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A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

LY2189102

placebo

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

diagnosis of rheumatoid arthritis
regular use of methotrexate
active rheumatoid arthritis

Exclusion Criteria:

Juvenile Rheumatoid Arthritis
evidence of tuberculosis
women who are pregnant or become pregnant during study, or are breast-feeding

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.
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

Placebo Comparator

Arm Label

Part A LY2189102 0.1 mg/kg/wk

Part A LY2189102 0.3 mg/kg/wk

Part A LY2189102 1.0 mg/kg/wk

Part A LY2189102 2.5 mg/kg/wk

Placebo

Arm Description

Part A: 2 times (x) 0.1 milligrams/kilogram/week (mg/kg/wk) Loading dose, then 0.1 mg/kg/wk) X 4 weeks (wks), intravenous (IV) Part B: 2 x 0.02 mg/kg/wk Loading dose, then 0.02 mg/kg/wk X 4 wks, IV

Part A: 2 x 0.3 mg/kg/wk Loading dose, then 0.3 mg/kg/wk X 4 wks, IV Part B: 2 x 0.15 mg/kg/wk Loading dose, then 0.15 mg/kg/wk X 4 wks, IV

Part A: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV Part B: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV

Part A: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV Part B: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV

IV, once weekly x 4 wks

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs)

Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of s SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Secondary Outcome Measures

Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102

AUC0-168 hr,ss of individual participants was calculated by equation AUC=Dose/Clearance (CL), where the CL was estimated using a population PK model. Time frame for Part B: Day 1 predose, immediately after infusion (IAI), Day 14 and 28: predose and IAI, and Day 63 (Convenient time);

Change From Baseline in Simple Disease Activity Index Score (SDAI)

SDAI is calculated as the sum of 5 components: tender joint count (TJC) and swollen joint count (SJC), Patient Global Assessment (PtGA) of disease activity visual analog scale (VAS) and Physician's Global Assessment of Disease Activity (PGA) VAS, and C-reactive protein (CRP). Total Score scale range is 0 (remission) to 86 (high disease activity). A negative change from baseline indicated an improvement. Least Squares (LS) mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

Change From Baseline in Disease Activity Score 28-Joint Count (DAS28)

DAS28-4 (crp) is a modification of the original DAS based on TJC and SJC based on 28 joint counts, PGA VAS. DAS28-4 (crp) calculated as: 0.56*square root (sqrt) (TJC)+0.28*sqrt(SJC)+0.36*ln(CRP+1)+0.014*PGA+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

Change From Baseline in C-Reactive Protein (CRP)

CRP is a biomarker associated with inflammation and structural damage. A negative change from baseline indicates improvement. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

Change From Baseline in Health Assessment Questionnaire (HAQ) Score

HAQ was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ score. If the participant had scores for fewer than 6 categories, the HAQ score was considered missing. The HAQ score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement.

Full Information

NCT ID

NCT00380744

First Posted

September 22, 2006

Last Updated

August 29, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00380744

Brief Title

A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

Official Title

A Phase 1b/2 Multiple-Dose Safety Study and Pharmacokinetic/ Pharmacodynamic Study of LY2189102 in Patients With Rheumatoid Arthritis

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to examine the safety and efficacy of this antibody in participants with rheumatoid arthritis. Part A of the study is an initial dose escalation phase Part B of the study is a randomized allocation of the entire dosing group to parallel treatment assignments

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

121 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A LY2189102 0.1 mg/kg/wk

Arm Type

Experimental

Arm Description

Part A: 2 times (x) 0.1 milligrams/kilogram/week (mg/kg/wk) Loading dose, then 0.1 mg/kg/wk) X 4 weeks (wks), intravenous (IV) Part B: 2 x 0.02 mg/kg/wk Loading dose, then 0.02 mg/kg/wk X 4 wks, IV

Arm Title

Part A LY2189102 0.3 mg/kg/wk

Arm Type

Experimental

Arm Description

Part A: 2 x 0.3 mg/kg/wk Loading dose, then 0.3 mg/kg/wk X 4 wks, IV Part B: 2 x 0.15 mg/kg/wk Loading dose, then 0.15 mg/kg/wk X 4 wks, IV

Arm Title

Part A LY2189102 1.0 mg/kg/wk

Arm Type

Experimental

Arm Description

Part A: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV Part B: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV

Arm Title

Part A LY2189102 2.5 mg/kg/wk

Arm Type

Experimental

Arm Description

Part A: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV Part B: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

IV, once weekly x 4 wks

Intervention Type

Drug

Intervention Name(s)

LY2189102

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events (AEs)

Description

Time Frame

Baseline up to Day 98

Secondary Outcome Measure Information:

Title

Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102

Description

Time Frame

Part A: Day 1 predose and IAI, 2days post infusion, Day 14 and Day 28 predose and IAI, Day 35, 63 (convenient time)

Title

Change From Baseline in Simple Disease Activity Index Score (SDAI)

Description

Time Frame

Baseline, Days 7, 21, 35, 63, and 98

Title

Change From Baseline in Disease Activity Score 28-Joint Count (DAS28)

Description

Time Frame

Baseline, Days 7, 21, 35, 63, and 98

Title

Change From Baseline in C-Reactive Protein (CRP)

Description

Time Frame

Baseline, Days 7, 14, 21, 28, 35, 63, and 98

Title

Change From Baseline in Health Assessment Questionnaire (HAQ) Score

Description

Time Frame

Baseline, Days 35, 63, and 98

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: diagnosis of rheumatoid arthritis regular use of methotrexate active rheumatoid arthritis Exclusion Criteria: Juvenile Rheumatoid Arthritis evidence of tuberculosis women who are pregnant or become pregnant during study, or are breast-feeding

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 9AM - 5PM 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

Tucson

State/Province

Arizona

ZIP/Postal Code

85712

Country

United States

Facility Name

City

Upland

State/Province

California

ZIP/Postal Code

91786

Country

United States

Facility Name

City

Miami

State/Province

Florida

ZIP/Postal Code

33169

Country

United States

Facility Name

City

Port Orange

State/Province

Florida

ZIP/Postal Code

32127

Country

United States

Facility Name

City

Vero Beach

State/Province

Florida

ZIP/Postal Code

32962

Country

United States

Facility Name

City

Meridian

State/Province

Idaho

ZIP/Postal Code

83642

Country

United States

Facility Name

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87102

Country

United States

Facility Name

City

Mayfield

State/Province

Ohio

ZIP/Postal Code

44143

Country

United States

Facility Name

City

Bend

State/Province

Oregon

ZIP/Postal Code

97701

Country

United States

Facility Name

City

Orangeburg

State/Province

South Carolina

ZIP/Postal Code

29118

Country

United States

Facility Name

City

Bialystok

ZIP/Postal Code

15 297

Country

Poland

Facility Name

City

Szczecin

ZIP/Postal Code

71-252

Country

Poland

Facility Name

City

Warsaw

ZIP/Postal Code

02-637

Country

Poland

Facility Name

City

Wroclaw

ZIP/Postal Code

53-137

Country

Poland

12. IPD Sharing Statement

Citations:

PubMed Identifier

24912797

Citation

Bihorel S, Fiedler-Kelly J, Ludwig E, Sloan-Lancaster J, Raddad E. Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations. AAPS J. 2014 Sep;16(5):1009-17. doi: 10.1208/s12248-014-9623-6. Epub 2014 Jun 11.

Results Reference

derived

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A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

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