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

NCT ID: NCT01798745

Last Updated: 2014-04-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2015-12-31

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.

Detailed Description

This study will be randomized (the study treatment is assigned by chance), double-blind (neither investigator nor participant knows the treatment received), and placebo-controlled (one of the study treatments is inactive). This study will be conducted in participants with reduced systolic function heart failure (a reduced amount of blood is pumped around the body compared with a normal heart) and elevated levels of anti-beta1-adrenergic receptor autoantibodies (antibodies that may be involved in development, progression, or worsening of heart failure). The study will be conducted in 2 parts; participants will receive single doses of JNJ-54452840 in Part 1 and multiple doses in Part 2. Each part of the study will consist of 3 phases; a screening phase, a double-blind treatment phase, and a follow-up phase. There will be 2 cohorts (groups) of participants in Part 1 of the study. In Part 1 (Cohort A), participants will be randomly assigned to 1 of 4 treatment groups: a single intravenous (medication is injected into a vein) dose of 20 mg JNJ-54452840; a single intravenous dose of 80 mg JNJ-54452840; a single intravenous dose of 160 mg JNJ-54452840; or matching placebo (inactive medication). In Part 1 (Cohort B), participants will be randomly assigned to 1 of 2 treatment groups; a single intravenous dose of less than or equal to 240 mg JNJ-54452840 (as determined by the Data Review Committee after review of Cohort A data) or matching placebo. There will be 4 cohorts of participants in Part 2 of the study; the dose of JNJ-54452840 used in each cohort, initiation of each cohort, and the sequence will be decided by the Data Review Committee. In Part 2 (Cohort C), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once daily for 3 days. In Part 2 (Cohort D), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once daily for 5 days. In Part 2 (Cohort E), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once weekly on Days 1, 8, 15, and 22. In Part 2 (Cohort F), participants will be randomly assigned to 1 or more treatment groups involving regimen(s) as explored in Cohorts C, D, or E. Single doses of JNJ-54452840 will not be greater than 240 mg for any Cohort. The active to placebo randomization ratio for each cohort following Cohort A (ie, Cohorts B, C, D, E, and F) will be determined by the Data Review Committee. Participants will come to the study center each time they receive study medication and will remain at the center for at least two hours following each injection. Blood samples will be drawn at time points during the screening period and treatment period for participants in both Part 1 and Part 2 of the study. Participants will return to the study center after the double-blind treatment phase on Day 29 and then for follow-up visits on Days 57 and 85. Participants in Part 1 or Part 2 will be involved in the study for approximately 112 days. Participant safety will be monitored. The study drug, JNJ-54452480 is being investigated for the treatment of heart failure.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort A: JNJ-54452840 20 mg

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

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 80 mg

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

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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

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

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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: Placebo

Each patient will receive matching placebo as a single dose.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 B: JNJ-54452840 <= 240 mg

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).

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 B: Placebo

Each patient will receive matching placebo as a single dose.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 C: JNJ-54452840 for 3 days

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).

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 C: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 D: JNJ-54452840 for 5 days

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).

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 D: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 E: JNJ-54452840 weekly

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).

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 E: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 F: JNJ-54452840 multiple dose

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).

Group Type: EXPERIMENTAL

JNJ-54452840

Intervention Type: 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 F: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

JNJ-54452840

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).

Intervention Type: DRUG

Placebo

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).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

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

Other Identifiers

54452840HFA2003

Identifier Type: OTHER

Identifier Source: secondary_id

2012-005302-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100985

Identifier Type: -

Identifier Source: org_study_id