A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease.

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease

The purpose of this study is to evaluate the safety, tolerability and the pharmacodynamics (PD) of AZD4144 following oral administration in participants with atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Drug: AZD4144; Other: Placebo

Detailed Description

This is a Phase 1b, randomized, double blind, placebo-controlled study and will be conducted in participants with established ASCVD and CKD with persistent inflammation (High-sensitivity C-reactive protein [hsCRP] > 2 mg/L and eGlomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73m2). The participants will be randomized in the 1:1 ratio to either receive treatment with AZD4144 or placebo.

The study will be comprised of:

• A screening period of 28 days
• Treatment period where each participant will either receive oral dose of AZD4144 or placebo for 28 days.
• A follow-up visit (Day 35 ±1) and a Final Follow-up (on Day 56±1) post first dose administration.

The total duration of the study will be approximately 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Research Site
  • Sofia, Bulgaria, 1527
    • Research Site
• Hungary
  • Gyöngyös, Hungary, 3200
    • Research Site
  • Kistarcsa, Hungary, 2143
    • Research Site
• Romania
  • Bucharest, Romania, 11658
    • Research Site
  • Cluj-Napoca, Romania, 400006
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91203
      • Research Site
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami, Florida, United States, 33125
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
    • Tampa, Florida, United States, 33603
      • Research Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Research Site
  • New York
    • The Bronx, New York, United States, 10455
      • Research Site
  • Texas
    • Sherman, Texas, United States, 75092
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Participants with established ASCVD history of one or more of the following

  1. Prior Myocardial infarction (MI) (>60 days from index event) or coronary revascularization procedure like coronary stenting or Coronary artery bypass graft (CABG)
  2. Prior ischemic stroke (>60 days from index event)
  3. Symptomatic Peripheral Arterial Disease
• Chronic kidney disease defined as eGlomular filtration rate (eGFR) ≥ 30 to < 60 mL/min/1.73 m2
• Serum hsCRP > 2 mg/L
• Body mass index ≥ 18 to ≤ 45 kg/m2

• All females must have a negative pregnancy test at the Screening Visit and at the randomization visit

  1. Sexually active male participants with partner of childbearing potential must adhere to the contraception methods
  2. Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception
  3. Females of non-childbearing potential must be confirmed at the Screening visit

Key Exclusion Criteria:

• History of malignancy within the last 5 years
• History of MI, coronary revascularization, stroke or revascularization for peripheral arterial disease in the 60 days prior to Screening
• Active systemic infection within 30 days
• Clinically significant active and chronic infections within 60 days prior to randomization
• Clinically significant recurrent infection (≥ 2× during the last 12-month period).
• Renal transplant participants, participants on dialysis, and those with a history of acute kidney injury in the past 12 month

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD4144; Participants will receive oral dose of AZD4144 for 28 days.	Drug: AZD4144; Oral solution of AZD4144 will be given to randomised participants as per the arm they have been assigned.
Placebo Comparator: Placebo; Participants will receive oral dose of Placebo for 28 days.	Other: Placebo; Placebo will be given orally to randomized participants as per the arm they are assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	The safety and the tolerability of AZD4144 compared with placebo will be evaluated.	From first dose (Day 1) until Follow-up (Day 56±1)
Relative change from baseline to 4 weeks in systemic Interleukin-6 (IL-6) levels	The effect of AZD4144 on circulating inflammatory biomarker IL-6 compared with placebo will be evaluated.	Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change from baseline to 4 weeks in systemic IL-18 and High-sensitivity C-reactive protein (hsCRP) levels	The effect of AZD4144 on circulating inflammatory biomarkers IL-18 and hsCRP compared with placebo will be evaluated.	Day 1 to Day 28
Maximum plasma drug concentration (Cmax)	The Cmax after administration of AZD4144 in participants with ASCVD and CKD will be evaluated.	Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)
Time to reach maximum observed concentration (tmax)	The tmax after administration of AZD4144 in participants with ASCVD and CKD will be evaluated.	Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)
Observed lowest concentration before the next dose is administered (Ctrough)	The Ctrough after administration of AZD4144 in participants with ASCVD and CKD will be evaluated.	Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Actual): October 27, 2025
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 5, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: inflammatory cytokines; Estimated glomerular filtration rate; Cardiorenal disease; Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) cryopyrin
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; Atherosclerosis
• Other Study ID Numbers: D9441C00001; 2024-516840-24-00 (Registry Identifier: EU-CT Number)

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. 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 Pharma Data Sharing Principles. For details of our timelines, please refer 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 environmentVivli.org. A 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