search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
XXB750
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction (HFrEF) focused on measuring heart failure, reduced ejection fraction, mildly reduced ejection fraction, HFrEF, HFmrEF, XXB750

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • NYHA functional class II-III
  • LVEF ≤ 45% documented at screening
  • Systolic blood pressure 110 - 180 mmHg (cohort 1) or 105-180 mmHg (cohort 2), and heart rate ≤90 beats per minute
  • 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 heart failure, 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 2 weeks from screening
  • Cohort 2: Treatment with ACE inhibitor or ARB currently or within 4 weeks from screening
  • BMI >35 kg/m2

Other protocol-specific criteria may apply.

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

XXB750 Cohort 1

Placebo Cohort 1

XXB750 Cohort 2

Placebo Cohort 2

Arm Description

XXB750, single dose

Placebo, single dose

XXB750, multiple doses

Placebo, multiple doses

Outcomes

Primary Outcome Measures

Number of participants experiencing Adverse Events, SAEs (if applicable)
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).
Number of participants with abnormal vital signs, safety lab tests and ECG parameters
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).

Secondary Outcome Measures

Pharmacokinetics parameters Tmax
To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) parameters of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Pharmacokinetics parameters Cmax
To evaluate the pharmacokinetics parameters: Peak plasma concentration (Cmax) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
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.
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.
Pharmacokinetics parameters Vz/F
To evaluate the pharmacokinetics parameters: Vd/F of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Pharmacokinetics parameters CL/F
To evaluate the pharmacokinetics parameters: (CL/F) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Pharmacokinetics parameters T1/2
To evaluate the pharmacokinetics parameters: (T1/2) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
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.

Full Information

First Posted
March 30, 2022
Last Updated
October 23, 2023
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT05328752
Brief Title
Safety and Tolerability Study of XXB750 in Heart Failure Participants With Reduced or Mildly Reduced Ejection Fraction (HFrEF/HFmrEF)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 17, 2022 (Actual)
Primary Completion Date
January 19, 2024 (Anticipated)
Study Completion Date
January 21, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction (HFrEF), or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)
Keywords
heart failure, reduced ejection fraction, mildly reduced ejection fraction, HFrEF, HFmrEF, XXB750

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
randomized, placebo-controlled safety study of XXB750
Masking
ParticipantCare Provider
Masking Description
Site will have masked and unmasked investigators. An unmasked investigator will prepare and administer dose while a masked investigator will perform all assessments.
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
XXB750 Cohort 1
Arm Type
Experimental
Arm Description
XXB750, single dose
Arm Title
Placebo Cohort 1
Arm Type
Placebo Comparator
Arm Description
Placebo, single dose
Arm Title
XXB750 Cohort 2
Arm Type
Experimental
Arm Description
XXB750, multiple doses
Arm Title
Placebo Cohort 2
Arm Type
Placebo Comparator
Arm Description
Placebo, multiple doses
Intervention Type
Drug
Intervention Name(s)
XXB750
Intervention Description
XXB750
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Number of participants experiencing Adverse Events, SAEs (if applicable)
Description
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)
Title
Number of participants with abnormal vital signs, safety lab tests and ECG parameters
Description
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 Outcome Measure Information:
Title
Pharmacokinetics parameters Tmax
Description
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)
Title
Pharmacokinetics parameters Cmax
Description
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)
Title
Pharmacokinetics parameters AUClast for Cohort 1
Description
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
Title
Pharmacokinetics parameters AUCinf for Cohort 1
Description
To evaluate the pharmacokinetics parameters: Area under the curve (AUCinf) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Time Frame
91 days
Title
Pharmacokinetics parameters Vz/F
Description
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)
Title
Pharmacokinetics parameters CL/F
Description
To evaluate the pharmacokinetics parameters: (CL/F) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Time Frame
91 days (Cohort 1), 146 days (Cohort 2)
Title
Pharmacokinetics parameters T1/2
Description
To evaluate the pharmacokinetics parameters: (T1/2) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Time Frame
91 days (Cohort 1), 146 days (Cohort 2)
Title
Pharmacokinetics parameters AUCtau for Cohort 2
Description
To evaluate the pharmacokinetics parameters: Area under the curve (AUCtau) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Time Frame
146 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Inverness
State/Province
Florida
ZIP/Postal Code
34452
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs