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

NCT ID: NCT06714006

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-07

Study Completion Date

2026-01-31

Brief Summary

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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 2 parts in this study, i.e. Part A and Part B.

Detailed Description

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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.

Conditions

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Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study comprises of 2 parts:

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. On Day 1, each participant will receive either PYC-003 or placebo, as a single intravenous infusion.

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 PKD1 mutation-associated ADPKD. On Day 1, each participant will receive PYC-003 as a single IV infusion.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Part A will be randomized, double-blind, placebo-controlled, Single Ascending Dose study.

Part B will be open-label study.

Study Groups

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Part A (SAD - Healthy)

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

Group Type PLACEBO_COMPARATOR

PYC-003

Intervention Type DRUG

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

Part B (SAD - ADPKD)

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.

Group Type ACTIVE_COMPARATOR

PYC-003

Intervention Type DRUG

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

Interventions

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PYC-003

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female aged 18 to 65 years (inclusive) at the time of informed consent.
2. 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.
3. 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 \> 6 months prior to Screening, or MRI obtained during Pre-Screening).
4. BMI ≥ 18.0 and ≤ 32.0 kg/m2 and weight ≥ 50 kg.
5. Non-smoker and must not have used any tobacco or nicotine products within 2 months prior to Screening.
6. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 via the CKD EPI 2021 calculation (Inker et al. 2021).

8\. Hematology and serum chemistry results at Screening that meet the following criteria:

1. Platelets \> 150 × 10\^9/L
2. Total white blood cell count \> 3.0 × 10\^9/L
3. Absolute neutrophil count \> 1.5 × 10\^9/L
4. Hemoglobin \> 110 g/L for females and \> 120 g/L for males
5. Total and direct bilirubin \< 1.5 × ULN, unless elevated bilirubin is associated with a known benign condition (e.g., Gilbert's syndrome)
6. Alanine aminotransferase (ALT) \< 1.5 × ULN
7. Aspartate aminotransferase (AST) \< 1.5 × ULN
8. Alkaline phosphatase (ALP) \< 1.5 × ULN
9. Gamma-glutamyl transferase \< 2 × ULN Note: Screening laboratory testing may be repeated once at the discretion of the PI or designee to confirm out-of-range(exclusionary) results.

Exclusion Criteria

1. Presence of potentially confounding genetic mutations (per genotyping by a NATA accredited or equivalent diagnostic laboratory)including, but not limited to, the presence of PKD2, HNF1B, GANAB, IFT140, and/or DNAJB 11 mutations. Note: Where genotyping is not included the medical history for a participant, genotyping may be completed at Pre-Screening.
2. Use of (or anticipated use of) Tolvaptan and/or metformin administration within 30 days prior to the first administration of IP until study completion.
3. Any renal or systemic pathology other than ADPKD or any other condition or prior therapy that in the opinion of the PI or designee would make the participant unsuitable for this study.
4. Has only 1 kidney or has a kidney transplant.
5. History of borderline to low blood magnesium and potassium levels and/or Screening or Day -1 blood magnesium level \< 0.7 mmol/L and potassium levels \< 3.5 mmol/L.

Note: Repeat testing (i.e., 1 repeat per parameter) at Screening or Day -1 is permitted for out-of-range values following approval by the PI or designee.
6. Proteinuria \> 500 milligrams per 24 hours.
7. Hematuria (urine albumin:creatinine ratio \> 30 mg/mmoL, or hematuria \> ++ on dipstick, or \> 100 cells per high-power field on microscopy)and/or urinary abnormalities at Screening deemed by the PI or designee to be of moderate or higher severity.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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PYC Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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

Southport, Gold Coast, Australia

Site Status RECRUITING

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

Liverpool, New South Wales, Australia

Site Status RECRUITING

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

Westmead, New South Wales, Australia

Site Status RECRUITING

Mater Hospital Brisbane

South Brisbane, Queensland, Australia

Site Status RECRUITING

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

Saint Albans, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Joondalup, Western Australia, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Sreenivasu Mudumba Chief Research & Development Officer, PhD

Role: CONTACT

510-423-2680

Facility Contacts

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Judy Coote

Role: primary

+61 7 5591 2611

Belinda Yip

Role: primary

+61 2 8738 7103

Penny Murie

Role: primary

+61 2 8890 6848

Kate O'Neill

Role: primary

+61 7 3163 6694

Shannon Kokoszka

Role: primary

+61 3 9970 4200

Brayden Ceravolo

Role: primary

1300 546 327 / 08 6382 5110

Other Identifiers

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PYC-003-CL-001

Identifier Type: -

Identifier Source: org_study_id

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