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

Novartis

Status and phase: Completed; Phase 1

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

Treatments: Drug: Placebo; Drug: XXB750

Study type: Interventional

Funder types: Industry

Identifiers

NCT05328752

CXXB750A12101

2021-006683-24 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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27 participants in 4 patient groups, including a placebo group

XXB750 Cohort 1

Experimental group

Description:

XXB750, single dose

Treatment:

Drug: XXB750

Placebo Cohort 1

Placebo Comparator group

Description:

Placebo, single dose

Treatment:

Drug: Placebo

XXB750 Cohort 2

Experimental group

Description:

XXB750, multiple doses

Treatment:

Drug: XXB750

Placebo Cohort 2

Placebo Comparator group

Description:

Placebo, multiple doses

Treatment:

Drug: Placebo