A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BC 007 in Healthy Subjects

NCT02955420 | Completed Phase 1

• 2 other identifiers: SBC007C1012015-005236-18
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Autoantibodies; Heart Failure; Fatigue Syndrome, Chronic; Idiopathic Pulmonary Hypertension; Cardiomyopathies

Outcome Measures

Primary Outcomes (3)

• Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  24 hours post dose

• Part B: Conversion rate from positive GPCR AAB to negative immune status

  24 hours post dose

• Part C: Conversion rate from positive GPCR AAB to negative immune status

  24 hours and 8-12 days post dose

Secondary Outcomes (13)

• Part A, B and C: Area under the plasma concentration time curve (AUC) from time zero to the last quantifiable concentration (AUC0-t) derived from BC 007 plasma concentrations

  24 hours post dose

• Part A, B and C: Area under the plasma concentration time curve (AUC) from time zero extrapolated to infinity (AUC0-inf) derived from BC 007 plasma concentrations

  24 hours post dose

• Part A, B and C: AUC from time zero to 24 hour post-dose (AUC0-24) derived from BC 007 plasma concentrations

  24 hours post dose

• Part A, B and C: Maximum observed plasma concentration (Cmax) derived from BC 007 plasma concentrations

  24 hours post dose

• Part A, B and C: Apparent terminal half-life (t1/2) derived from BC 007 plasma concentrations

  24 hours post dose

Study Arms (1)

BC 007 (15, 50, 150, 300, 450, 750, 1350, 1200 mg)

EXPERIMENTAL

Part A: BC 007 at doses of 15, 50 and 150 mg or matching placebo administered as i.v. bolus + infusion of 20 min (Cohorts 1 to 4). The sentinel pair of each cohort will be dosed without bolus. NaCl 0.9% (matching placebo) administered as i.v. bolus + infusion of 20 min (Part A: Cohorts 1 to 4). Part B: BC 007 at doses of 50 and 150 mg administered (Cohort 1) or a single dose \< 50 mg or 150 mg (Cohort 2) as i.v. bolus + infusion of 20 min is administered to GPCR autoantibody positive subjects. The first subject in each dosing period of Cohort 1 will be dosed without bolus. Part C: BC007 administered at doses of 300 mg (Cohort 1), 450 mg (Cohort 2), 750 mg (Cohort 3), 1350 mg (Cohort 4) as i.v. bolus + infusion of 40 min to GPCR autoantibody positive subjects. The first three subjects in each dosing period of Cohort 1-4 will be dosed without bolus. In Cohort 5 BC007 dose of 1200 mg will be administered as a continuous infusion of 20 min.

Drug: BC 007; Drug: NaCl 0.9 %

Interventions

BC 007 DRUG

BC 007 (15, 50, 150, 300, 450, 750, 1350, 1200 mg)

NaCl 0.9 % DRUG

BC 007 (15, 50, 150, 300, 450, 750, 1350, 1200 mg)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject is a healthy, male, non-smoker or slight/occasional smoker (less than or equal to 10 cigarettes per day), 18 to 45 years of age (Cohorts 1 to 3, Part A).
• The subject is a healthy, male or female, non-smoker or slight/occasional smoker (less than or equal to10 cigarettes per day), 55 to 70 years of age (Cohort 4 \[only in Part A\] and Part B).
• Female subjects are postmenopausal (verified by an appropriate serum FSH level and amenorrhea for at least one year).
• The subject has a body mass index (BMI) range of 18.5 to 29.9 kg/m2 inclusive, (healthy young males as well as elderly subjects) and weighs at least 50 kg and \< 100 kg.
• The subject is positive for either one or the combination of GPCR α(1)- adrenergic receptor AAB, ß(1)-adrenergic receptor AAB, ß(2)-adrenergic receptor AAB and endothelin-A-receptor AAB (Part B only) at (pre-) screening prior to enrolment.
• The subject is negative for GPCR α(1)-adrenergic receptor AAB, ß(1)-adrenergic receptor AAB, ß(2)-adrenergic receptor AAB and endothelin-A-receptor AAB at (pre-)screening prior to enrolment (Part A only).
• Coagulation variables, uric acid, ALT, AST, alkaline phosphatase (ALP), GGT, bilirubin and creatinine must be within the normal laboratory reference ranges at screening.
• Thyroid-stimulating hormone (TSH) must be within the normal laboratory reference range at screening.

You may not qualify if:

• Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic (specifically gout), urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the Investigator.
• Any history or current intake of beta blockers.
• Any history of allergic reactions.

Sponsors & Collaborators

• Berlin Cures GmbH: lead

Study Sites (1)

PAREXEL International GmbH, Early Phase Clinical Unit Berlin

Berlin, 14050, Germany

Location

Related Publications (1)

• Becker NP, Haberland A, Wenzel K, Gottel P, Wallukat G, Davideit H, Schulze-Rothe S, Honicke AS, Schimke I, Bartel S, Grossmann M, Sinn A, Iavarone L, Boergermann JH, Prilliman K, Golor G, Muller J, Becker S. A Three-Part, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Mode of Action of BC 007, Neutraliser of Pathogenic Autoantibodies Against G-Protein Coupled Receptors in Healthy, Young and Elderly Subjects. Clin Drug Investig. 2020 May;40(5):433-447. doi: 10.1007/s40261-020-00903-9.

  PMID: 32222912 DERIVED

MeSH Terms

Conditions

Heart Failure; Fatigue Syndrome, Chronic; Familial Primary Pulmonary Hypertension; Cardiomyopathies

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Angela Sinn, Dr.

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 4, 2016
• Study Start: August 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: May 1, 2018
• Last Updated: July 18, 2018

Record last verified: 2018-07

Locations

DE (1)