulse rate)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in vital signs (respiratory rate)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in 12-lead ECG (QT Interval)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in 12-lead ECG (QRS Duration)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in 12-lead ECG (QTcF Interval)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in 12-lead ECG (PR Interval)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in 12-lead ECG (Heart Rate)

  Up to 36 weeks

• [Part A, B and C] Changes from baseline in physical examination findings

  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. Abbreviated physical examinations will be symptom directed.

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in hepatic clinical chemistry parameters (ALT, AST, ALP and GGT)

  ALT (Alanine Transaminase), AST (Aspartate Transaminase) ALP (Alkaline Phosphatase) and GGT (Gamma-glutamyl transferase) will be tested

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in standard renal clinical chemistry parameters (eGFR)

  estimated Glomerular filtration rate (eGFR) will be calculated via the CKD EPI 2021 calculation

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in serum potassium, serum magnesium, and serum sodium

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in serum cystatin C

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in serum and urine creatinine

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in serum and urine osmolality

  Up to 36 weeks

• (Part A, B and C) Changes from baseline in urine magnesium and urine potassium

  Up to 36 weeks

Secondary Outcomes (10)

• [Part A, B and C] Peak plasma concentration (Cmax) of PYC003

  Up to 36 weeks

• [Part A, B and C] Time to maximum observed plasma drug concentration of PYC003

  Up to 36 weeks

• [Part A, B and C] Area under the plasma concentration-time curve, from time zero to 24 hours post dose of PYC-003 (AUC0-24)

  Up to 36 weeks

• [Part A, B and C] Area under the plasma concentration-time curve, from time zero to the last time point with measurable analyte concentration after PYC-003 dose (AUC0-last)

  Up to 36 weeks

• [Part A, B and C] Area under the plasma concentration-time curve, from time zero extrapolated to infinity (AUC0-inf)

  Up to 36 weeks

Study Arms (3)

Part A (SAD - Healthy)

PLACEBO COMPARATOR

Part A will be conducted as a randomized, double-blend, placebo-controlled, Single Ascending Dose Study in healthy adult participants. On Day 1, each participant will receive the investigational product (IP; i.e., 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.

Drug: PYC-003

Part B (SAD - ADPKD)

ACTIVE COMPARATOR

Part B will be conducted as an open-label Single Ascending Dose study in adult participants with confirmed PKD1 mutation-associated ADPKD. On Day 1, each participant will receive PYC-003 as a single IV infusion.

Drug: PYC-003

Part C (MAD - ADPKD)

ACTIVE COMPARATOR

Part C (MAD - ADPKD) will be conducted as an open-label MAD study in adult participants with confirmed PKD1 mutation-associated ADPKD. Each participant will receive PYC-003 as an IV infusion either once every 6 weeks for 13 weeks (i.e., dosing on Day 1, Day 43, and Day 85) or once every 8 weeks for 17 weeks (i.e., dosing on Day 1, Day 57, and Day 113).

Drug: PYC-003

Interventions

PYC-003 DRUG

A peptide-phosphorodiamidate morpholino oligonucleotide conjugate administered as a single intravenous infusion

Part A (SAD - Healthy); Part B (SAD - ADPKD); Part C (MAD - ADPKD)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Females who are pregnant, breastfeeding, or plan to become pregnant during the course of the study.
• Underlying physical or psychological medical condition that, in the opinion of the PI or designee, would make the participant unlikely to comply with the protocol or complete the study per protocol.
• Has only 1 kidney or has received a kidney transplant.
• Blood donation or had significant blood loss (\> 500 mL) within 30 days prior to the first administration of IP.
• Plasma donation within 7 days prior to the first administration of IP.
• Fever (body temperature \> 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to first administration of IP.
• Infections requiring parenteral antibiotics within 6 months prior to Screening.
• Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), HIV antibody.
• History of life-threatening infection (e.g., meningitis).
• Vaccination with a live vaccine within 4 weeks prior to the first administration of IP.
• Poor venous access.
• History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents.
• History of malignancy, except for non-melanoma skin cancer excised more than 1 year prior to Screening and cervical intraepithelial neoplasia that has been successfully cured more than 2 years prior to Screening.
• Abnormal electrocardiogram (ECG) findings at Screening, Day -3 to Day -1, or predose that are considered by the PI or designee to be clinically significant.
• History or presence of a condition associated with significant immunosuppression.

Sponsors & Collaborators

• PYC Therapeutics: lead

Study Sites (9)

South Coast Renal, Brockway House, Level 1, Suite 8, 82-86 Queen Street,

Southport, Gold Coast, 4125, Australia

RECRUITING

Liverpool Hospital, Clinic G-Reception 133, Level 1, Clinical Building, Burnside Drive

Liverpool, New South Wales, 2170, Australia

RECRUITING

Sydney Adventist Hospital

Wahroonga, New South Wales, 2076, Australia

RECRUITING

Westmead Hospital, Clinical Research Unit, Level 6, B Wing/Building, Hawkesbury Road

Westmead, New South Wales, 2145, Australia

RECRUITING

Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

RECRUITING

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3056, Australia

RECRUITING

Sunshine Hospital, Western Centre for Health Research and Education, Level 3, 176-190 Furlong Road

Saint Albans, Victoria, 3021, Australia

RECRUITING

Linear Clinical Research

Joondalup, Western Australia, 6027, Australia

RECRUITING

Pacific Clinical Research Network Auckland

Takapuna, Auckland, 0622, New Zealand

NOT YET RECRUITING

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Central Study Contacts

Sreenivasu Mudumba Chief Research & Development Officer, PhD

CONTACT

510-423-2680; pkd@pyctx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A will be randomized, double-blind, placebo-controlled, Single Ascending Dose study. Part B and Part C will be open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study comprises of 3 parts: Part A (SAD - Healthy) will be conducted as a randomized, double-blind, placebo-controlled, SAD study -and will enroll healthy adult participants. On Day 1, each participant will receive either PYC-003 or placebo, as a single intravenous (IV) infusion. Part B (SAD - ADPKD) will be conducted as an open-label SAD study in adult participants with confirmed PKD1 mutation-associated ADPKD. On Day 1, each participant will receive PYC-003 as a single IV infusion. Part C (MAD-ADPKD) will be conducted as an open label multiple ascending dose (MAD) study in adult participants with confirmed PKD1 mutation-associated ADPKD. Each participant will receive 3 doses of PYC-003 either 6 weeks or 8 weeks apart.

Study Record Dates

• First Submitted: November 24, 2024
• First Posted: December 3, 2024
• Study Start: April 7, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

AU (8); NZ (1)