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

NCT ID: NCT06142383

Last Updated: 2025-12-24

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-12

Study Completion Date

2024-11-01

Brief Summary

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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

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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

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Heart Failure

Keywords

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Heart failure randomized double-blind dose finding XXB750

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Patients received either active XXB750 injection or a placebo injection that looks identical to the active injection. Sacubitril/valsartan was administered in an open-label fashion

Study Groups

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Arm 1

XXB750 Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

S.C. Injection

Arm 2

XXB750 60 mg

Group Type EXPERIMENTAL

XXB750 Low dose

Intervention Type BIOLOGICAL

S.C. Injection

Arm 3

XXB750 120 mg

Group Type EXPERIMENTAL

XXB750 Medium Dose

Intervention Type BIOLOGICAL

S.C. Injection

Arm 4

XXB750 240 mg

Group Type EXPERIMENTAL

XXB750 High Dose

Intervention Type BIOLOGICAL

S.C. Injection

Arm 5

Sacubitril/valsartan, open label tablet, 97/103 mg bid (Sac/Val)

Group Type ACTIVE_COMPARATOR

Sacubitril/valsartan

Intervention Type DRUG

Tablet

Interventions

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Placebo

S.C. Injection

Intervention Type BIOLOGICAL

XXB750 Low dose

S.C. Injection

Intervention Type BIOLOGICAL

XXB750 Medium Dose

S.C. Injection

Intervention Type BIOLOGICAL

XXB750 High Dose

S.C. Injection

Intervention Type BIOLOGICAL

Sacubitril/valsartan

Tablet

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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SEC Clinical Research

Dothan, Alabama, United States

Site Status

Heart Center Research Llc

Huntsville, Alabama, United States

Site Status

Nature Coast Clinical Research LLC

Inverness, Florida, United States

Site Status

Inpatient Research Clinical LLC

Miami Lakes, Florida, United States

Site Status

Cardiology Partners Clinical Research Institute

Wellington, Florida, United States

Site Status

American Clinical Trials

Acworth, Georgia, United States

Site Status

The Research Group

Lexington, Kentucky, United States

Site Status

Heart Clinic of Hammond

Hammond, Louisiana, United States

Site Status

Anderson Medical Research

Ft. Washington, Maryland, United States

Site Status

Revival Research Institute

Troy, Michigan, United States

Site Status

Aultman Hospital

Canton, Ohio, United States

Site Status

NexGen Research

Lima, Ohio, United States

Site Status

Tennessee Center For Clinical Trials

Tullahoma, Tennessee, United States

Site Status

Dominion Medical Associates

Richmond, Virginia, United States

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Novartis Investigative Site

Blagoevgrad, , Bulgaria

Site Status

Novartis Investigative Site

Gabrovo, , Bulgaria

Site Status

Novartis Investigative Site

Kyustendil, , Bulgaria

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Novartis Investigative Site

Pleven, , Bulgaria

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Novartis Investigative Site

Plovdiv, , Bulgaria

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Novartis Investigative Site

Sofia, , Bulgaria

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Novartis Investigative Site

Sofia, , Bulgaria

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Novartis Investigative Site

Varna, , Bulgaria

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Novartis Investigative Site

Xian, Shanxi, China

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Novartis Investigative Site

Berlin, , Germany

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Novartis Investigative Site

Cologne, , Germany

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Novartis Investigative Site

Gladbeck, , Germany

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Novartis Investigative Site

Kiel, , Germany

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Novartis Investigative Site

Ludwigshafen, , Germany

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Novartis Investigative Site

Papenburg, , Germany

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Novartis Investigative Site

Schwäbisch Hall, , Germany

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Novartis Investigative Site

Budapest, Pest County, Hungary

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Novartis Investigative Site

Balatonfüred, , Hungary

Site Status

Novartis Investigative Site

Belagavi, Karnataka, India

Site Status

Novartis Investigative Site

Bikaner, Rajasthan, India

Site Status

Novartis Investigative Site

Brescia, BS, Italy

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Novartis Investigative Site

Messina, ME, Italy

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Novartis Investigative Site

Milan, MI, Italy

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Novartis Investigative Site

Pordenone, PN, Italy

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Novartis Investigative Site

Roma, RM, Italy

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Novartis Investigative Site

Roma, RM, Italy

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Novartis Investigative Site

Trieste, TS, Italy

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Novartis Investigative Site

Maebashi, Gunma, Japan

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Novartis Investigative Site

Kawasaki, Kanagawa, Japan

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Novartis Investigative Site

Sagamihara, Kanagawa, Japan

Site Status

Novartis Investigative Site

Matsumoto, Nagano, Japan

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Novartis Investigative Site

Lisbon, , Portugal

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Novartis Investigative Site

Vila Nova de Gaia, , Portugal

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Novartis Investigative Site

Bardejov, Slovakia, Slovakia

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Novartis Investigative Site

Košice, Slovakia, Slovakia

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Novartis Investigative Site

Martin, Slovakia, Slovakia

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Novartis Investigative Site

Nitra, Slovakia, Slovakia

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Novartis Investigative Site

Prešov, Slovakia, Slovakia

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Novartis Investigative Site

Svidník, Slovakia, Slovakia

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Novartis Investigative Site

Santiago Compostela, A Coruna, Spain

Site Status

Novartis Investigative Site

Huelva, Andalusia, Spain

Site Status

Novartis Investigative Site

Majadahonda, Madrid, Spain

Site Status

Novartis Investigative Site

Las Palmas GC, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Málaga, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Taichung, , Taiwan

Site Status

Countries

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Czechia Denmark France Netherlands United Kingdom United States Bulgaria China Germany Hungary India Italy Japan Portugal Slovakia Spain Taiwan

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2023-504678-39-00

Identifier Type: OTHER

Identifier Source: secondary_id

CXXB750A12201

Identifier Type: -

Identifier Source: org_study_id