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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01798745
Recruitment Status : Withdrawn (study not required for development)
First Posted : February 26, 2013
Last Update Posted : April 9, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: JNJ-54452840 Other: Placebo Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Pharmacokinetic and Pharmacodynamic Two Part Cohort Study of JNJ-54452840 in Subjects With Reduced Systolic Function Heart Failure and Elevated Levels of Anti-Beta 1 Adrenergic Receptor Autoantibodies
Study Start Date : November 2014
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A: JNJ-54452840 20 mg
Each patient will receive 20 mg of JNJ-54452840 as a single dose.
 Drug: 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).
Experimental: Cohort A: JNJ-54452840 80 mg
Each patient will receive 80 mg of JNJ-54452840 as a single dose.
 Drug: 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).
Experimental: Cohort A: JNJ-54452840 160 mg
Each patient will receive 160 mg of JNJ-54452840 as a single dose.
 Drug: 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).
Placebo Comparator: Cohort A: Placebo
Each patient will receive matching placebo as a single dose.
 Other: 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).
Experimental: 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).
 Drug: 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).
Placebo Comparator: Cohort B: Placebo
Each patient will receive matching placebo as a single dose.
 Other: 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).
Experimental: 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).
 Drug: 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).
Placebo Comparator: Cohort C: Placebo
Each patient will receive matching placebo once daily for 3 days.
 Other: 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).
Experimental: 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).
 Drug: 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).
Placebo Comparator: Cohort D: Placebo
Each patient will receive matching placebo once daily for 5 days.
 Other: 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).
Experimental: 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).
 Drug: 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).
Placebo Comparator: Cohort E: Placebo
Each patient will receive matching placebo once weekly on Days 1, 8, 15, and 22.
 Other: 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).
Experimental: 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).
 Drug: 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).
Placebo Comparator: Cohort F: Placebo
Each patient will receive matching placebo once daily (for 3 or 5 days) or once weekly (up to Day 22).
 Other: 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).


Outcome Measures
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Primary Outcome Measures :
  1. Serum levels of anti-beta1-adrenergic receptor autoantibody bound JNJ-54452840 [ Time Frame: Up to Day 7 ]
    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).

  2. Serum levels of free JNJ-54452840 [ Time Frame: Up to Day 7 ]
    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).

  3. Serum levels of total JNJ-54452840 [ Time Frame: Up to Day 7 ]
    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).

  4. Serum levels of anti-beta1-adrenergic receptor autoantibodies [ Time Frame: Up to Day 85 ]
    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).

  5. Beta1-adrenergic receptor activation [ Time Frame: Up to Day 29 ]
    Beta1-adrenergic receptor activation will be used to determine the pharmacodynamics of JNJ-54452840 (ie, how the drug affects the body).


Secondary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Up to Day 85 ]
    Number of patients with adverse events will be used as a measure of safety and tolerability


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01798745


Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
More Information
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Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01798745    
Other Study ID Numbers: CR100985
54452840HFA2003 ( Other Identifier: Janssen Research & Development LLC )
2012-005302-22 ( EudraCT Number )
First Posted: February 26, 2013    Key Record Dates
Last Update Posted: April 9, 2014
Last Verified: April 2014
Keywords provided by Janssen Research & Development, LLC:
Heart failure
JNJ-54452840
Anti-beta-1 adrenergic receptor auto antibodies
Beta-1 adrenergic receptor
 Antibodies
Auto antibodies
Systolic function
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases