A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BC 007 in Healthy Subjects
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      Berlin Cures develops BC 007 to treat patients suffering from diseases (chronic heart
      failure, pulmonary hypertension, chronic fatigue syndrome etc.) which are associated with
      functional autoantibodies (AAB) directed against G-protein coupled receptors (GPCR).

      The first part of the study (part A) is designed to evaluate the safety and tolerability of
      ascending doses of BC 007. The study part is blinded and placebo controlled in order to
      better discriminate possible safety signals. The assessment of safety and tolerability in an
      elderly cohort is a bridge to dosing elderly GPCR AAB positive subjects in part B. The
      subjects in part A are confirmed to be GPCR AAB negative.

      The objective of the second part of the study (part B) is to evaluate the efficacy of BC 007
      in neutralizing AAB against GPCR shortly after dosing compared to baseline and to find the
      optimal dose for the neutralization of the AAB in all individuals. This dose shall be taken
      to progress into a Phase II/III trial with beta1-adrenergic receptor-AAB positive patients
      suffering from chronic heart failure.
    

Detailed description: 
      Part A

      Primary objective is:

        -  To assess safety and tolerability of BC 007 after a single ascending intravenous (i.v.)
           bolus + infusion in healthy, young and elderly subjects.

      Secondary objectives are:

        -  To determine the pharmacokinetic plasma and urine profiles of BC 007 in healthy, young
           and elderly subjects.

      Part B

      Primary objective is:

        -  To assess the neutralizing potency of BC 007 against GPCR autoantibodies alpha -1
           adrenergic receptor, beta-1 adrenergic receptor, beta-2 adrenergic receptor or
           endothelin-A-receptor following ascending i.v. bolus + infusion.

      Secondary objectives are:

        -  To assess safety and tolerability of BC 007 after a single ascending i.v. bolus +
           infusion in GPCR AAB (α(1)-adrenergic receptor AAB, ß(1)-adrenergic receptor AAB,
           ß(2)-adrenergic receptor AAB or endothelin-A-receptor AAB) positive healthy elderly
           subjects.

        -  To determine the pharmacokinetic plasma and urine profiles of BC 007 in GPCR AAB
           (α(1)-adrenergic receptor AAB, ß(1)-adrenergic receptor AAB, ß(2)-adrenergic receptor
           AAB or endothelin-A-receptor AAB) positive healthy elderly subjects.

      Part C

      Primary Objective

        -  To assess the neutralizing potency of BC 007 against GPCR autoantibodies alpha-1
           adrenergic receptor (α(1)-AR AAB), beta-1 adrenergic receptor (ß(1)-AR AAB), beta-2
           adrenergic receptor (ß(2)-AR AAB) or endothelin-A-receptor (ETA AAB) following ascending
           i.v. bolus + infusion.

      Secondary Objectives

        -  To assess safety and tolerability of BC 007 after a single ascending i.v. bolus +
           infusion in GPCR AAB (α(1)-AR AAB, ß(1)-AR AAB, ß(2)-AR AAB or ETA AAB) positive healthy
           elderly subjects.

        -  To determine the pharmacokinetic plasma and urine profiles of BC 007 in GPCR AAB
           (α(1)-AR AAB, ß(1)-AR AAB, ß(2)-AR AAB or ETA AAB) positive healthy elderly subjects.

      Explorative Objective

        -  To investigate the pharmacokinetic plasma and urine profiles of BC 007 metabolites in
           GPCR AAB (α(1)-AR AAB, ß(1)-AR AAB, ß(2)-AR AAB or ETA AAB) positive healthy elderly
           subjects
    

Intervention name(s): BC 007; NaCl 0.9 %
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Autoantibodies; Heart Failure; Fatigue Syndrome, Chronic; Idiopathic Pulmonary Hypertension; Cardiomyopathies