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NCT Number: NCT04192214

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

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.

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Key information

Conditions

Cardiomyopathy, Dilated Autoantibodies Cardiomegaly Cardiomyopathies Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Heart Diseases Heart Failure Laminopathies

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Bežanijska Kosa Clinical and Hospital Centre, Belgrade, Serbia

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

BC 007

Drug

1350 mg of BC 007

Primary outcomes

  1. Proportion of β1 AAb negative participants at month 12

    Time frame: 12 month

Secondary outcomes

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

    Time frame: 12 month

  2. 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

    Time frame: 12 month

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

    Time frame: 12 month

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

    Time frame: 12 month

  5. 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

    Time frame: 6 hour post start of infusion

  6. Area under the plasma concentration time curve (AUC) from time zero extrapolated to infinity (AUC0-inf) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  7. Maximum observed plasma concentration (Cmax) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  8. Apparent terminal half-life (t1/2) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  9. Nominal time of Cmax (tmax) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  10. Plasma clearance (CL) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  11. Volume of distribution during terminal phase (Vz) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  12. Terminal elimination rate constant (λz) derived from BC 007 and BC 007 metabolite (N-1, N-2 and N-3) plasma concentrations

    Time frame: 6 hour post start of infusion

  13. Cumulative amount of unchanged drug excreted into urine (Ae)

    Time frame: 6 hour post start of infusion

  14. Fraction of intravenous administered drug that is excreted unchanged in urine (fe)

    Time frame: 6 hour post start of infusion

  15. Renal clearance (CLR) of BC 007

    Time frame: 6 hour post start of infusion

  16. Area under the plasma concentration time curve (AUC) from time zero to the last quantifiable concentration (AUC0-t) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 6 hour post start of infusion

  17. Area under the plasma concentration time curve (AUC) from time zero to the concentration after 4 hours (AUC0-4h) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 4 hour post start of infusion

  18. Area under the plasma concentration time curve (AUC) from time zero to the concentration after 6 hours (AUC0-6h) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 6 hour post start of infusion

  19. Area under the plasma concentration time curve (AUC) from time zero extrapolated to infinity (AUC0-inf) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 6 hour post start of infusion

  20. Maximum observed plasma concentration (Cmax) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 6 hour post start of infusion

  21. Nominal time of Cmax (tmax) derived from β-aminoisobutyric acid and uric acid plasma concentrations

    Time frame: 6 hour post start of infusion

  22. Cumulative amount of β-aminoisobutyric acid and uric acid excreted into urine (Ae)

    Time frame: 6 hour post start of infusion

  23. Renal clearance (CLR) of β-aminoisobutyric acid and uric acid

    Time frame: 6 hour post start of infusion

Other outcomes

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

    Time frame: 12 month

Sponsors and collaborators

Lead sponsor

Berlin Cures GmbH

Industry

Registry information

Official study title

A Two Arm Randomised, Open-label Study to Investigate the Persistence of Autoantibody Neutralisation, the Safety, and Pharmacokinetics of BC 007 in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) and Autoantibodies Directed Against the beta1 Adrenergic Receptor

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Dec 10, 2019
Registry last updated
Apr 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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