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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: CIN-107

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Saraland, Alabama, United States, 36571
      • Research Site
  • California
    • Huntington Park, California, United States, 90255
      • Research Site
    • Lincoln, California, United States, 95648
      • Research Site
    • Los Angeles, California, United States, 90057
      • Research Site
    • Northridge, California, United States, 91324
      • Research Site
    • Oceanside, California, United States, 92056
      • Research Site
    • Panorama City, California, United States, 91402
      • Research Site
    • Van Nuys, California, United States, 91405
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research Site
    • Doral, Florida, United States, 33166
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Hollywood, Florida, United States, 33024
      • Research Site
    • Lake Worth, Florida, United States, 33467
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Pembroke Pines, Florida, United States, 33027
      • Research Site
    • Winter Haven, Florida, United States, 33880
      • Research Site
  • Illinois
    • Addison, Illinois, United States, 60101
      • Research Site
    • Chicago, Illinois, United States, 60607
      • Research Site
    • Morton, Illinois, United States, 61550
      • Research Site
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Research Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • Research Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11235
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Research Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Research Site
  • Texas
    • Austin, Texas, United States, 78705
      • Research Site
    • Carrollton, Texas, United States, 75006
      • Research Site
    • Dallas, Texas, United States, 75234
      • Research Site
    • Georgetown, Texas, United States, 78628
      • Research Site
    • Houston, Texas, United States, 77040
      • Research Site
    • Lampasas, Texas, United States, 76550
      • Research Site
    • San Antonio, Texas, United States, 78209
      • Research Site
  • Utah
    • West Valley City, Utah, United States, 84120
      • Research Site
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have completed Part 1 or Part 2 of Study CIN-107-124;
2. Have had acceptable safety and tolerability during Study CIN-107-124 as determined by the Investigator or Medical Monitor;
3. Have demonstrated ≥70% and ≤120% adherence to their single background antihypertensive agent and the CIN-107 placebo during Study CIN-107-124;

4. 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.
5. Are able and willing to give informed consent for participation in the clinical study.

Exclusion Criteria:

1. 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;
2. 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;
3. 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;
4. 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;
5. 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;
6. 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;
7. Have experienced a de novo or reactivated serious viral infection such as hepatitis B, hepatitis C, or HIV during Study CIN-107-124;
8. Have had any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during Study CIN-107-124;
9. 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;
10. Have anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after enrollment (Visit 1);
11. Are expected to receive or are receiving any of the exclusionary drugs (strong cytochrome P450 3A inducers);
12. 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;
13. Have been diagnosed with New York Heart Association stage III or IV chronic heart failure during Study CIN-107-124;
14. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure during Study CIN-107-124;
15. 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;
16. Have a planned coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) or any major surgical procedure;
17. Have had a CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI during Study CIN-107-124;
18. Have a planned dialysis or kidney transplant during the course of this study;
19. Have a known hypersensitivity to CIN-107 or drugs of the same class, or any of its excipients;
20. 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;
21. Are pregnant, breastfeeding, or planning to become pregnant during the study; or
22. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental 2 mg CIN-107 tablets QD; 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; 2 mg of CIN-107, once a day for 52 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2022
• Primary Completion (Actual): November 7, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CIN-107-130; D6971C00001 (Other Identifier: AstraZeneca)

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 Vivli.org. 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 approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA 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 environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No