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

Healthy Volunteers Clinical Trial

Official title:

A Three-part, Randomized Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BC 007 in Healthy, Young Subjects and Elderly Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02955420
• Other study ID #: SBC007C101
• Secondary ID: 2015-005236-18
• Status: Completed
• Phase: Phase 1
• Start date: August 2016
• Est. completion date: May 2018

Study information

• Verified date: July 2018
• Source: Berlin Cures GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: May 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria (main):

1. 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).

2. 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).

3. Female subjects are postmenopausal (verified by an appropriate serum FSH level and amenorrhea for at least one year).

4. 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.

5. The subject is positive for either one or the combination of GPCR a(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.

6. The subject is negative for GPCR a(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).

7. Coagulation variables, uric acid, ALT, AST, alkaline phosphatase (ALP), GGT, bilirubin and creatinine must be within the normal laboratory reference ranges at screening.

8. Thyroid-stimulating hormone (TSH) must be within the normal laboratory reference range at screening.

Exclusion Criteria (main):

1. 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.

2. Any history or current intake of beta blockers.

3. Any history of allergic reactions.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• BC 007

• NaCl 0.9 %

Locations

Country	Name	City	State
Germany	PAREXEL International GmbH, Early Phase Clinical Unit Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Berlin Cures GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		24 hours post dose
Primary	Part B: Conversion rate from positive GPCR AAB to negative immune status		24 hours post dose
Primary	Part C: Conversion rate from positive GPCR AAB to negative immune status		24 hours and 8-12 days post dose
Secondary	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
Secondary	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
Secondary	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
Secondary	Part A, B and C: Maximum observed plasma concentration (Cmax) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	Part A, B and C: Apparent terminal half-life (t1/2) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	Part A, B and C: Nominal time of Cmax (tmax) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	Part A, B and C: Plasma clearance (CL) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	Part A, B and C: Volume of distribution during terminal phase (Vz) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	Part A, B and C: Terminal elimination rate constant (?z) derived from BC 007 plasma concentrations		24 hours post dose
Secondary	A, B and C: Cumulative amount of unchanged drug excreted into urine (Ae)		24 hours post dose
Secondary	A, B and C: Fraction of intravenous administered drug that is excreted unchanged in urine (fe)		24 hours post dose
Secondary	Part A, B and C: Renal clearance (CLR) of BC 007		24 hours post dose
Secondary	Part A, B and C: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		24 hours post dose