Clinical trial NCT05328752: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, placebo-controlled safety study of XXB750
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
Secondary outcomes:
measure: Pharmacokinetics parameters Tmax
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
measure: Pharmacokinetics parameters Cmax
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
measure: Pharmacokinetics parameters AUClast for Cohort 1
timeFrame: 91 days
measure: Pharmacokinetics parameters AUCinf for Cohort 1
timeFrame: 91 days
measure: Pharmacokinetics parameters Vz/F
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
measure: Pharmacokinetics parameters CL/F
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
measure: Pharmacokinetics parameters T1/2
timeFrame: 91 days (Cohort 1), 146 days (Cohort 2)
measure: Pharmacokinetics parameters AUCtau for Cohort 2
timeFrame: 146 days
Other outcomes:
Locations:
city: Inverness
country: United States
facility: Nature Coast Clinical Research LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Ctr for Clin Rea Main Centre
state: Florida
city: Saint Paul
country: United States
facility: Fairview Health Services .
state: Minnesota
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: