A Study of CIN-107 in Adults With Primary Aldosteronism

A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Effectiveness of CIN-107 for the Management of Blood Pressure in Patients With Primary Aldosteronism

This is a multicenter, open-label study in adult patients with PA to evaluate the effectiveness and safety of CIN-107 after up to 12 weeks of treatment (Part 1), and then for eligible, consenting patients follow patients in Part 2 for up to 74 weeks for evidence of long-term safety and tolerability.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Aldosteronism; Hyperaldosteronism
• Intervention / Treatment: Drug: CIN-107 2 mg dosing; Drug: CIN-107 4 mg dosing; Drug: CIN-107 8 mg dosing

Detailed Description

For patients in Part 1 only :

The treatment duration for patients who complete all 3 dose levels, and who opt not to continue in the extension part of the study, is 12 weeks. For patients who do not complete up-titration, the treatment duration will include at least 4 weeks of dosing with the final dose level. If down-titration of CIN-107 dose is determined at Visit 6 (Week 9), the total treatment duration may be extended to 13 weeks to allow sufficient time for CIN-107 treatment effect at the final dose to be assessed. If the final dose of CIN-107 is reached before week 8 (Visit 5) and no up-titration occurs at Visit 5, the patients will be encouraged to continue CIN-107 treatment till Visit 7 for a total of 12 weeks of treatment. The patients who opt not to continue to Part 2 will not receive any study drug and will return for their safety follow up visit (Visit 8) in 2 weeks.

For patients who opt to continue in the extension part (Part 2) of the study:

Patients will continue to receive their dose of baxdrostat and be instructed to measure BP at least once every week prior to dosing with CIN-107 in the morning, during the extension phase. Safety surveillance will be conducted if clinically indicated. Repeat and unscheduled testing for serum potassium may be measured at the investigator's clinical site or at local laboratory for a faster turn-around time to allow clinical assessment. These patients entering part 2 will skip Visit 8 and their next visit will be Visit 9.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: CinCor Pharma Clinical Trials Contact; Phone Number: 617-675-8126; Email: info@cincor.com

Study Locations

• United States
  • California
    • Greenbrae, California, United States, 94904
      • Research Site
    • San Francisco, California, United States, 94110
      • Research Site
    • West Hollywood, California, United States, 90048
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Research Site
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390-9047
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Have been diagnosed with PA.
2. Are taking mineralocorticoid receptor antagonist (MRA) to control BP; or are newly diagnosed with PA and have not started MRA treatment.
3. Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA.
4. Are willing to be compliant with the contraception and reproduction restrictions of the study.
5. Have increased SBP by ≥ 20 mmHg or have SBP ≥ 160 mmHg after dosing of MRA treatment is ceased for up to 4 weeks duration, or have SBP ≥ 150 mmHg for patients who are newly diagnosed with PA and have not taken an MRA in the past 12 weeks.

Exclusion Criteria:

1. At Screening Visit, have a single occurrence of mean seated SBP > 180 mmHg or DBP > 110 mmHg if not taking an MRA; or have a mean seated SBP ≥ 160 mmHg or DBP ≥ 100 mmHg if currently taking an MRA.
2. Have a body mass index > 45 kg/m2.
3. Have had a previous surgical intervention for an adrenal adenoma or have a planned adrenal carcinoma, adrenalectomy, renal nerve denervation, or adrenal ablative procedure during the course of the study.
4. Have a documented estimated glomerular filtration rate < 45 mL/min/1.73 m2.
5. Have a planned dialysis, kidney transplantation or any major surgical procedure during the course of the study.
6. Have known documented New York Heart Association class III or IV chronic heart failure.
7. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit.
8. Have known current severe left ventricular outflow obstruction.
9. Have had major cardiac surgery within 6 months before the Screening Visit.
10. Have a history of, or currently experiencing, clinically significant arrhythmias.
11. Have had a prior solid organ transplant or cell transplant.
12. Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen.
13. Have typical consumption of > 14 alcoholic drinks weekly.

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: CIN-107 for dosing at 2, 4, or 8 mg (QD); Patients will be provided with an initial dose of CIN-107 and start once daily (QD) dosing of CIN-107 tablets at 2 mg. At Visit 4, CIN-107 dose may be up-titrated to 4 mg QD if the patient has tolerated dosing of CIN-107 at 2 mg and the blood pressure (BP) records indicate minimal hypotension risk. At Visit 5, CIN-107 dose may be up-titrated to 8 mg QD if the patient has tolerated dosing of CIN-107 at 4 mg.

Drug: CIN-107 2 mg dosing; One tablet of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 2 mg.; Drug: CIN-107 4 mg dosing; Two tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 4 mg.; Drug: CIN-107 8 mg dosing; Four tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 8 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of CIN-107	Outcome measure is overall safety with is a composite of the following individual parameters (unit of measure in brackets): Adverse Events [number of events];; ECGs [PR interval (msec), RR interval (msec), or QTcF interval (msec); clinically significant ECG findings that are detected during the study will be reported as adverse events];; Clinical laboratory evaluations including standard safety chemistry panel, hematology, coagulation, and urinalysis [clinically significant abnormal laboratory findings that are detected during the study will be reported as adverse events];; Vital signs [pulse, temperature, heart rate and blood pressure] and physical examination data changes noted as clinically significant abnormalities that arise during the study will be recorded as adverse events	74 Weeks
Change in mean seated systolic blood pressure (SBP)	Effectiveness measured by change in mean seated SBP after 12 weeks of treatment in patients with PA	after 12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean diastolic blood pressure (DBP)	Comparison of changes in mean SBP after 12 weeks of treatment in patients with PA.	after 12 weeks of treatment
The percentage of patients achieving a seated blood pressure (BP) response <140/90 mmHg	The percent of patients who achieved a seated BP response <140/90 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.	at Week 12
The percentage of patients achieving a seated BP response <130/80 mmHg	The percent of patients who achieved a seated BP response <130/80 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.	at Week 12
The percentage of patients achieving either: - a plasma aldosterone concentration (PAC) < 15 ng/dL and a plasma renin activity (PRA) ≥ 0.5 ng/mL/h; or - an ARR < 15; or - unsuppressed renin activity PRA ≥ 1.0 ng/mL/h		after 12 weeks of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Estimated): October 10, 2024
• Study Completion (Estimated): October 10, 2024

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Primary Aldosteronism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hyperaldosteronism
• Other Study ID Numbers: CIN-107-122; D6970C00001 (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