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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06714006




Registration number
NCT06714006
Ethics application status
Date submitted
24/11/2024
Date registered
3/12/2024
Date last updated
4/07/2025

Titles & IDs
Public title
Phase 1 Study to Evaluate the Safety and Tolerability of Intravenously Administered PYC-003
Scientific title
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
Secondary ID [1] 0 0
PYC-003-CL-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney Disease (ADPKD) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PYC-003

Placebo comparator: 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

Active comparator: 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.


Treatment: Drugs: PYC-003
A peptide-phosphorodiamidate morpholino oligonucleotide conjugate administered as a single intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
(Part A and B) Number of participants with treatment-related adverse events as assessed by CTCAE V5.0
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
(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
Timepoint [2] 0 0
24 weeks
Primary outcome [3] 0 0
(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
Timepoint [3] 0 0
24 weeks
Primary outcome [4] 0 0
(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
Timepoint [4] 0 0
24 weeks
Primary outcome [5] 0 0
(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
Timepoint [5] 0 0
24 weeks
Primary outcome [6] 0 0
(Part A and B) To evaluate the changes in ECG QTcF interval from baseline via 12-lead ECG (local) following a single dose of PYC-003 administered intravenously
Timepoint [6] 0 0
24 weeks
Primary outcome [7] 0 0
(Part A and B) To evaluate the changes in baseline body temperature following a single dose of PYC-003 administered intravenously
Timepoint [7] 0 0
24 weeks
Primary outcome [8] 0 0
(Part A and B) To evaluate the changes in baseline systolic and diastolic blood pressure following a single dose of PYC-003 administered intravenously
Timepoint [8] 0 0
24 weeks
Primary outcome [9] 0 0
(Part A and B) To evaluate the changes in baseline pulse rate following a single dose of PYC-003 administered intravenously
Timepoint [9] 0 0
24 weeks
Primary outcome [10] 0 0
(Part A and B) To evaluate the changes in baseline respiratory rate following a single dose of PYC-003 administered intravenously
Timepoint [10] 0 0
24 weeks
Primary outcome [11] 0 0
(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
Timepoint [11] 0 0
24 weeks
Primary outcome [12] 0 0
(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
Timepoint [12] 0 0
24 weeks
Primary outcome [13] 0 0
(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
Timepoint [13] 0 0
24 weeks
Primary outcome [14] 0 0
(Part A and B) To evaluate the changes in standard renal and hepatic clinical chemistry parameters following a single dose of PYC-003 administered intravenously
Timepoint [14] 0 0
24 weeks
Secondary outcome [1] 0 0
(Part A and B) The peak plasma concentration, Cmax of PYC-003 following a single dose administered intravenously
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
(Part A and B) The peak plasma concentration, Tmax (time to maximum observed plasma drug concentration) of PYC-003 following a single dose administered intravenously
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
(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
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
(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
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
(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
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
(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
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
(Part A and B) The Plasma PK parameter, kel (elimination rate constant) of PYC-003 will be determined following a single dose administered intravenously
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
(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
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
(Part A and B) The Plasma PK parameter, Vz (Volume of distribution) of PYC-003 will be determined following a single dose administered intravenously
Timepoint [9] 0 0
24 weeks

Eligibility
Key inclusion criteria
Inclusion Criteria (Part A):

* Male or female aged 18 to 60 years (inclusive) at the time of informed consent.
* 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 and/or before the first administration of IP
* BMI between = 18.0 and = 32.0 kg/m2 and weight = 50 kg
* Nonsmoker and must not have used any tobacco products within 2 months prior to Screening.
* Clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee
* Estimated glomerular filtration rate (eGFR) = 80 mL/min/1.73 m2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) 2021 calculation
* Women of childbearing potential (WOCBP) 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 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

Inclusion Criteria (Part B):

* Male or female aged 18 to 60 years (inclusive) at the time of informed consent.
* ADPKD diagnosis based on Ravine Pei diagnosis criteria (Pei et al. 2009):

1. Presence of = 3 (unilateral or bilateral) renal cysts for participants aged = 39 years.
2. Presence of = 2 renal cysts in each kidney for participants aged 40 to 55 years (inclusive).
* ADPKD diagnosis as confirmed by the presence of genetic mutations associated with ADPKD (per genotyping by a National Association of Testing Authorities [NATA] accredited or equivalent diagnostic laboratory) 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 Screening.

* 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 Screening).
* BMI between = 18.0 and = 32.0 kg/m2 and weight = 50 kg.
* Nonsmoker and must not have used any tobacco products within 2 months prior to Screening.
* Estimated glomerular filtration rate (eGFR) = 30 mL/min/1.73 m2 via the CKD EPI 2021 calculation
* Hematology and serum chemistry results at Screening that meet the following criteria:

1. Platelets > 150 × 109/L.
2. Total white blood cell count > 3.0 × 10^9/L.
3. Absolute neutrophil count > 1.5 × 10^9/L.
4. Hemoglobin > 110g/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.
* WOCBP 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 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.
* 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.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria (Part A):

* 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 has 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 (eg, 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 ECG findings at Screening, 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
* 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.
* ALP, AST, and ALT >1.5 × ULN at Screening or Day -1
* History of borderline to low blood magnesium and potassium levels and/or Screening or Day -1 blood magnesium and potassium levels <0.7mmol/L and potassium levels < 3.5mmol/L
* Active infection of the urinary tract (ie, kidney, bladder).
* 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.
* History of substance abuse or dependency or history of recreational IV drug use over the last 5 years (by self-declaration).
* 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.
* 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.
* 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.
* 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.
* 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.
* Anything that the PI considers would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.

Exclusion Criteria (Part B):

1. Females who are pregnant 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, HFN1B, 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 received 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 -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 -1 blood magnesium level < 0.7 mmol/L and potassium levels < 3.5 mmol/L.

Note: Repeat testing (ie, 1 repeat per parameter) at Screening or Day -1 is permitted for out-of-range values following approval by the PI or designee.
23. Proteinuria > 500 milligrams per 24 hours.
24. 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.
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/04/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2026
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Gold CoastNSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
South Coast Renal, Brockway House, Level 1, Suite 8, 82-86 Queen Street, - Southport
Recruitment hospital [2] 0 0
Liverpool Hospital, Clinic G-Reception 133, Level 1, Clinical Building, Burnside Drive - Liverpool
Recruitment hospital [3] 0 0
Westmead Hospital, Clinical Research Unit, Level 6, B Wing/Building, Hawkesbury Road - Westmead
Recruitment hospital [4] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [5] 0 0
Doherty Clinical Trials (Satellite site for Sunshine Hospital), Level 2, 2 St Andrews Place - East Melbourne
Recruitment hospital [6] 0 0
Linear Clinical Research - Joondalup
Recruitment postcode(s) [1] 0 0
4125 - Southport
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
3002 - East Melbourne
Recruitment postcode(s) [6] 0 0
6027 - Joondalup

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PYC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sreenivasu Mudumba Chief Research & Development Officer, PhD
Address 0 0
Country 0 0
Phone 0 0
510-423-2680
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06714006