The Persistence of Autoantibody Neutralisation by BC 007 in Patients With Chronic HFrEF and Autoantibodies Against the Beta1-Adrenergic Receptor

Berlin Cures

Status and phase: Completed; Phase 2

Conditions: Cardiomyopathy, Dilated; Autoantibodies; Heart Failure

Treatments: Drug: BC 007

Study type: Interventional

Funder types: Industry

Identifiers

NCT04192214

SBC007C201

Details and patient eligibility

About

Chronic heart failure (CHF) is one of the major causes of death in Western societies. Evidence has accumulated that functionally active autoantibodies directed against the beta1 adrenergic receptor (β1 AAb) are of pathophysiological relevance for the development and progression of cardiomyopathy and associated CHF. BC 007 is under development for targeted neutralisation of autoantibodies directed against G protein coupled receptors, including β1 AAb. This is an open label, three-centre, randomised phase 2a study in participants with chronic HFrEF. The study will evaluate whether BC 007 causes a persistent neutralisation of the β1 AAb demonstrated by a negative β1 AAb status up to 12 months. Participants will be randomised in a 2:1 ratio to the treatment arm (BC 007) or the control arm (untreated). Treatment is repeated once up to month 11 if the participant's β1 AAb were not neutralised after 1st dosing on day 1 or reoccur.

Full description

Primary objective is:

• To compare the efficacy of an intravenous (i.v.) infusion of BC 007 with an untreated control arm in removal of β1 AAb at month 12 in participants with chronic heart failure with reduced ejection fraction (HFrEF)

Secondary objectives are:

• To evaluate the time to recurrence of β1 AAb after a single i.v. infusion of BC 007
• To evaluate the response rate and time to recurrence of β1 AAb after a repeated single i.v. infusion of BC 007 after the first recurrence of β1 AAb
• To evaluate the safety and tolerability of BC 007 after a single and a repeated single i.v. infusion
• To determine the pharmacokinetic (PK) plasma and urine profiles of BC 007
• To investigate the PK plasma profiles of BC 007 metabolites
• To investigate the β aminoisobutyric acid (β-AIBA) plasma and urine, and uric acid serum and urine concentration as a marker for BC 007 degradation
• To investigate the spontaneous conversion of β1 AAb status from positive to negative in untreated participants (control arm)

Exploratory objective is:

• To evaluate the change of the left ventricular ejection fraction (LVEF) after a single and a repeated single i.v. infusion

Enrollment: 30 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participant ≥18 years of age, at the time of signing the informed consent.
• Participant has CHF class II III, according to the NYHA classification.
• Participant has a chronic HFrEF with a left ventricular ejection fraction (LVEF) ≤40 % during screening (as assessed by in-hospital echocardiography).
• Participant screened positive for β1 AAb by a validated functional assay.

Exclusion criteria

• Participant has a sustained systolic blood pressure ≥160 mmHg prior to randomisation.
• Participant has a sustained bradycardia with resting heart rate <45 beats per minute (bpm) or tachycardia with resting heart rate >100 bpm prior to randomisation.
• Participant has an untreated primary valvular disease, considered clinically significant by the Investigator.
• Participant has any condition or therapy, which would make the participant unsuitable for the study, or life expectancy less than 12 months (e.g., active malignancy).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

BC 007

Active Comparator group

Description:

The treatment arm will comprise 20 randomly allocated β1-AAb positive dilative cardiomyopathy (DCM) patients. Participants will receive a continuous 75 minute infusion of 1350 mg BC 007 at day 1. The β1-AAb status will be monitored 10 days after treatment and every month. Treatment is repeated once up to month 11 if the participant's β1-AAbs were not neutralized after 1st dosing on day 1 or reoccur.

Treatment:

Drug: BC 007

Control

No Intervention group

Description:

The control arm will comprise 10 randomly allocated β1-AAb positive DCM patients. Participants will receive standard therapy but no intervention. The β1- AAb status will be monitored every month.