A Study to Evaluate CIN-107 for the Treatment of Patients With Uncontrolled Hypertension and Chronic Kidney Disease

Phase 2

Completed

Conditions: Chronic Kidney Diseases
Uncontrolled Hypertension

Interventions: Drug: CIN-107
Drug: Placebo

Registration Number: NCT05432167

Lead Sponsor: AstraZeneca

Brief Summary: This study will evaluate the efficacy and safety of CIN-107 for the treatment of hypertension in patients with uncontrolled hypertension (uHTN) and Chronic Kidney Disease (CKD).

Detailed Description: This randomized, double-blind, placebo-controlled will evaluate the efficacy and safety of CIN-107 in patients with uHTN and CKD. Approximately 200 patients will be randomized in a 1:1:1 ratio into 1 of the 3 treatment groups (placebo, low dose treatment strategy and high dose treatment strategy).

The study will consist of the following 3 periods:

* A Screening Period of up to 5 weeks;

* A Double-Blind Treatment Period of 26 weeks; and

* A Follow-Up Period of 2 weeks.

Patients will complete the study in approximately 8 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 195

Inclusion Criteria

Has a mean seated SBP ≥ 140 mmHg.
Has a prior diagnosis of mild-to-severe CKD.
Has an elevated UACR.
Is currently taking an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) at the maximum tolerated daily dose.

Exclusion Criteria

Have a documented diagnosis of type 1 diabetes.
Are not willing or not able to discontinue a mineralocorticoid receptor antagonist (MRA) or a potassium sparing diuretic as part of an existing antihypertensive regimen.
Have a single occurrence of mean seated SBP >180 mmHg or DBP >110 mmHg during the Screening Period.
Has a body mass index (BMI) >50 kg/m^2.
Has documented bilateral clinically relevant renal artery stenosis of ≥70%.
Has had dialysis for acute kidney injury/acute renal failure within 12 weeks prior to the Screening Period or has a planned dialysis or kidney transplantation during the course of the study.
Has known documented chronic heart failure New York Heart Association Class III or Class IV and/or hospitalization for heart failure within 6 months of Screening.
Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months of Screening.
Has known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease.
Has planned any major cardiac surgery during the study or had major cardiac surgery within 6 months of Screening.
Has had a prior solid organ transplant or cell transplant.
Has a known hypersensitivity to CIN-107 or drugs of the same class
Has received immunotherapy for treatment of CKD within 6 months of Screening.
Has any clinically relevant medical or surgical conditions including unstable conditions and/or conditions requiring regular transfusion or treatment with systemic immunosuppressants, including corticosteroids.
Serum potassium <3.5 mEq/L or >5.0 mEq/L
Serum sodium <135 mEq/L
Serum aspartate aminotransferase or alanine aminotransferase >3 × upper limit of normal (ULN); or Total bilirubin >2 × ULN, unless due to Gilbert's syndrome.
GFR is < 25 or > 75 mL/min/1.73 m2
Has uncontrolled diabetes with glycosylated hemoglobin >10.5%.
Is positive for Human immunodeficiency disease (HIV) antibody, hepatitis B surface antigen, or hepatitis C virus Ribonucleic acid (RNA).
Has typical consumption of >14 alcoholic drinks weekly.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose CIN-107	CIN-107	Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks.
Placebo	Placebo	Patients will take oral tablets of Placebo for 26 weeks. The dose strength may be titrated within 6 weeks.
Low dose CIN-107	CIN-107	Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo	At Week 26	Mean change in seated SBP from baseline to Week 26 of pooled CIN-107 and placebo was assessed.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group	At Week 26	Mean change in seated SBP from baseline to Week 26 of high-dose CIN-107 dosing group and placebo was assessed.
Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group	At Week 26	The mean change in seated SBP from baseline to Week 26 of low-dose CIN-107 dosing group and placebo was assessed.