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

Heart Failure With Reduced Ejection Fraction (HFrEF) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05328752
• Other study ID #: CXXB750A12101
• Secondary ID: 2021-006683-24
• Status: Completed
• Phase: Phase 1
• Start date: May 17, 2022
• Est. completion date: January 18, 2024

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 18, 2024
• Est. primary completion date: January 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction (HFrEF)

Intervention

Drug:
• XXB750
XXB750
• Placebo
Placebo

Locations

Country	Name	City	State
Netherlands	Novartis Investigative Site	Groningen
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	91 days (Cohort 1), 146 days (Cohort 2)
Secondary	Pharmacokinetics parameters Tmax	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)
Secondary	Pharmacokinetics parameters Cmax	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)
Secondary	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.	91 days
Secondary	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.	91 days
Secondary	Pharmacokinetics parameters Vz/F	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)
Secondary	Pharmacokinetics parameters CL/F	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)
Secondary	Pharmacokinetics parameters T1/2	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)
Secondary	Pharmacokinetics parameters AUCtau for Cohort 2	To evaluate the pharmacokinetics parameters: Area under the curve (AUCtau) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.	146 days