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

PYC Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Treatments: Drug: PYC-003

Study type: Interventional

Funder types: Industry

Identifiers

NCT06714006

PYC-003-CL-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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56 participants in 2 patient groups, including a placebo group

Part A (SAD - Healthy)

Placebo Comparator group

Description:

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

Treatment:

Drug: PYC-003

Part B (SAD - ADPKD)

Active Comparator group

Description:

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.

Treatment:

Drug: PYC-003