A Proof of Concept and Dose-finding Study of XXB750 in Patients With Heart Failure

January 7, 2026 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Blagoevgrad, Bulgaria, 270 0
        • Novartis Investigative Site
      • Gabrovo, Bulgaria, 5300
        • Novartis Investigative Site
      • Kyustendil, Bulgaria, 2500
        • Novartis Investigative Site
      • Pleven, Bulgaria, 5800
        • Novartis Investigative Site
      • Plovdiv, Bulgaria, 4002
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1233
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1510
        • Novartis Investigative Site
      • Varna, Bulgaria, 9010
        • Novartis Investigative Site
  • China
    • Shanxi
      • Xian, Shanxi, China, 710061
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13347
        • Novartis Investigative Site
      • Cologne, Germany, 51065
        • Novartis Investigative Site
      • Gladbeck, Germany, 45968
        • Novartis Investigative Site
      • Kiel, Germany, 24105
        • Novartis Investigative Site
      • Ludwigshafen, Germany, 67067
        • Novartis Investigative Site
      • Papenburg, Germany, 26871
        • Novartis Investigative Site
      • Schwäbisch Hall, Germany, 74523
        • Novartis Investigative Site
  • Hungary
      • Balatonfüred, Hungary, 8230
        • Novartis Investigative Site
    • Pest County
      • Budapest, Pest County, Hungary, 1134
        • Novartis Investigative Site
  • India
    • Karnataka
      • Belagavi, Karnataka, India, 590010
        • Novartis Investigative Site
    • Rajasthan
      • Bikaner, Rajasthan, India, 334003
        • Novartis Investigative Site
  • Italy
    • BS
      • Brescia, BS, Italy, 25123
        • Novartis Investigative Site
    • ME
      • Messina, ME, Italy, 98125
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italy, 20138
        • Novartis Investigative Site
    • PN
      • Pordenone, PN, Italy, 33170
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00168
        • Novartis Investigative Site
      • Roma, RM, Italy, 00133
        • Novartis Investigative Site
    • TS
      • Trieste, TS, Italy, 34149
        • Novartis Investigative Site
  • Japan
    • Gunma
      • Maebashi, Gunma, Japan, 371 8511
        • Novartis Investigative Site
    • Kanagawa
      • Kawasaki, Kanagawa, Japan, 216-8511
        • Novartis Investigative Site
      • Sagamihara, Kanagawa, Japan, 252-0375
        • Novartis Investigative Site
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Novartis Investigative Site
  • Portugal
      • Lisbon, Portugal, 1449-005
        • Novartis Investigative Site
      • Vila Nova de Gaia, Portugal, 4434 502
        • Novartis Investigative Site
  • Slovakia
    • Slovakia
      • Bardejov, Slovakia, Slovakia, 085 01
        • Novartis Investigative Site
      • Košice, Slovakia, Slovakia, 040 01
        • Novartis Investigative Site
      • Martin, Slovakia, Slovakia, 036 01
        • Novartis Investigative Site
      • Nitra, Slovakia, Slovakia, 949 11
        • Novartis Investigative Site
      • Prešov, Slovakia, Slovakia, 080 01
        • Novartis Investigative Site
      • Svidník, Slovakia, Slovakia, 089 01
        • Novartis Investigative Site
  • Spain
      • Las Palmas GC, Spain, 35010
        • Novartis Investigative Site
      • Madrid, Spain, 28041
        • Novartis Investigative Site
      • Málaga, Spain, 29010
        • Novartis Investigative Site
      • Valencia, Spain, 46026
        • Novartis Investigative Site
      • Valencia, Spain, 46010
        • Novartis Investigative Site
    • A Coruna
      • Santiago Compostela, A Coruna, Spain, 15706
        • Novartis Investigative Site
    • Andalusia
      • Huelva, Andalusia, Spain, 21005
        • Novartis Investigative Site
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Novartis Investigative Site
  • Taiwan
      • Taichung, Taiwan, 40447
        • Novartis Investigative Site
  • United States
    • Alabama
      • Dothan, Alabama, United States, 36305
        • SEC Clinical Research
      • Huntsville, Alabama, United States, 35801
        • Heart Center Research LLC
    • Florida
      • Inverness, Florida, United States, 34452
        • Nature Coast Clinical Research LLC
      • Miami Lakes, Florida, United States, 33014
        • Inpatient Research Clinical LLC
      • Wellington, Florida, United States, 33449
        • Cardiology Partners Clinical Research Institute
    • Georgia
      • Acworth, Georgia, United States, 30101
        • American Clinical Trials
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • The Research Group
    • Louisiana
      • Hammond, Louisiana, United States, 70403
        • Heart Clinic of Hammond
    • Maryland
      • Ft. Washington, Maryland, United States, 20744
        • Anderson Medical Research
    • Michigan
      • Troy, Michigan, United States, 48084
        • Revival Research Institute
    • Ohio
      • Canton, Ohio, United States, 44710
        • Aultman Hospital
      • Lima, Ohio, United States, 45801
        • Nexgen Research
    • Tennessee
      • Tullahoma, Tennessee, United States, 37388
        • Tennessee Center for Clinical Trials
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Dominion Medical Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Arm 1
XXB750 Placebo
Biological: Placebo
S.C. Injection
Experimental: Arm 2
XXB750 60 mg
Biological: XXB750 Low dose
S.C. Injection
Experimental: Arm 3
XXB750 120 mg
Biological: XXB750 Medium Dose
S.C. Injection
Experimental: Arm 4
XXB750 240 mg
Biological: XXB750 High Dose
S.C. Injection
Active Comparator: Arm 5
Sacubitril/valsartan, open label tablet, 97/103 mg bid (Sac/Val)
Drug: Sacubitril/valsartan
Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in log NT-proBNP from baseline to Week 16
Time Frame: Baseline to Week 16
To evaluate the efficacy of the highest and combined two highest XXB750 target dose levels compared to placebo and sacubitril/valsartan, respectively, in reducing NT-proBNP.
Baseline to Week 16

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline NT-proBNP Levels
Time Frame: Baseline
Baseline is defined as the NT-proBNP value at randomization visit.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2023

Primary Completion (Actual)

November 1, 2024

Study Completion (Actual)

November 1, 2024

Study Registration Dates

First Submitted

November 16, 2023

First Submitted That Met QC Criteria

November 16, 2023

First Posted (Actual)

November 21, 2023

Study Record Updates

Last Update Posted (Actual)

January 27, 2026

Last Update Submitted That Met QC Criteria

January 7, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CXXB750A12201
  • 2023-504678-39-00 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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