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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group, Dose-Ranging Study to Evaluate CIN-107 for the Treatment of Patients With Uncontrolled Hypertension and Chronic Kidney Disease

Conditions
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Uncontrolled Hypertension, Chronic Kidney Diseases

Intervention / Treatment
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* Drug: CIN-107
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose CIN-107<br>Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks. | Drug: CIN-107<br>* Patients will take CIN-107 tablets by mouth once daily.<br>|
| Experimental: High dose CIN-107<br>Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks. | Drug: CIN-107<br>* Patients will take CIN-107 tablets by mouth once daily.<br>|
| Placebo Comparator: Placebo<br>Patients will take oral tablets of Placebo for 26 weeks. The dose strength may be titrated within 6 weeks. | Drug: Placebo<br>* Patients will take placebo tablets by mouth once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean seated systolic blood pressure (SBP) | Change in mean seated SBP from baseline to Week 26 in patients receiving CIN-107 compared to placebo. | At Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in SBP in CIN-107 compared to placebo in patients assigned to the high-dose strategy group | Change in mean seated SBP from baseline to Week 26 in patients receiving high-dose CIN-107 compared to placebo | At Week 26 | 
| Change from baseline of SBP in CIN-107 compared to placebo in patients assigned to the low-dose strategy group | Change in mean seated SBP from baseline to Week 26 in patients receiving low-dose CIN-107 compared to placebo | At Week 26 |