Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, open-label extension (OLE) study to evaluate the long-term safety, tolerability, and effectiveness of CIN-107 for up to 52 weeks in patients with HTN who have completed Part 1 or Part 2 of Study CIN-107-124. The study will be conducted at clinical sites that have participated in the double-blind, Phase 2 Study CIN-107-124.

Official Title
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An Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124 to Evaluate the Long-Term Safety and Effectiveness of CIN-107

Conditions
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Hypertension

Intervention / Treatment
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* Drug: CIN-107


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed Part 1 or Part 2 of Study CIN-107-124; Have had acceptable safety and tolerability during Study CIN-107-124 as determined by the Investigator or Medical Monitor; Have demonstrated ≥70% and ≤120% adherence to their single background antihypertensive agent and the CIN-107 placebo during Study CIN-107-124; Agree to comply with the contraception and reproduction restrictions of the study as follows: Male patients must agree to abstain from sperm donation from Day 1 through 90 days after the final dose of study drug; Female patients of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) must have a documented negative serum pregnancy test at enrollment (Visit 1); and Female patients of childbearing potential must use a highly effective method of contraception (ie, <1% failure rate) from Day 1 through 30 days after the last administration of study drug. Are able and willing to give informed consent for participation in the clinical study. Exclusion Criteria: Have met Protocol-defined stopping criteria, were withdrawn from the study, discontinued CIN-107 at the time of Visits 6 or 9, or were not compliant with the Protocol during Study CIN-107-124; Have received treatment with any investigational agent for disease intervention (ie, other than study drug) during Study CIN-107-124, or since the last administration of study drug in Study CIN-107-124, or plans to participate in another clinical study within 30 days of discontinuation of study drug; Have had any new, significant, or uncontrolled comorbidity since initially enrolling in Study CIN-107-124 that would increase the risk of the patient in Study CIN-107-130, as determined by the Investigator; Have had a mean seated SBP ≥170 mmHg or DBP ≥105 mmHg at the end of Part 1 or Part 2 of Study CIN-107-124; Have an upper arm circumference that does not meet the cuff measurement criteria for the selected BP machine at Visit 1 of Study CIN-107-130; Have any uncontrolled or clinically significant laboratory abnormality that would affect safety, interpretation of study data, or the patient's participation in the study, as determined by the Investigator; Have experienced a de novo or reactivated serious viral infection such as hepatitis B, hepatitis C, or HIV during Study CIN-107-124; Have had any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during Study CIN-107-124; Have developed a malignancy (with the exception of non-serious local and resectable basal or squamous cell carcinoma of the skin) during Study CIN-107-124; Have anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after enrollment (Visit 1); Are expected to receive or are receiving any of the exclusionary drugs (strong cytochrome P450 3A inducers); Have known secondary causes of HTN (eg, renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, hyperparathyroidism, pheochromocytoma, Cushing's syndrome, or aortic coarctation) except obstructive sleep apnea; Have been diagnosed with New York Heart Association stage III or IV chronic heart failure during Study CIN-107-124; Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure during Study CIN-107-124; Have a known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease diagnosed from a prior echocardiogram; Have a planned coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) or any major surgical procedure; Have had a CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI during Study CIN-107-124; Have a planned dialysis or kidney transplant during the course of this study; Have a known hypersensitivity to CIN-107 or drugs of the same class, or any of its excipients; Have any clinically relevant medical or surgical conditions (including unstable conditions and/or treatment with systemic immunosuppressants including corticosteroids) that, in the opinion of the Investigator, would put the patient at risk by participating in the study; Are pregnant, breastfeeding, or planning to become pregnant during the study; or Are considered to be unsuitable for any other reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study outcomes by the Investigator, after reviewing medical and psychiatric history, physical examination, and laboratory evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Interventional Model Description: Eligible patients from Study CIN-107-124 who elect to participate in this study will continue treatment with 2 mg CIN-107 tablets QD after enrollment, starting at Visit 1 and concluding at EOT (Visit 7)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 2 mg CIN-107 tablets QD<br>Treatment with 2 mg CIN-107 tablets, by mouth, once per day. Starting at Visit 1 and concluding at EOT (Visit 7). | Drug: CIN-107<br>* 2 mg of CIN-107, once a day for 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the long-term safety and tolerability of CIN-107 | Evaluate TEAEs Evaluate treatment-emergent SAEs Evaluate TEAEs of special interest Evaluate TEAEs leading to treatment premature discontinuation Evaluate treatment-emergent marked laboratory abnormalities Evaluate the change on standing SBP and diastolic BP, measured pre-dose at the clinical site, from baseline (V1) to (EOT) Evaluate vital signs, standing BP and heart rate, physical examinations, ECGs, weight, clinical lab evaluations, including standard chemistry panel, hematology, coagulation and urinalysis | up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean systolic blood pressure (SBP) change |  | over 52 weeks | 
| Mean diastolic blood pressure (DBP) change |  | over 52 weeks | 
| Percentage of patients achieving a seated SBP <130 mmHg |  | over 52 weeks | 
| Percentage of non-responders in Study CIN-107-124 achieving a seated SBP response <130 mmHg with CIN-107 | With/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength | over 52 weeks | 
| Percentage of responders in Study CIN-107-124 maintaining a seated SBP response <130 mmHg with CIN-107 | With/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength | over 52 weeks |