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

September 24, 2025 updated by: Novartis Pharmaceuticals

A Randomized, Participant- and Investigator-blinded, Sponsor Open-label, Placebo-controlled, Single and Multiple Dose Study to Investigate the Safety and Tolerability of XXB750 in Heart Failure Participants With Reduced or Mildly Reduced Ejection Fraction (HFrEF/HFmrEF)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
  • United States
    • Florida
      • Inverness, Florida, United States, 34452
        • Nature Coast Clinical Research LLC
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Ctr for Clin Rea Main Centre
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • Fairview Health Services .

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key 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.

Key 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XXB750 Cohort 1
XXB750, single dose
Drug: XXB750
XXB750
Placebo Comparator: Placebo Cohort 1
Placebo, single dose
Drug: Placebo
Placebo
Experimental: XXB750 Cohort 2
XXB750, multiple doses
Drug: XXB750
XXB750
Placebo Comparator: Placebo Cohort 2
Placebo, multiple doses
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events, which may include abnormal vital signs, safety lab tests, or ECG parameters that induce clinical signs or symptoms, are considered clinically significant or require therapy
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the safety and tolerability of XXB750 in adult participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).
91 days (Cohort 1), 146 days (Cohort 2)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics parameters Tmax
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) parameters of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters Cmax
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the pharmacokinetics parameters: Peak plasma concentration (Cmax) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters AUClast for Cohort 1
Time Frame: 91 days
To evaluate the pharmacokinetics parameters: Area under the plasma concentration curve (AUClast) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days
Pharmacokinetics parameters AUCinf for Cohort 1
Time Frame: 91 days
To evaluate the pharmacokinetics parameters: Area under the curve (AUCinf) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days
Pharmacokinetics parameters Vz/F
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the pharmacokinetics parameters: Vd/F of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters CL/F
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the pharmacokinetics parameters: (CL/F) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters T1/2
Time Frame: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the pharmacokinetics parameters: (T1/2) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters AUCtau for Cohort 2
Time Frame: 146 days
To evaluate the pharmacokinetics parameters: Area under the curve (AUCtau) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
146 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2022

Primary Completion (Actual)

January 18, 2024

Study Completion (Actual)

January 18, 2024

Study Registration Dates

First Submitted

March 30, 2022

First Submitted That Met QC Criteria

April 13, 2022

First Posted (Actual)

April 14, 2022

Study Record Updates

Last Update Posted (Estimated)

September 30, 2025

Last Update Submitted That Met QC Criteria

September 24, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CXXB750A12101
  • 2021-006683-24 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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