Safety and Tolerability Study of XXB750 in Heart Failure Participants With Reduced or Mildly Reduced Ejection Fraction (HFrEF/HFmrEF)

NCT ID: NCT05328752

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-17
• Study Completion Date: 2024-01-18

Brief Summary

This is a multi-center, randomized, sponsor open-label, participant- and investigator-blinded, placebo-controlled, single and multiple dose study to investigate the safety and tolerability of XXB750 in HFrEF/HFmrEF.

Detailed Description

A screening period of up to 29 days will be used to assess participants' eligibility. This study will consist of 2 cohorts. Cohort 1 will include participants on stable therapies of ACEi/ARB and beta-blockers, in addition to other standard of care medications. Cohort 2 will consist of participants treated with sacubitril/valsartan and beta-blockers, in addition to other standard of care medications.

For Cohort 1 participants will be randomized in a 2:1 ratio to receive a single dose of subcutaneous (s.c) XXB750 or placebo. For Cohort 2, participants will be randomized in a 3:1 ratio to receive three doses of either s.c. XXB750 or placebo.

Cohort 1: After an initial domiciling period following study drug administration, participants will be followed for 13 weeks post-dosing for safety, tolerability and PK until the End of Study visit on Day 91.

Cohort 2: After a domiciling period following first study drug administration of XXB750 or placebo, participants will be followed for 27 days post dosing for safety, tolerability and PK. On Day 28, participants will be re domiciled and receive a second dose of either XXB750 or placebo. Participants will be followed for another 27 days post-dosing for safety and tolerability. On Day 56, participants will be re-domiciled and receive a third dose of either XXB750 or placebo. After the third domiciling period, participants will be followed for 13 weeks post-dosing for safety, tolerability and PK until the End of Study visit on Day 146.

Conditions

Heart Failure With Reduced Ejection Fraction (HFrEF); or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

XXB750 Cohort 1

XXB750, single dose

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

XXB750

Placebo Cohort 1

Placebo, single dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

XXB750 Cohort 2

XXB750, multiple doses

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

XXB750

Placebo Cohort 2

Placebo, multiple doses

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

XXB750

XXB750

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• NYHA functional class II-III
• LVEF ≤ 50% documented at screening
• Systolic blood pressure 110 - 160 mmHg (cohort 1) or 105-160 mmHg (cohort 2), and heart rate between 50-90 beats per minute, inclusive
• Treatment with a stable dose of a beta blocker.
• Cohort 1: Treatment with a stable dose of ACE inhibitor or ARB
• Cohort 2: Treatment with a stable dose of sacubitril/valsartan.

Exclusion Criteria

• Acute decompensated heart failure within 3 months prior to screening. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
• Hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation at screening
• Implantation of a CRT device within 3 months prior to screening or intent to implant a CRT during the study period
• History of severe pulmonary disease (e.g. COPD) requiring chronic supplemental oxygen therapy or pulmonary hypertension requiring pharmacology treatment at Screening
• eGFR <45 mL/min/1.73 m2 at screening
• Cohort 1 only: Treatment with sacubitril/valsartan currently or within 4 weeks from screening
• Cohort 2: Treatment with ACE inhibitor or ARB currently or within 4 weeks from screening
• BMI >40 kg/m2

Other protocol-specific criteria may apply.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Nature Coast Clinical Research LLC

Inverness, Florida, United States

Jacksonville Ctr for Clin Rea Main Centre

Jacksonville, Florida, United States

Fairview Health Services .

Saint Paul, Minnesota, United States

Novartis Investigative Site

Groningen, , Netherlands

Countries

United States; Netherlands

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18250

Results for CXXB750A12101 from the Novartis Clinical Trials Website

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2455

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

2021-006683-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CXXB750A12101

Identifier Type: -

Identifier Source: org_study_id