Safety, Tolerability and Pharmacokinetics of AZD1613 in Adults With Autosomal Dominant Polycystic Kidney Disease (PIONEER-PKD)

A Phase I Randomised, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD1613 Following Multiple Ascending Dose Administration in Participants With Autosomal Dominant Polycystic Kidney Disease

A study to investigate safety, tolerability, and pharmacokinetics of AZD1613 following subcutaneous or intravenous administration in participants with autosomal dominant polycystic kidney disease (ADPKD).

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Polycystic Kidney Disease
• Intervention / Treatment: Drug: AZD1613 - Part A; Drug: Placebo - Part A; Drug: AZD1613 - Part B; Drug: Placebo - Part B

Detailed Description

This Phase I, randomised, single-blind, placebo-controlled study will assess the safety and tolerability of AZD1613 and characterise the pharmacokinetics (PK) of AZD1613 in participants with autosomal dominant polycystic kidney disease (ADPKD), following subcutaneous (SC) or intravenous (IV) administration. Inclusion of participants receiving placebo is appropriate for benchmarking the safety and tolerability of AZD1613. Furthermore, the safety and PK profile will be evaluated in Chinese participants with ADPKD to assess any potential race effect in this population.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Chengdu, China, 610072
    • Not yet recruiting
    • Research Site
  • Hangzhou, China, 310003
    • Not yet recruiting
    • Research Site
  • Nanjing, China, 210009
    • Not yet recruiting
    • Research Site
  • Shanghai, China, 200025
    • Not yet recruiting
    • Research Site
  • Wuhan, China, 430022
    • Not yet recruiting
    • Research Site
  • Xiamen, China, 361101
    • Not yet recruiting
    • Research Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Not yet recruiting
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Not yet recruiting
      • Research Site
  • California
    • Loma Linda, California, United States, 92354
      • Not yet recruiting
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Not yet recruiting
      • Research Site
    • Orlando, Florida, United States, 32808
      • Recruiting
      • Research Site
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Not yet recruiting
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78212
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with ADPKD Mayo Class (IB-IE), as per clinical diagnosis (MIC) assessed centrally. Genetic testing results will not be used for eligibility purposes
• eGFR = 45 to 90 mL/min /1.73m2
• Body weight ≥ 45 kg and body mass index within the range 18 to 35 kg/m2 (inclusive).
• Females are to be of non-childbearing potential

Exclusion Criteria:

• As judged by the investigator, any evidence of cardiac, vascular, and other renal conditions which in the investigator's opinion makes it undesirable for the participant to participate in the study.
• Positive hepatitis C antibody, hepatitis B virus surface antigen, or human immunodeficiency virus test, at screening.
• History of QT prolongation associated with other medications that required discontinuation of that medication.
• Congenital long QT syndrome.
• History of ventricular arrhythmia requiring treatment. Patients with atrial fibrillation/flutter and controlled ventricular rate HR < 100 bpm can be eligible as judged by the investigator.
• Haemoglobin below the lower limit of the normal range or any other clinically significant haematological abnormality as judged by the investigator.
• Any clinically important abnormalities in clinical chemistry, haematology, coagulation, or urinalysis results other than those specifically described as exclusion criteria herein, as judged by the investigator.
• Systolic BP > 160 mmHg or diastolic BP > 100mmHg or HR < 50 bpm or > 100 bpm at screening. Patients taking anti-hypertensive medication should be on a stable treatment regimen of antihypertensive therapy for at least 30 days prior to the screening visit.
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, as considered by the investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
• Kidney cyst interventions such as cyst aspiration or cyst fenestration within 12 weeks prior to screening and during the screening period, or such interventions planned or anticipated within the follow-up period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - Cohort A1; Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.	Drug: AZD1613 - Part A; Part A - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.; Drug: Placebo - Part A; Part A - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.
Experimental: Part A - Cohort A2; Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.	Drug: AZD1613 - Part A; Part A - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.; Drug: Placebo - Part A; Part A - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.
Experimental: Part B - Chinese Cohort; Participants will receive 4 doses of AZD1613 or placebo on days 1, 29, 57 and 85.	Drug: AZD1613 - Part A; Part A - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.; Drug: AZD1613 - Part B; Part B - Participants will be administered doses of AZD1613 on days 1, 29, 57, and 85 according to randomization in IRT.; Drug: Placebo - Part B; Part B - Participants will be administered doses of placebo on days 1, 29, 57, and 85 according to randomization in IRT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Number of participants with at least one TEAE and SAE, including events leading to discontinuation or death; coded by system organ class and preferred term. Unit: participants.	From randomization (Day 1) through end of follow-up (up to Day 189 ±3 days)
Change From Baseline in Safety 12-Lead ECG QTcF	Change from baseline in QT interval corrected using Fridericia's formula (QTcF) measured on single 12-lead safety ECGs. Unit: milliseconds (ms).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Safety 12-Lead ECG PR Interval	Change from baseline in PR interval measured on single 12-lead safety ECGs. Unit: milliseconds (ms).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Safety 12-Lead ECG QRS Duration	Change from baseline in QRS duration measured on single 12-lead safety ECGs. Unit: milliseconds (ms).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Heart Rate (12-Lead Safety ECG)	Change from baseline in heart rate measured on single 12-lead safety ECGs. Unit: beats per minute (bpm).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in ALT	Change from baseline in alanine aminotransferase. Unit: U/L.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in AST	Change from baseline in aspartate aminotransferase. Unit: U/L.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Total Bilirubin	Change from baseline in total bilirubin. Unit: mg/dL.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Serum Creatinine	Change from baseline in serum creatinine. Unit: mg/dL.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR; CKD-EPI 2021)	Change from baseline in eGFR calculated using CKD-EPI 2021. Unit: mL/min/1.73 m².	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in INR	Change from baseline in international normalized ratio- (INR). Unit: unitless.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Prothrombin Time (PT)	Change from baseline in prothrombin time. Unit: seconds (s).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Activated Partial Thromboplastin Time (aPTT)	Change from baseline in aPTT. Unit: seconds (s).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR)	Change from baseline in UACR (geometric mean of triplicates at each visit). Unit: mg/g.	Baseline (Day -1) and scheduled visits through Day 189 ±3 days; UACR as triplicate first-morning voids per visit
Change From Baseline in Systolic Blood Pressure	Change from baseline in supine systolic blood pressure. Unit: mmHg.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Diastolic Blood Pressure	Change from baseline in supine diastolic blood pressure. Unit: mmHg.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Heart Rate (Vital Signs)	Change from baseline in supine heart rate. Unit: bpm.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Body Temperature	Change from baseline in oral body temperature. Unit: °C.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Respiratory Rate	Change from baseline in respiratory rate. Unit: breaths per minute.	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days
Change From Baseline in Oxygen Saturation (SpO2)	Change from baseline in pulse oximetry oxygen saturation. Unit: percent (%).	Baseline (Day -1) and post-dose at scheduled visits through Day 189 ±3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of AZD1613	Maximum observed serum concentration following subcutaneous or intravenous administration. Unit: µg/mL.	Intensive PK sampling from Day 1 through Day 189 per protocol schedule
Area Under the Concentration-Time Curve to Last Quantifiable Concentration (AUClast) of AZD1613	AUC from time zero to last quantifiable concentration. Unit: h·µg/mL (or day·µg/mL; align with bioanalytical report).	Intensive PK sampling from Day 1 through Day 189 per protocol schedule
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of AZD1613	AUC from time zero extrapolated to infinity. Unit: h·µg/mL (or day·µg/mL).	Intensive PK sampling from Day 1 through Day 189 per protocol schedule
Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau) of AZD1613	AUC over the dosing interval at steady state. Unit: h·µg/mL (or day·µg/mL).	Over the dosing interval (τ = 28 days) at steady state; sampling through Day 189
Time to Maximum Observed Serum Concentration (Tmax) of AZD1613	Time to reach Cmax after dosing. Unit: hours (h).	Intensive PK sampling from Day 1 through Day 189 per protocol schedule
Terminal Elimination Half-Life (t½) of AZD1613	Half-life associated with terminal slope (λz) of the concentration-time curve. Unit: hours (h) or days (d).	Intensive PK sampling from Day 1 through Day 189 per protocol schedule
Incidence of Anti-Drug Antibodies (ADA) to AZD1613	Number of participants with ADA-positive response based on validated tiered assay (screen and confirm). Unit: participants.	Predose on dosing days and during follow-up through Day 189 ±3 days
ADA Titer to AZD1613	Titer among confirmed ADA-positive samples. Unit: reciprocal dilution (titer).	Predose on dosing days and during follow-up through Day 189 ±3 days
Change From Baseline in PD Markers of PAPPA-1 Inhibition	Change from baseline in pharmacodynamic marker of PAPPA-1 inhibition. Unit: ng/mL (or assay-specific unit).	Baseline to scheduled post-dose time points through Day 189 ±3 days

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2025
• Primary Completion (Estimated): January 4, 2027
• Study Completion (Estimated): January 4, 2027

Study Registration Dates

• First Submitted: October 23, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 14, 2025

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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: D9050C00002; Identifier Number (Registry Identifier: 174499)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No