A Study in Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
LY2439821
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Ambulatory male or female patients between the ages of 20 and 75 years
- Male patients: Agree to use a reliable method of birth control during the study including barrier contraceptives or a monogamous relationship with a partner who is not child bearing. Female patients: Are women who test negative for pregnancy at the time of entry based on a pregnancy test and are not breast feeding. Women of child bearing potential must agree to use a reliable method of birth control during the study.
- Patients who are between the body weight of 40 and 105 kilogram (kg)
- Patients who have an established diagnosis of Rheumatoid Arthritis (RA)
- Patients who have C reactive protein (CRP) measurement greater than the upper limit of normal or erythrocyte sedimentation rate of at least 28 millimeters per hour (mm/hr)
- Patients who have been treated with regular use of Methotrexate (MTX) for at least 12 weeks, and stable treatment (at least 7.5 milligrams per week (mg/week)) for at least 8 weeks
- Patients who have given written informed consent approved by the Sponsor and the Institutional Review Board (IRB) governing the investigational site
- Patients who have reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria:
- Patients who use oral corticosteroids at average daily doses of >10 mg/day of prednisone or its equivalent or use of variable doses of oral corticosteroids within the last 4 weeks
- Patients who have had a live vaccination within the last 12 weeks, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within the last 12 weeks
- Patients who have a diagnosis of any systemic inflammatory condition other than RA
- Patients who have evidence of active vasculitis or uveitis
- Patients who have a diagnosis of Felty's syndrome
- Patients who have had surgical treatment of a joint within the last 8 weeks, or will require it during the study
- Patients who have had lymphoma, leukemia, or any malignancy within the last 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease
- Patients who have suffered a serious bacterial infection within the last 12 weeks, or a recent or ongoing infection
- Patients who have an evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or chest radiograph or documentation of TB by a positive purified protein derivative (PPD) test
- Patients who have uncontrolled arterial hypertension characterized by a systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg
- Patients who have an evidence of positive hepatitis B (HBV) surface antigen, positive hepatitis B surface antibody, positive hepatitis B core antibody, or hepatitis B DNA (HBV DNA); an evidence of human immunodeficiency virus (HIV), evidence of hepatitis B; or an evidence of hepatitis C
- Patients who have clinical laboratory test results at entry that are outside the normal reference range, or results with unacceptable deviations that are considered clinically significant by the investigator
- Patients who have a serum creatinine >2.0 milligrams per deciliter (mg/dL)
- Patients who have known hypogammaglobulinemia or a serum immunoglobulin (Ig) G (IgG), IgM, or IgA concentration less than the lower limit of normal
- Patients who have an abnormality in the 12 lead electrocardiogram (ECG).
- Patients who have donated of blood more than 200 mL within the past 30 days, or more than 400 milliliters (mL) within the past 90 days
- Patients who are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. For unapproved Disease-Modifying Anti-Rheumatic Drug (DMARDs), have received 30 days or 5 fold of the half life prior to inclusion whichever is longer
- Patients who previously completed or withdrawn from this study or any other study investigating LY2439821
- Patients who have been treated with any biologic DMARD currently or previously for 5 half lives
- Patients who have had serious reaction to other biologic Disease-Modifying Anti-Rheumatic Drug (DMARDs)
- Patients who have received non biologics DMARDs (other than MTX, sulfasalazine, bucillamine or hydroxychloroquine)
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
30 mg LY2439821
80 mg LY2439821
180 mg LY2439821
Placebo
120 mg LY2439821
Arm Description
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Placebo is administered subcutaneously in the same manner as active drug in each dose group
Administered subcutaneously at 240 mg as a single loading dose followed by 120 mg every week
Outcomes
Primary Outcome Measures
Number of Participants With Clinically Significant Effects
Clinically significant events were defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module.
Secondary Outcome Measures
Percentage Change From Baseline to 16 Week Endpoint in C-Reactive Protein
C-reactive protein (CRP) is a disease related biomarker and measured in milligrams per liter.
Percentage Change From Baseline to 16 Week Endpoint in Erythrocyte Sedimentation Rate (ESR)
Erythrocyte Sedimentation Rate (ESR) is a disease related biomarker and measured in millimeters per hour (mm/h).
Change From Baseline to 26 Week Endpoint in Neutrophil Counts
Change From Baseline to 26 Week Endpoint in Lymphocyte Counts
Pharmacokinetics - Area Under the Concentration-time Curve (AUC) at Steady State (ss)
AUCτ,ss= area under the concentration versus time curve (τ) at steady state (ss)
Pharmacokinetics - Maximum Plasma Drug Concentration (Cmax) at Steady State (ss)
Cmax,ss = maximum observed drug concentration (Cmax) at steady state (ss)
Pharmacokinetics - Time of Maximum Observed Drug Concentration (Tmax) at Steady State (ss)
tmax,ss = time of maximum observed drug concentration (tmax) at steady state (ss)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01253265
Brief Title
A Study in Rheumatoid Arthritis
Official Title
Multiple-Dose, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY2439821 in Japanese Patients With Rheumatoid Arthritis on Concomitant Methotrexate Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of multiple doses of LY2439821 in Japanese patients with rheumatoid arthritis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
30 mg LY2439821
Arm Type
Experimental
Arm Description
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Arm Title
80 mg LY2439821
Arm Type
Experimental
Arm Description
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Arm Title
180 mg LY2439821
Arm Type
Experimental
Arm Description
Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is administered subcutaneously in the same manner as active drug in each dose group
Arm Title
120 mg LY2439821
Arm Type
Experimental
Arm Description
Administered subcutaneously at 240 mg as a single loading dose followed by 120 mg every week
Intervention Type
Drug
Intervention Name(s)
LY2439821
Intervention Description
Administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered subcutaneously
Primary Outcome Measure Information:
Title
Number of Participants With Clinically Significant Effects
Description
Clinically significant events were defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module.
Time Frame
Baseline up to 26 weeks
Secondary Outcome Measure Information:
Title
Percentage Change From Baseline to 16 Week Endpoint in C-Reactive Protein
Description
C-reactive protein (CRP) is a disease related biomarker and measured in milligrams per liter.
Time Frame
Baseline, 16 weeks
Title
Percentage Change From Baseline to 16 Week Endpoint in Erythrocyte Sedimentation Rate (ESR)
Description
Erythrocyte Sedimentation Rate (ESR) is a disease related biomarker and measured in millimeters per hour (mm/h).
Time Frame
Baseline, 16 weeks
Title
Change From Baseline to 26 Week Endpoint in Neutrophil Counts
Time Frame
Baseline, 26 weeks
Title
Change From Baseline to 26 Week Endpoint in Lymphocyte Counts
Time Frame
Baseline, 26 weeks
Title
Pharmacokinetics - Area Under the Concentration-time Curve (AUC) at Steady State (ss)
Description
AUCτ,ss= area under the concentration versus time curve (τ) at steady state (ss)
Time Frame
Week 10 pre-dose up to 2 weeks post-dose (Week 12)
Title
Pharmacokinetics - Maximum Plasma Drug Concentration (Cmax) at Steady State (ss)
Description
Cmax,ss = maximum observed drug concentration (Cmax) at steady state (ss)
Time Frame
Week 10 pre-dose up to 2 weeks post-dose (Week 12)
Title
Pharmacokinetics - Time of Maximum Observed Drug Concentration (Tmax) at Steady State (ss)
Description
tmax,ss = time of maximum observed drug concentration (tmax) at steady state (ss)
Time Frame
Week 10 pre-dose up to 2 weeks post-dose (Week 12)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ambulatory male or female patients between the ages of 20 and 75 years
Male patients: Agree to use a reliable method of birth control during the study including barrier contraceptives or a monogamous relationship with a partner who is not child bearing. Female patients: Are women who test negative for pregnancy at the time of entry based on a pregnancy test and are not breast feeding. Women of child bearing potential must agree to use a reliable method of birth control during the study.
Patients who are between the body weight of 40 and 105 kilogram (kg)
Patients who have an established diagnosis of Rheumatoid Arthritis (RA)
Patients who have C reactive protein (CRP) measurement greater than the upper limit of normal or erythrocyte sedimentation rate of at least 28 millimeters per hour (mm/hr)
Patients who have been treated with regular use of Methotrexate (MTX) for at least 12 weeks, and stable treatment (at least 7.5 milligrams per week (mg/week)) for at least 8 weeks
Patients who have given written informed consent approved by the Sponsor and the Institutional Review Board (IRB) governing the investigational site
Patients who have reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria:
Patients who use oral corticosteroids at average daily doses of >10 mg/day of prednisone or its equivalent or use of variable doses of oral corticosteroids within the last 4 weeks
Patients who have had a live vaccination within the last 12 weeks, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within the last 12 weeks
Patients who have a diagnosis of any systemic inflammatory condition other than RA
Patients who have evidence of active vasculitis or uveitis
Patients who have a diagnosis of Felty's syndrome
Patients who have had surgical treatment of a joint within the last 8 weeks, or will require it during the study
Patients who have had lymphoma, leukemia, or any malignancy within the last 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease
Patients who have suffered a serious bacterial infection within the last 12 weeks, or a recent or ongoing infection
Patients who have an evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or chest radiograph or documentation of TB by a positive purified protein derivative (PPD) test
Patients who have uncontrolled arterial hypertension characterized by a systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg
Patients who have an evidence of positive hepatitis B (HBV) surface antigen, positive hepatitis B surface antibody, positive hepatitis B core antibody, or hepatitis B DNA (HBV DNA); an evidence of human immunodeficiency virus (HIV), evidence of hepatitis B; or an evidence of hepatitis C
Patients who have clinical laboratory test results at entry that are outside the normal reference range, or results with unacceptable deviations that are considered clinically significant by the investigator
Patients who have a serum creatinine >2.0 milligrams per deciliter (mg/dL)
Patients who have known hypogammaglobulinemia or a serum immunoglobulin (Ig) G (IgG), IgM, or IgA concentration less than the lower limit of normal
Patients who have an abnormality in the 12 lead electrocardiogram (ECG).
Patients who have donated of blood more than 200 mL within the past 30 days, or more than 400 milliliters (mL) within the past 90 days
Patients who are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. For unapproved Disease-Modifying Anti-Rheumatic Drug (DMARDs), have received 30 days or 5 fold of the half life prior to inclusion whichever is longer
Patients who previously completed or withdrawn from this study or any other study investigating LY2439821
Patients who have been treated with any biologic DMARD currently or previously for 5 half lives
Patients who have had serious reaction to other biologic Disease-Modifying Anti-Rheumatic Drug (DMARDs)
Patients who have received non biologics DMARDs (other than MTX, sulfasalazine, bucillamine or hydroxychloroquine)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Fukuoka
ZIP/Postal Code
820-8505
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Hyogo
ZIP/Postal Code
673-1462
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Ibaragi
ZIP/Postal Code
316-0035
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Nagasaki
ZIP/Postal Code
857-1165
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Niigata
ZIP/Postal Code
940-2085
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Okayama
ZIP/Postal Code
712-8044
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Shimane
ZIP/Postal Code
699-0293
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Tokyo
ZIP/Postal Code
164-8541
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
A Study in Rheumatoid Arthritis
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