Heart FailurePhase 2NCT06142383
A Proof of Concept and Dose-finding Study of XXB750 in Patients With Heart Failure
A Phase 2 study testing XXB750 Low dose, XXB750 Medium Dose and XXB750 High Dose in people with Heart Failure, run by Novartis Pharmaceuticals at 62 sites in 12 countries.
Trial summary
This was a multicenter, randomized, placebo- and active-controlled, parallel-group, 24-week trial to investigate the efficacy, safety, and tolerability of XXB750 in participants with HFrEF/HFmrEF. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- XXB750 Low dose, XXB750 Medium Dose and XXB750 High Dose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 62 sitesin 12 countries
- Study dates
- 12 Dec 2023to 1 Nov 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current symptom(s) of HF NYHA class II-III and LVEF < 50%
- Elevated NT-proBNP levels at screening.
- Receiving standard of care background HF therapy.
Who cannot join
- Current acute decompensated HF or hospitalization for HF within 3 months prior to screening.
- Current symptomatic hypotension (for example dizziness/presyncope).
- K+ > 5.4 mmol/L at screening
- eGFR < 30 mL/min/1.73m2 at screening
Trial locations and contacts
62 sites in 12 countries.
62 sites in 12 countries
United States14 sites
American Clinical Trials
Acworth, Georgia, 30101
Aultman Hospital
Canton, Ohio, 44710
SEC Clinical Research
Dothan, Alabama, 36305
Anderson Medical Research
Ft. Washington, Maryland, 20744
Heart Clinic of Hammond
Hammond, Louisiana, 70403
Heart Center Research Llc
Huntsville, Alabama, 35801
Nature Coast Clinical Research LLC
Inverness, Florida, 34452
The Research Group
Lexington, Kentucky, 40503
NexGen Research
Lima, Ohio, 45801
Inpatient Research Clinical LLC
Miami Lakes, Florida, 33014
Dominion Medical Associates
Richmond, Virginia, 23219
Revival Research Institute
Troy, Michigan, 48084
Tennessee Center For Clinical Trials
Tullahoma, Tennessee, 37388
Cardiology Partners Clinical Research Institute
Wellington, Florida, 33449
Bulgaria8 sites
Novartis Investigative Site
Blagoevgrad, 270 0
Novartis Investigative Site
Gabrovo, 5300
Novartis Investigative Site
Kyustendil, 2500
Novartis Investigative Site
Pleven, 5800
Novartis Investigative Site
Plovdiv, 4002
Novartis Investigative Site
Sofia, 1233
Novartis Investigative Site
Sofia, 1510
Novartis Investigative Site
Varna, 9010
Spain8 sites
Novartis Investigative Site
Huelva, Andalusia, 21005
Novartis Investigative Site
Las Palmas GC, 35010
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Majadahonda, Madrid, 28222
Novartis Investigative Site
Málaga, 29010
Novartis Investigative Site
Santiago Compostela, A Coruna, 15706
Novartis Investigative Site
Valencia, 46010
Novartis Investigative Site
Valencia, 46026
Germany7 sites
Novartis Investigative Site
Berlin, 13347
Novartis Investigative Site
Cologne, 51065
Novartis Investigative Site
Gladbeck, 45968
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Ludwigshafen, 67067
Novartis Investigative Site
Papenburg, 26871
Novartis Investigative Site
Schwäbisch Hall, 74523
Italy7 sites
Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Messina, ME, 98125
Novartis Investigative Site
Milan, MI, 20138
Novartis Investigative Site
Pordenone, PN, 33170
Novartis Investigative Site
Roma, RM, 00133
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Trieste, TS, 34149
Slovakia6 sites
Novartis Investigative Site
Bardejov, Slovakia, 085 01
Novartis Investigative Site
Košice, Slovakia, 040 01
Novartis Investigative Site
Martin, Slovakia, 036 01
Novartis Investigative Site
Nitra, Slovakia, 949 11
Novartis Investigative Site
Prešov, Slovakia, 080 01
Novartis Investigative Site
Svidník, Slovakia, 089 01
Japan4 sites
Novartis Investigative Site
Kawasaki, Kanagawa, 216-8511
Novartis Investigative Site
Maebashi, Gunma, 371 8511
Novartis Investigative Site
Matsumoto, Nagano, 390-8621
Novartis Investigative Site
Sagamihara, Kanagawa, 252-0375
Hungary2 sites
Novartis Investigative Site
Balatonfüred, 8230
Novartis Investigative Site
Budapest, Pest County, 1134
India2 sites
Novartis Investigative Site
Belagavi, Karnataka, 590010
Novartis Investigative Site
Bikaner, Rajasthan, 334003
Portugal2 sites
Novartis Investigative Site
Lisbon, 1449-005
Novartis Investigative Site
Vila Nova de Gaia, 4434 502
About this study
Official title: A Multi-center, Randomized, Placebo- and Active-controlled, Parallel-group, 24-week Proof of Concept and Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Heart Failure
This was a multicenter, randomized, placebo- and active-controlled, parallel-group, 24-week trial to investigate the efficacy, safety, and tolerability of XXB750 in participants with HFrEF/HFmrEF.
Read the detailed description
Eligible participants were randomized to receive either subcutaneous (s.c.) XXB750 or placebo; or sacubitril/valsartan for 16 weeks, and then followed-up for 8 weeks.
The study planned to randomize adult participants with LVEF < 50% receiving ACEI/ARB/ARNI and guideline-recommended HF therapies for HFrEF or HFmrEF to three XXB750 target dose levels; a cohort of participants treated with ACEI/ARB before the study was randomized to be converted to open-label sacubitril/valsartan in place of their pre-study ACEI/ARB. A total of 720 participants were planned to be randomized in this study.
Due to safety concerns, in August 2024 the study was halted and dosing of all double-blind injectable medication of XXB750 and matching Placebo was suspended until further notice. All randomized participants actively involved in the study continued to attend study visits as per the study schedule and underwent all study procedures. This included safety, pharmacokinetic, antidrug antibody, and biomarker biological sample collections, physical examinations, and reporting of adverse events. As directed above, injectable study medication (i.e., XXB750 and its matching Placebo) was not administered. On 26-Sep-2024, Novartis made the decision to terminate the study due to safety findings and DMC recommendation.
Due to the early study termination, all participants who had been randomized to receive XXB750 or Placebo were followed up for 12 weeks after they received the last dose which is in accordance with the originally planned follow-up duration as per protocol. Participants who were randomized to the open-label treatment arm 5 and received sacubitril/valsartan as study medication were not further followed up after discontinuation of the open-label study medication. Sacubitril/valsartan is authorized in all participating countries and was, within this study, used as a comparator within the respective labels only. Hence, an additional follow-up for the safety of the participants was not performed; and the investigator could treat the participant with standard-of-care treatment (which includes sacubitril/valsartan) as per his/her clinical judgment.
To help guard the safety of study participants, randomization initially excluded the planned highest target dose of 240 mg XXB750 (i.e., arm 4). The study was terminated prematurely prior to the pre-planned early safety analysis due to an imbalance in worsening heart failure events among participants randomized to XXB750 60 mg and 120 mg. Thus, no participants were exposed to the planned highest target dose of 240 mg every 4 weeks.
- Conditions
- Heart Failure
- Being tested
- Placebo, XXB750 Low dose, XXB750 Medium Dose, XXB750 High Dose, Sacubitril/valsartan
- Keywords
- Heart failure, randomized, double-blind, dose finding, 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.
PlaceboBiological
S.C. Injection
XXB750 Low doseBiological
S.C. Injection
XXB750 Medium DoseBiological
S.C. Injection
XXB750 High DoseBiological
S.C. Injection
Sacubitril/valsartanDrug
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Placebo comparator | XXB750 Placebo Receives: Biological: Placebo |
| Arm 2 | Experimental | XXB750 60 mg Receives: Biological: XXB750 Low dose |
| Arm 3 | Experimental | XXB750 120 mg Receives: Biological: XXB750 Medium Dose |
| Arm 4 | Experimental | XXB750 240 mg Receives: Biological: XXB750 High Dose |
| Arm 5 | Active comparator | Sacubitril/valsartan, open label tablet, 97/103 mg bid (Sac/Val) Receives: Drug: Sacubitril/valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Ratio to Baseline in NT-proBNP at Week 16
Summary statistics for observed NT-proBNP values are reported: Geometric mean ratio to baseline at week 16 is calculated by the geometric mean of the ratio of the week 16 value to the baseline value. Baseline is defined as the value at randomization visit.
Measured: Baseline and week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2023
- Study start12 Dec 2023
- Primary completion1 Nov 2024
- Study completion1 Nov 2024
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 136 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
- NCT06142383
- Sponsor's protocol ID
- CXXB750A12201
- Other IDs
- 2023-504678-39-00, 2023
- Status last verified
- Jan 2026
- First submitted
- 16 Nov 2023
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Solomon SD, McMurray JJV, Felker GM, Januzzi JL, Lam CSP, Voors AA, Claggett B, Nuehrenberg TG, Rizkala AR, Koch C, Zhu W, Lefkowitz MP. The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial. Nat Med. 2026 May;32(5):1694-1700. doi: 10.1038/s41591-026-04313-w. Epub 2026 Mar 30.
PubMed 41912806
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Placebo- and Active-controlled, Parallel-group, 24-week Proof of Concept and Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT06142383
- Acronym / sponsor ID
- CXXB750A12201
- Conditions
- Heart Failure
- Keywords
- Heart failure, randomized, double-blind, dose finding, XXB750
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 136 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Dec 2023 (actual)
- Primary completion
- 1 Nov 2024 (actual)
- Study completion
- 1 Nov 2024 (actual)
- First posted
- 21 Nov 2023 (actual)
- Results
- Posted 24 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, randomized, placebo- and active-controlled, parallel-group, 24-week trial to investigate the efficacy, safety, and tolerability of XXB750 in participants with HFrEF/HFmrEF.
Detailed description
Eligible participants were randomized to receive either subcutaneous (s.c.) XXB750 or placebo; or sacubitril/valsartan for 16 weeks, and then followed-up for 8 weeks.
The study planned to randomize adult participants with LVEF < 50% receiving ACEI/ARB/ARNI and guideline-recommended HF therapies for HFrEF or HFmrEF to three XXB750 target dose levels; a cohort of participants treated with ACEI/ARB before the study was randomized to be converted to open-label sacubitril/valsartan in place of their pre-study ACEI/ARB. A total of 720 participants were planned to be randomized in this study.
Due to safety concerns, in August 2024 the study was halted and dosing of all double-blind injectable medication of XXB750 and matching Placebo was suspended until further notice. All randomized participants actively involved in the study continued to attend study visits as per the study schedule and underwent all study procedures. This included safety, pharmacokinetic, antidrug antibody, and biomarker biological sample collections, physical examinations, and reporting of adverse events. As directed above, injectable study medication (i.e., XXB750 and its matching Placebo) was not administered. On 26-Sep-2024, Novartis made the decision to terminate the study due to safety findings and DMC recommendation.
Due to the early study termination, all participants who had been randomized to receive XXB750 or Placebo were followed up for 12 weeks after they received the last dose which is in accordance with the originally planned follow-up duration as per protocol. Participants who were randomized to the open-label treatment arm 5 and received sacubitril/valsartan as study medication were not further followed up after discontinuation of the open-label study medication. Sacubitril/valsartan is authorized in all participating countries and was, within this study, used as a comparator within the respective labels only. Hence, an additional follow-up for the safety of the participants was not performed; and the investigator could treat the participant with standard-of-care treatment (which includes sacubitril/valsartan) as per his/her clinical judgment.
To help guard the safety of study participants, randomization initially excluded the planned highest target dose of 240 mg XXB750 (i.e., arm 4). The study was terminated prematurely prior to the pre-planned early safety analysis due to an imbalance in worsening heart failure events among participants randomized to XXB750 60 mg and 120 mg. Thus, no participants were exposed to the planned highest target dose of 240 mg every 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Placebo comparator | Biological: PlaceboXXB750 Placebo |
| Arm 2 | Experimental | Biological: XXB750 Low doseXXB750 60 mg |
| Arm 3 | Experimental | Biological: XXB750 Medium DoseXXB750 120 mg |
| Arm 4 | Experimental | Biological: XXB750 High DoseXXB750 240 mg |
| Arm 5 | Active comparator | Drug: Sacubitril/valsartanSacubitril/valsartan, open label tablet, 97/103 mg bid (Sac/Val) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Current symptom(s) of HF NYHA class II-III and LVEF < 50%
- Elevated NT-proBNP levels at screening.
- Receiving standard of care background HF therapy.
Key exclusion criteria (4 listed)
- Current acute decompensated HF or hospitalization for HF within 3 months prior to screening.
- Current symptomatic hypotension (for example dizziness/presyncope).
- K+ > 5.4 mmol/L at screening
- eGFR < 30 mL/min/1.73m2 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 |
|---|---|---|
| PlaceboS.C. Injection | Biological | Arm 1 |
| XXB750 Low doseS.C. Injection | Biological | Arm 2 |
| XXB750 Medium DoseS.C. Injection | Biological | Arm 3 |
| XXB750 High DoseS.C. Injection | Biological | Arm 4 |
| Sacubitril/valsartanTablet | Drug | Arm 5 |
Primary outcome
Geometric Mean Ratio to Baseline in NT-proBNP at Week 16
Time frame: Baseline and week 16
Summary statistics for observed NT-proBNP values are reported: Geometric mean ratio to baseline at week 16 is calculated by the geometric mean of the ratio of the week 16 value to the baseline value. Baseline is defined as the value at randomization visit.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41912806Solomon SD, McMurray JJV, Felker GM, Januzzi JL, Lam CSP, Voors AA, Claggett B, Nuehrenberg TG, Rizkala AR, Koch C, Zhu W, Lefkowitz MP. The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial. Nat Med. 2026 May;32(5):1694-1700. doi: 10.1038/s41591-026-04313-w. Epub 2026 Mar 30.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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
62 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing XXB750 Low dose, XXB750 Medium Dose and XXB750 High Dose in people with Heart Failure, run by Novartis Pharmaceuticals at 62 sites in 12 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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, Bulgaria, Spain, Germany, Italy and 7 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Geometric Mean Ratio to Baseline in NT-proBNP at Week 16 (time frame: Baseline and week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06142383, which also lists 1 linked publication.
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 27 Jan 2026.