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

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

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Intervention / Treatment: Drug: PYC-003

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 4 Part A (SAD - Healthy) cohorts is approximately 32 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 single ascending dose (SAD) study to assess the safety, tolerability, PK, PD, and immunogenicity of PYC-003 in adult participants with confirmed PKD1 mutation-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.

Part C (MAD-ADPKD) will be conducted as an open label multiple ascending dose (MAD) study to assess the safety, tolerability, PK, PD, and immunogenicity of PYC-003 in adult participants with confirmed PKD1 mutation-associated ADPKD. The anticipated number of participants across 2 Part C (MAD - ADPKD) cohorts is approximately 24 participants. 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).

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sreenivasu Mudumba Chief Research & Development Officer, PhD; Phone Number: 510-423-2680; Email: pkd@pyctx.com

Study Locations

• Australia
  • Gold Coast
    • Southport, Gold Coast, Australia, 4125
      • Recruiting
      • South Coast Renal, Brockway House, Level 1, Suite 8, 82-86 Queen Street,
      • Principal Investigator: Jagadeesh Kurtkoti
      • Contact: Judy Coote; Phone Number: +61 7 5591 2611; Email: judy.coote@brockway.com.au
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Not yet recruiting
      • Concord Repatriation General Hospital
      • Contact: Helen Clayton; Phone Number: + 61 2 9767 6576; Email: SLHD-ConcordRenalResearch@health.nsw.gov.au
      • Principal Investigator: Shaundeep Sen
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital, Clinic G-Reception 133, Level 1, Clinical Building, Burnside Drive
      • Principal Investigator: Angela Makris
      • Contact: Belinda Yip; Phone Number: +61 2 8738 7103; Email: belinda.yip@health.nsw.gov.au
    • Wahroonga, New South Wales, Australia, 2076
      • Recruiting
      • Sydney Adventist Hospital
      • Contact: Caitlin Cirera; Phone Number: +61 2 9480 6283; Email: caitleen.cirera@sah.org.au
      • Principal Investigator: Muhgeot Wong
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital, Clinical Research Unit, Level 6, B Wing/Building, Hawkesbury Road
      • Principal Investigator: Gopala Rangan
      • Contact: Penny Murie; Phone Number: +61 2 8890 6848; Email: penelope.murie@health.nsw.gov.au
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Mater Hospital Brisbane
      • Principal Investigator: Michael Burke
      • Contact: Kate O'Neill; Phone Number: +61 7 3163 6694; Email: kate.oneill@mater.org.au
  • Victoria
    • Fitzroy, Victoria, Australia, 3056
      • Recruiting
      • St Vincent's Hospital Melbourne
      • Contact: Stephanie Thatcher; Phone Number: +61 427 652 661; Email: Nephrology.Research@svha.org.au
      • Principal Investigator: Veena Roberts, Dr
    • Saint Albans, Victoria, Australia, 3021
      • Recruiting
      • Sunshine Hospital, Western Centre for Health Research and Education, Level 3, 176-190 Furlong Road
      • Principal Investigator: Eugenia Pedagogos
      • Contact: Shannon Kokoszka; Phone Number: +61 3 9970 4200; Email: shannon.kokoszka@wh.org.au
  • Western Australia
    • Joondalup, Western Australia, Australia, 6027
      • Recruiting
      • Linear Clinical Research
      • Principal Investigator: Dr Lara Hatchuel
      • Sub-Investigator: Dr Hemant Kulkarni
      • Contact: Brayden Ceravolo; Phone Number: 1300 546 327 / 08 6382 5110; Email: enquiries@linear.org.au; bceravolo@linear.org.au
• New Zealand
  • Auckland
    • Takapuna, Auckland, New Zealand, 0622
      • Recruiting
      • Pacific Clinical Research Network Auckland
      • Contact: Paul Hamilton, Dr; Phone Number: +64 22 585 0357; Email: paulhamilton@pcrn.co.nz
      • Principal Investigator: Paul Hamilton, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Part A (SAD - Healthy Volunteers) Key Inclusion Criteria

1. Adult aged 18 to 60 years (inclusive)
2. 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
3. BMI ≥ 18.0 and ≤ 32.0 kg/m2 and weight ≥ 50 kg.
4. Non-smoker and must not have used any tobacco or nicotine products within 2 months prior to Screening.
5. Clinical laboratory values within normal range or deemed not clinically significant by the PI
6. eGFR ≥ 80 mL/min/1.73 m2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) 2021 calculation
7. 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.
8. 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.
9. Females must agree not to donate ova from the first administration of IP until 30 days following study completion.
10. Males must agree not donate sperm from the first administration of IP until 90 days following study completion.
11. Able and willing to attend the necessary visits to the study site.
12. Able and willing to adhere to caffeine, alcohol, and nicotine-containing product restrictions
13. 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.

Part A (SAD - Healthy Volunteers) Key Exclusion Criteria

1. Females who are pregnant, breastfeeding, or plan to become pregnant during the course of the study.
2. 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.
3. Has only 1 kidney or has received a kidney transplant.
4. Blood donation or had significant blood loss (> 500 mL) within 30 days prior to the first administration of IP.
5. Plasma donation within 7 days prior to the first administration of IP.
6. Fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to first administration of IP.
7. Infections requiring parenteral antibiotics within 6 months prior to Screening.
8. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), HIV antibody.
9. History of life-threatening infection (e.g., meningitis).
10. Vaccination with a live vaccine within 4 weeks prior to the first administration of IP.
11. Poor venous access.
12. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents.
13. 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.
14. 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.
15. History or presence of a condition associated with significant immunosuppression.
16. Exposure to any drugs that cause significant immunosuppression (including experimental therapies as part of a clinical study) within 4 months or 5 half-lives (whichever is longer), prior to Screening.
17. ALP, AST, and ALT > 1.5 × ULN at Screening or Day -3 to Day -1.
18. History of borderline to low blood magnesium and potassium levels and/or Screening or Day -3 to Day -1 blood magnesium level < 0.7 mmol/L and potassium levels < 3.5 mmol/L.
19. Active infection of the urinary tract (ie, kidney, bladder).
20. Positive toxicology screening panel (urine test including qualitative identification of amphetamines, barbiturates, benzodiazepines, cocaine, methamphetamine, methadone, opiates, phencyclidine, tetrahydrocannabinol [THC], tricyclic antidepressants), or alcohol breath test.
21. History of substance abuse or dependency or history of recreational IV drug use over the last 5 years (by self-declaration).
22. Regular alcohol consumption defined as > 14 standard drinks per week for females and > 21 standard drinks for males (where 1 standard drink = 375 mL of mid-strength beer [3.5% alcohol/volume], 100 mL wine [13.5% alcohol/volume] or 30 mL of spirits [40% alcohol/volume]) or > 4 standard drinks on any single day.
23. Unwilling to abstain from alcohol for 48 hours prior to admission to the study site and for 48 hours prior to any follow-up visits.
24. Use of any investigational medical device or investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first administration of IP.

25. Use of (or anticipated use of) the following:

    1. Any prescription drugs (other than hormonal contraception; oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring, or an intrauterine device [IUD]) within 14 days prior to the first administration of IP and during the course of the study without prior approval of the PI and MM.
    2. Any over-the-counter medication, herbal remedies, supplements or vitamins within 7 days prior to the first administration of IP and during the course of the study without prior approval of the PI and MM. Note: Paracetamol (i.e., up to 2000 mg per day) may be used for minor ailments during the study, at the discretion of the PI, without prior consultation with the MM.
26. Unwilling to refrain from strenuous exercise (including weightlifting) for 48 hours prior to admission to the study site and for 48 hours prior to any follow-up visits.
27. Anything that the PI considers would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.

Part B and Part C (ADPKD Participants) 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 prior to Screening, or MRI obtained during Pre-Screening).
4. BMI ≥ 18.0 and ≤ 35.0 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

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

   9.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.

   12.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.

   Part B and Part C (ADPKD Participant) Key Exclusion Criteria

   1. Females who are pregnant, breastfeeding, or plan to become pregnant during the course of the study.
   2. 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.
   3. Use of (or anticipated use of) Tolvaptan and/or metformin administration within 30 days prior to the first administration of IP until study completion.
   4. 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.
   5. 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.
   6. Has only 1 kidney or has a kidney transplant.
   7. Blood donation or had significant blood loss (> 500 mL) within 30 days prior to the first administration of IP.
   8. Plasma donation within 7 days prior to the first administration of IP.
   9. Has received (or is anticipated to receive) cell therapy, gene therapy, or RNA therapy for any renal condition.
   10. Fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to first administration of IP.
   11. Infections requiring parenteral antibiotics within 6 months prior to Screening.
   12. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), HIV antibody.
   13. History of life-threatening infection (e.g., meningitis).
   14. Vaccination with a live vaccine within 4 weeks prior to the first administration of IP.
   15. Poor venous access.
   16. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents.
   17. 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.
   18. Abnormal ECG findings at Screening, Day -3 to Day -1, or predose that are considered by the PI or designee to be clinically significant.

   19. Abnormal vital signs findings at Screening that are considered by the PI or designee to be clinically significant.

       Note: A hypertensive participant is eligible if on a stable antihypertensive regimen for ≥ 28 days prior to first administration of IP and the blood pressure adequately controlled (per PI discretion) prior to first administration of IP.

   20. History or presence of a condition associated with significant immunosuppression.
   21. Exposure to any drugs that cause significant immunosuppression (including experimental therapies as part of a clinical study) within 4 months or 5 half-lives (whichever is longer), prior to Screening.
   22. History of borderline to low blood magnesium and potassium levels and/or Screening or Day -3 to Day -1 blood magnesium level < 0.7 mmol/L and potassium levels < 3.5 mmol/L.
   23. Urine protein: creatinine ratio (UPCR) of > 50 mg/mmol.
   24. Hematuria (urine protein: 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.
   25. Renal complications (eg, cyst rupture or cyst infections) within 6 weeks prior to first administration of IP.
   26. Active infection of the urinary tract (ie, kidney, bladder).
   27. Positive toxicology screening panel (urine test including qualitative identification of amphetamines, barbiturates, benzodiazepines, cocaine, methamphetamine, methadone, opiates, phencyclidine, tetrahydrocannabinol [THC], tricyclic antidepressants), or alcohol breath test.
   28. History of substance abuse or dependency or history of recreational IV drug use over the last 5 years (by self-declaration).
   29. Regular alcohol consumption defined as > 14 standard drinks per week for females and > 21 standard drinks for males (where 1 standard drink = 375 mL of mid-strength beer [3.5% alcohol/volume], 100 mL wine [13.5% alcohol/volume] or 30 mL of spirits [40% alcohol/volume]) or > 4 standard drinks on any single day.
   30. Unwilling to abstain from alcohol for 48 hours prior to admission to the study site and for 48 hours prior to any follow-up visits.
   31. Use of any investigational medical device or investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first administration of IP.
   32. Unwilling to refrain from strenuous exercise (including weightlifting) for 48 hours prior to admission to the study site and for 48 hours prior to any follow-up visits.
   33. Anything that the PI considers would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A (SAD - Healthy); 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; A peptide-phosphorodiamidate morpholino oligonucleotide conjugate administered as a single intravenous infusion
Active Comparator: Part B (SAD - ADPKD); 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; A peptide-phosphorodiamidate morpholino oligonucleotide conjugate administered as a single intravenous infusion
Active Comparator: Part C (MAD - ADPKD); 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; A peptide-phosphorodiamidate morpholino oligonucleotide conjugate administered as a single intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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 Outcome Measures

Outcome Measure	Time Frame
[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
[Part A, B and C] The percentage of the AUC that was extrapolated beyond the last observed data point (AUC%extrap)	Up to 36 weeks
[Part A, B and C] Apparent half life of PYC-003 (T1/2)	Up to 36 weeks
[Part A, B and C] Apparent elimination constant (Kel) of PYC-003	Up to 36 weeks
[Part A, B and C] Apparent clearance (CL) of PYC-003	Up to 36 weeks
[Part A, B and C] Apparent volume of distribution (Vz) of PYC-003	Up to 36 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A and B) The Plasma PK parameter, Cmax (Max plasma drug concentration) of potential metabolites of PYC-003 would be determined following a single dose administered intravenously	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	24 weeks
(Part A and B) The Plasma PK parameter, AUC (total drug exposure integrated over time) of potential metabolites of PYC-003 would be determined following a single dose administered intravenously	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	24 weeks
(Part A and B)The number and percentage of participants who develop ADAs and NAbs following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	To the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) To evaluate the changes from baseline in urine biomarker, NGAL of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	To evaluate the PD effect and duration of the PD effect of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) The Urine PK Parameter, fet1-t2 (fraction of intravenously administered drug excreted in urine within timespan t1 to t2) of PYC-003 will be determined following a single dose administered intravenously to adult participants	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part B) Advanced imaging based biometric biomarker, CPSA (cyst parenchyma surface area) following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD	To determine the effect of PYC-003 on surrogate endpoint markers following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) The Urine PK Parameter, CLr (renal clearance of drug from plasma) will be determined following a single dose administered intravenously to adult participants	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) The Urine PK Parameter, Aet1-t2 (Amount of unchanged drug excreted in urine within timespan t1 to t2) of PYC-003 will be determined following a single dose administered intravenously	This is done to characterize the PK of PYC-003 in participants following a single dose administered intravenously, for healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part B) Advanced imaging based biometric biomarker, TCN (total cyst number) following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD	To determine the effect of PYC-003 on surrogate endpoint markers following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part B) Advanced imaging based biometric biomarker, hTKV (height adjusted Total Kidney Volume) following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD	To determine the effect of PYC-003 on surrogate endpoint markers following single dose intravenous administration to adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) To evaluate the changes from baseline in urine biomarker, PC1 of PYC-003 following a single dose administered intravenously	To evaluate the PD effect and duration of the PD effect of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) To evaluate the changes from Baseline in Urine Biomarkers, KIM1 following a single dose of PYC-003 administered intravenously	To evaluate the PD effect and duration of the PD effect of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part B) To evaluate the changes from Baseline in Serum Biomarkers, creatinine following a single dose of PYC-003 administered intravenously to adult participants with confirmed PKD1 mutation-associated ADPKD.	To evaluate the PD effect and duration of the PD effect of PYC-003 following a single dose administered intravenously to adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part B) To evaluate the changes from Baseline in serum Biomarkers, cystatin C following a single dose of PYC-003 administered intravenously to adult participants with confirmed PKD1 mutation-associated ADPKD.	To evaluate the PD effect and duration of the PD effect of PYC-003 following a single dose administered intravenously to adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-6 following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, CXCL10 (IP-10)following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD.	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, TNF-α following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, MCP-1 following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-10 following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks
(Part A and B) To evaluate the changes from Baseline in cytokines, IL-8 following a single dose of PYC-003 administered intravenously	To evaluate the immunogenicity of PYC-003 following a single dose administered intravenously to healthy adult participants and adult participants with confirmed PKD1 mutation-associated ADPKD	24 weeks

Collaborators and Investigators

• Sponsor: PYC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 24, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ADPKD; Autosomal Dominant Polycystic Kidney Disease; PKD1
• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Polycystic Kidney Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Polycystic Kidney, Autosomal Dominant
• Other Study ID Numbers: PYC-003-CL-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No