A Study to Assess the Pharmacokinetics and Pharmacodynamics of JNJ-54452840 in Participants With Heart Failure and Anti-beta1-adrenergic Receptor Autoantibodies

NCT01798745 | Withdrawn Phase 2 DMC

• 3 other identifiers: CR10098554452840HFA20032012-005302-22
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of JNJ-54452840 in participants with heart failure and anti-beta1-adrenergic receptor autoantibodies. The safety and tolerability of JNJ-54452840 will also be assessed.

Conditions

Heart Failure

Keywords

Heart failure; JNJ-54452840; Anti-beta-1 adrenergic receptor auto antibodies; Beta-1 adrenergic receptor; Antibodies; Auto antibodies; Systolic function

Outcome Measures

Primary Outcomes (5)

• Serum levels of anti-beta1-adrenergic receptor autoantibody bound JNJ-54452840

  Serum levels of bound JNJ-54452840 (ie, amount of drug that is attached to anti-beta1-adrenergic receptor autoantibodies) will be used to determine pharmacokinetic parameters for JNJ-54452840 (measurements describing how the body affects the drug).

  Up to Day 7

• Serum levels of free JNJ-54452840

  Serum levels of free JNJ-54452840 (ie, amount of drug that is not attached to anti-beta1-adrenergic receptor autoantibodies) will be used to determine pharmacokinetic parameters for JNJ-54452840 (measurements describing how the body affects the drug).

  Up to Day 7

• Serum levels of total JNJ-54452840

  Serum levels of total JNJ-54452840 (ie, bound drug plus free drug) will be used to determine pharmacokinetic parameters for JNJ-54452840 (measurements describing how the body affects the drug).

  Up to Day 7

• Serum levels of anti-beta1-adrenergic receptor autoantibodies

  Blood levels of anti-beta1-adrenergic receptor autoantibodies will be used to determine the pharmacodynamics of JNJ-54452840 (ie, how the drug affects the body).

  Up to Day 85

• Beta1-adrenergic receptor activation

  Beta1-adrenergic receptor activation will be used to determine the pharmacodynamics of JNJ-54452840 (ie, how the drug affects the body).

  Up to Day 29

Secondary Outcomes (1)

• Number of patients with adverse events

  Up to Day 85

Study Arms (14)

Cohort A: JNJ-54452840 20 mg

EXPERIMENTAL

Each patient will receive 20 mg of JNJ-54452840 as a single dose.

Drug: JNJ-54452840

Cohort A: JNJ-54452840 80 mg

EXPERIMENTAL

Each patient will receive 80 mg of JNJ-54452840 as a single dose.

Drug: JNJ-54452840

Cohort A: JNJ-54452840 160 mg

EXPERIMENTAL

Each patient will receive 160 mg of JNJ-54452840 as a single dose.

Drug: JNJ-54452840

Cohort A: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo as a single dose.

Other: Placebo

Cohort B: JNJ-54452840 <= 240 mg

EXPERIMENTAL

Each patient will receive JNJ-54452840 at a dose of less than or equal to 240 mg as a single dose (dose determined by the Data Monitoring Committee).

Drug: JNJ-54452840

Cohort B: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo as a single dose.

Other: Placebo

Cohort C: JNJ-54452840 for 3 days

EXPERIMENTAL

Each patient will receive JNJ-54452840 once daily for 3 days at a dose determined by the Data Monitoring Committee (daily dose not exceeding 240 mg).

Drug: JNJ-54452840

Cohort C: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo once daily for 3 days.

Other: Placebo

Cohort D: JNJ-54452840 for 5 days

EXPERIMENTAL

Each patient will receive JNJ-54452840 once daily for 5 days at a dose determined by the Data Monitoring Committee (daily dose not exceeding 240 mg).

Drug: JNJ-54452840

Cohort D: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo once daily for 5 days.

Other: Placebo

Cohort E: JNJ-54452840 weekly

EXPERIMENTAL

Each patient will receive JNJ-54452840 once weekly on Days 1, 8, 15, and 22 at a dose determined by the Data Monitoring Committee (daily dose not exceeding 240 mg).

Drug: JNJ-54452840

Cohort E: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo once weekly on Days 1, 8, 15, and 22.

Other: Placebo

Cohort F: JNJ-54452840 multiple dose

EXPERIMENTAL

Each patient will receive JNJ-54452840 once daily (for 3 or 5 days) or once weekly (up to Day 22) as determined by the Data Monitoring Committee and as explored in Cohorts C, D, and E (daily dose not exceeding 240 mg).

Drug: JNJ-54452840

Cohort F: Placebo

PLACEBO COMPARATOR

Each patient will receive matching placebo once daily (for 3 or 5 days) or once weekly (up to Day 22).

Other: Placebo

Interventions

JNJ-54452840 DRUG

Once daily intravenous injection(s) (medication is injected into a vein) at doses ranging from 20 mg to 240 mg, given as a single injection (Cohorts A and B); injections given once daily over 3 to 5 days (Cohorts C, D, and F); or injections given once weekly up to Day 22 (Cohorts E and F).

Cohort A: JNJ-54452840 160 mg; Cohort A: JNJ-54452840 20 mg; Cohort A: JNJ-54452840 80 mg; Cohort B: JNJ-54452840 <= 240 mg; Cohort C: JNJ-54452840 for 3 days; Cohort D: JNJ-54452840 for 5 days; Cohort E: JNJ-54452840 weekly; Cohort F: JNJ-54452840 multiple dose

Placebo OTHER

Once daily matching intravenous injection(s) (medication is injected into a vein) given as a single injection (Cohorts A and B); injections given once daily over 3 to 5 days (Cohorts C, D, and F); or injections given once weekly up to Day 22 (Cohorts E and F).

Cohort A: Placebo; Cohort B: Placebo; Cohort C: Placebo; Cohort D: Placebo; Cohort E: Placebo; Cohort F: Placebo

Eligibility Criteria

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

You may qualify if:

• Must have documented medical history of symptomatic (ie, showing symptoms) reduced ejection fraction (measurement of the percentage of blood leaving the heart each time it contracts) heart failure due to either ischemic etiology (decreased blood supply to heart) or non-ischemic dilated cardiomyopathy (heart is weakened and enlarged) for at least 4 months prior to the screening visit
• Must have heart failure classified by the New York Heart Association classification system as class I through IIIa
• Must have a left ventricular ejection fraction (measurement of the percentage of blood leaving the heart each time it contracts) of \< = 45%
• Must have blood levels of anti-beta1-adrenergic receptor autoantibodies (antibodies that are involved in developing heart failure) that are above the reference range
• Must have been receiving guideline-directed medical therapy for heart failure for at least 4 months prior to screening and, in addition, be receiving stable and individually optimized drug doses for at least 2 months prior to screening.

You may not qualify if:

• History of, or current active illness that, in the opinion of the investigator, would make participation not in the best interest (eg, compromise the well-being) of the patient or that could interfere with the study assessments
• Left ventricular end-diastolic diameter index (a measure of the heart's performance) of \<= 32 mm/m2
• N-terminal pro-brain natriuretic peptide level (a biologic molecule that has been shown to predict cardiac events) that is \<= 200 pg/mL in participants with normal sinus rhythm or \<= 800 pg/mL in participants with atrial fibrillation
• Chronic treatment with immunosuppressive drugs (except for \<= 5 mg/day prednisone-equivalent dose)
• Known allergies to peptides or proteins, such as albumin.

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

MeSH Terms

Conditions

Heart Failure

Interventions

JNJ-54452840

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2013
• First Posted: February 26, 2013
• Study Start: November 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 9, 2014

Record last verified: 2014-04