Clinical trial NCT06675175: A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Kidney Disease
Atherosclerotic Cardiovascular Disease
Keywords: Cardiorenal disease
Estimated glomerular filtration rate
Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) cryopyrin
inflammatory cytokines
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-11-05
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: From first dose (Day 1) until Follow-up (Day 56±1)
measure: Relative change from baseline to 4 weeks in systemic Interleukin-6 (IL-6) levels
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Relative change from baseline to 4 weeks in systemic IL-18 and High-sensitivity C-reactive protein (hsCRP) levels
timeFrame: Day 1 to Day 28
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)
measure: Time to reach maximum observed concentration (tmax)
timeFrame: Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)
measure: Observed lowest concentration before the next dose is administered (Ctrough)
timeFrame: Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Farmington Hills
country: United States
facility: Research Site
state: Michigan
city: Bronx
country: United States
facility: Research Site
state: New York
city: Sherman
country: United States
facility: Research Site
state: Texas
city: Pleven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyöngyös
country: Hungary
facility: Research Site
city: Kistarcsa
country: Hungary
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
Study officials:
References: