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

NCT04192214 | Completed Phase 2

• 1 other identifier: SBC007C201
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cardiomyopathy, Dilated; Heart Failure; Autoantibodies

Outcome Measures

Primary Outcomes (1)

• Proportion of β1 AAb negative participants at month 12

  12 month

Secondary Outcomes (23)

• Persistence of response defined as the time from initial β1 AAb neutralisation to β1 AAb recurrence.

  12 month

• Response rate defined as the percentage of β1 AAb negative participants after a second treatment and persistence of response defined as the time from subsequent β1 AAb neutralisation to β1 AAb recurrence

  12 month

• Comparative conversion rate of β1 AAb from positive to negative status measured by a cardiomyocyte beat rate assay in untreated participants (control arm)

  12 month

• Number of Participants with abnormal laboratory values and/or adverse events that are related to treatment

  12 month

• Area under the plasma concentration time curve (AUC) from time zero to the last quantifiable concentration (AUC0-t) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

  6 hour post start of infusion

Other Outcomes (1)

• Echocardiographic parameter LVEF compared to untreated participants (control arm) from baseline to month 12

  12 month

Study Arms (2)

BC 007

ACTIVE COMPARATOR

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.

Drug: BC 007

Control

NO INTERVENTION

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.

Interventions

BC 007 DRUG

1350 mg of BC 007

BC 007

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Berlin Cures GmbH: lead

Study Sites (3)

Bežanijska Kosa Clinical and Hospital Centre

Belgrade, 11000, Serbia

Location

Institut za kardiovaskularne bolesti Dedinje

Belgrade, 11000, Serbia

Location

Zvezdara Clinical and Hospital Centre

Belgrade, 11000, Serbia

Location

Related Publications (3)

• Haberland A, Holtzhauer M, Schlichtiger A, Bartel S, Schimke I, Muller J, Dandel M, Luppa PB, Wallukat G. Aptamer BC 007 - A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors. Eur J Pharmacol. 2016 Oct 15;789:37-45. doi: 10.1016/j.ejphar.2016.06.061. Epub 2016 Jul 1.

  PMID: 27375076 BACKGROUND

• Wenzel K, Schulze-Rothe S, Haberland A, Muller J, Wallukat G, Davideit H. Performance and in-house validation of a bioassay for the determination of beta1-autoantibodies found in patients with cardiomyopathy. Heliyon. 2017 Jul 31;3(7):e00362. doi: 10.1016/j.heliyon.2017.e00362. eCollection 2017 Jul.

  PMID: 28795160 BACKGROUND

• Wallukat G, Muller J, Haberland A, Berg S, Schulz A, Freyse EJ, Vetter R, Salzsieder E, Kreutz R, Schimke I. Aptamer BC007 for neutralization of pathogenic autoantibodies directed against G-protein coupled receptors: A vision of future treatment of patients with cardiomyopathies and positivity for those autoantibodies. Atherosclerosis. 2016 Jan;244:44-7. doi: 10.1016/j.atherosclerosis.2015.11.001. Epub 2015 Nov 10.

  PMID: 26584137 BACKGROUND

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Johannes Müller, Dr.

  Berlin Cures GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 10, 2019
• Study Start: March 29, 2019
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3)