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

Novartis Pharmaceuticals27 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

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

Interventions

XXB750DRUG

XXB750

PlaceboDRUG

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (4)

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

Outcomes

Primary Outcomes

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

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).

Time frame: 91 days (Cohort 1), 146 days (Cohort 2)

Secondary Outcomes

Pharmacokinetics parameters Tmax

To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) parameters of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.

Time frame: 91 days (Cohort 1), 146 days (Cohort 2)

Pharmacokinetics parameters Cmax

To evaluate the pharmacokinetics parameters: Peak plasma concentration (Cmax) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.

Time frame: 91 days (Cohort 1), 146 days (Cohort 2)

Pharmacokinetics parameters AUClast for Cohort 1

To evaluate the pharmacokinetics parameters: Area under the plasma concentration curve (AUClast) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.

Time frame: 91 days

Pharmacokinetics parameters AUCinf for Cohort 1

To evaluate the pharmacokinetics parameters: Area under the curve (AUCinf) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.

Time frame: 91 days

Pharmacokinetics parameters Vz/F

To evaluate the pharmacokinetics parameters: Vd/F of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.

Time frame: 91 days (Cohort 1), 146 days (Cohort 2)

Data from ClinicalTrials.gov

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