Heart Failure With Reduced Ejection Fraction (HFrEF)Phase 1NCT05328752
Safety and Tolerability Study of XXB750 in Heart Failure Participants With Reduced or Mildly Reduced Ejection Fraction (HFrEF/HFmrEF)
A Phase 1 study testing XXB750 in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF), run by Novartis Pharmaceuticals at 4 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction (HFrEF), or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)
- What is being tested?
- XXB750
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 17 May 2022to 18 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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 locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Nature Coast Clinical Research LLC
Inverness, Florida, 34452
Jacksonville Ctr for Clin Rea Main Centre
Jacksonville, Florida, 32216
Fairview Health Services .
Saint Paul, Minnesota, 55102
About this study
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)
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.
Read the 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.
- Conditions
- Heart Failure With Reduced Ejection Fraction (HFrEF), or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)
- Being tested
- XXB750, Placebo
- Keywords
- heart failure, reduced ejection fraction, mildly reduced ejection fraction, HFrEF, HFmrEF, XXB750
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XXB750Drug
XXB750
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| XXB750 Cohort 1 | Experimental | XXB750, single dose Receives: Drug: XXB750 |
| Placebo Cohort 1 | Placebo comparator | Placebo, single dose Receives: Drug: Placebo |
| XXB750 Cohort 2 | Experimental | XXB750, multiple doses Receives: Drug: XXB750 |
| Placebo Cohort 2 | Placebo comparator | Placebo, multiple doses Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 91 days (Cohort 1), 146 days (Cohort 2)
Secondary outcomes (8)
Pharmacokinetics parameters Tmax
To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) parameters of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 91 days
Pharmacokinetics parameters Vz/F
To evaluate the pharmacokinetics parameters: Vd/F of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Measured: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters CL/F
To evaluate the pharmacokinetics parameters: (CL/F) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Measured: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters T1/2
To evaluate the pharmacokinetics parameters: (T1/2) of XXB750 in adult participants with chronic stable HFrEF/HFmrEF.
Measured: 91 days (Cohort 1), 146 days (Cohort 2)
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.
Measured: 146 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2022
- Study start17 May 2022
- Primary completion18 Jan 2024
- Study completion18 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, placebo-controlled safety study of XXB750
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05328752
- Sponsor's protocol ID
- CXXB750A12101
- Other IDs
- 2021-006683-24
- Status last verified
- Sep 2025
- First submitted
- 30 Mar 2022
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05328752
- Acronym / sponsor ID
- CXXB750A12101
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 May 2022 (actual)
- Primary completion
- 18 Jan 2024 (actual)
- Study completion
- 18 Jan 2024 (actual)
- First posted
- 14 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
- Model description
- randomized, placebo-controlled safety study of XXB750
| Arm | Type | Receives |
|---|---|---|
| XXB750 Cohort 1 | Experimental | Drug: XXB750XXB750, single dose |
| Placebo Cohort 1 | Placebo comparator | Drug: PlaceboPlacebo, single dose |
| XXB750 Cohort 2 | Experimental | Drug: XXB750XXB750, multiple doses |
| Placebo Cohort 2 | Placebo comparator | Drug: PlaceboPlacebo, multiple doses |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XXB750XXB750 | Drug | XXB750 Cohort 1, XXB750 Cohort 2 |
| PlaceboPlacebo | Drug | Placebo Cohort 1, Placebo Cohort 2 |
Primary outcome
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
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
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).
8 secondary outcomes
Pharmacokinetics parameters Tmax
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters Cmax
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters AUClast for Cohort 1
Time frame: 91 days
Pharmacokinetics parameters AUCinf for Cohort 1
Time frame: 91 days
Pharmacokinetics parameters Vz/F
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters CL/F
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters T1/2
Time frame: 91 days (Cohort 1), 146 days (Cohort 2)
Pharmacokinetics parameters AUCtau for Cohort 2
Time frame: 146 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2025.
- Results for CXXB750A12101 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XXB750 in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and or Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF), run by Novartis Pharmaceuticals at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 91 days (Cohort 1), 146 days (Cohort 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.