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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00785928




Registration number
NCT00785928
Ethics application status
Date submitted
3/11/2008
Date registered
5/11/2008
Date last updated
10/07/2018

Titles & IDs
Public title
A Study for Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy
Scientific title
Phase 2, Dose-Ranging Study of Multiple Subcutaneous Doses of LY2127399 in Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy
Secondary ID [1] 0 0
H9B-MC-BCDH
Secondary ID [2] 0 0
12409
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - LY2127399
Treatment: Drugs - Placebo

Experimental: Placebo -

Experimental: 1 mg LY2127399 -

Experimental: 3 mg LY2127399 -

Experimental: 10 mg LY2127399 -

Experimental: 30 mg LY2127399 -

Experimental: 60 mg LY2127399 -

Experimental: 120 mg LY2127399 -


Treatment: Other: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).

Treatment: Drugs: Placebo
Administered subcutaneously (SC) every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response up to 24 Weeks
Assessment method [1] 0 0
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR50 Responder is defined as a participant with \>50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
Timepoint [1] 0 0
Up to week 24
Secondary outcome [1] 0 0
Percentage of Participants Achieving The American College of Rheumatology (ACR)20 Response up to 24 Weeks
Assessment method [1] 0 0
ACR20 Responder Index is composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
Timepoint [1] 0 0
Up to 24 weeks
Secondary outcome [2] 0 0
Change From Baseline in the Tender Joint Count up to 24 Weeks
Assessment method [2] 0 0
Number of tender and painful joints was determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. Participant was asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy.
Timepoint [2] 0 0
Baseline, up to 24 weeks
Secondary outcome [3] 0 0
Change From Baseline in Swollen Joint Count up to 24 Weeks
Assessment method [3] 0 0
The number of swollen joints was determined by examination of 28 joints which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
Timepoint [3] 0 0
Baseline, up to 24 weeks
Secondary outcome [4] 0 0
Change From Baseline in the Disease Activity Score (DAS) up to 24 Weeks
Assessment method [4] 0 0
DAS (modified to include the 28 joint count \[DAS28\]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of his or her disease activity (participant global visual analog scale \[pt global VAS\]). The DAS28 is calculated by using the following formula: DAS28-CRP = 0.56\*sqrt(28TJC) + 0.28\*sqrt(28SJC) + 0.36\*ln(CRP+1) + 0.014\*pt global VAS + 0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Timepoint [4] 0 0
Baseline, up to 24 weeks
Secondary outcome [5] 0 0
Percentage of Participants With A European League Against Rheumatism Responder Index Based on the 28 Joint Count (EULAR28) up to 24 Weeks
Assessment method [5] 0 0
The EULAR28 categorizes clinical response based upon improvement since baseline in the Disease Activity Score (DAS) modified to include the 28 joint count (DAS28) and post-baseline DAS28 level. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (participant global visual analog scale \[VAS\]). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units).
Timepoint [5] 0 0
Up to 24 weeks
Secondary outcome [6] 0 0
Change From Baseline in the Participant's Assessment of Joint Pain up to 24 Weeks
Assessment method [6] 0 0
Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Timepoint [6] 0 0
Baseline, up to 24 weeks
Secondary outcome [7] 0 0
Change From Baseline in the Participant's Assessment of Disease Activity up to 24 Weeks
Assessment method [7] 0 0
Participant's assessment of disease activity using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.
Timepoint [7] 0 0
Baseline, up to 24 weeks
Secondary outcome [8] 0 0
Change From Baseline in the Physician's Assessment of Disease Activity up to 24 Weeks
Assessment method [8] 0 0
Physician's assessment of disease activity using a visual analog scale (VAS) that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.
Timepoint [8] 0 0
Baseline, up to 24 weeks
Secondary outcome [9] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) up to 24 Weeks
Assessment method [9] 0 0
Participant's assessment of physical function. Disability section of questionnaire scores participant's self-perception on degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do) when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities. Scores for each of the functional areas were averaged to calculate the functional disability index. The HAQ-DI total score, which is the average of the nonmissing functional scores, ranges from 0 (no disability) to 3 (severe disability).
Timepoint [9] 0 0
Baseline, up to 24 weeks
Secondary outcome [10] 0 0
Percent Change From Baseline in C-Reactive Protein (CRP) up to 24 Weeks
Assessment method [10] 0 0
Percent change = \[(postbaseline CRP - baseline CRP)/baseline CRP\]\*100.
Timepoint [10] 0 0
Baseline, up to 24 weeks
Secondary outcome [11] 0 0
Change From Baseline in the Functional Assessment of Chronic Illness (FACIT) Fatigue Scale up to 24 Weeks
Assessment method [11] 0 0
The FACIT Fatigue Scale is a brief participant-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue.
Timepoint [11] 0 0
Baseline, up to 24 weeks
Secondary outcome [12] 0 0
Change From Baseline in the Short Form Health Survey (SF-36) up to 24 Weeks
Assessment method [12] 0 0
A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains. MCS and PCS scores = 0 to 100 (higher scores indicate better health status).
Timepoint [12] 0 0
Baseline, up to 24 weeks
Secondary outcome [13] 0 0
Pharmacokinetics of LY2127399: C-Trough Steady State Concentration at 24 Weeks
Assessment method [13] 0 0
C-trough is defined as the concentration of LY2127399 at the end of the dosing interval after the subcutaneous (sc) injection dosing once every 4 weeks. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.
Timepoint [13] 0 0
24 weeks
Secondary outcome [14] 0 0
Pharmacokinetics of LY2127399: T-Half Life (t1/2, Tau) at 24 Weeks
Assessment method [14] 0 0
T1/2,tau is defined as the apparent steady state elimination within the dosing interval. T1/2,tau was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.
Timepoint [14] 0 0
24 weeks
Secondary outcome [15] 0 0
Change From Baseline in the Absolute Total B Cell (CD20+CD3- Cells) Count up to 24 Weeks
Assessment method [15] 0 0
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. Total B cell counts (CD20+CD3-) are represented by the number of cells per microliter (cells/µL). The reference range is 43 - 602 cells/µL.
Timepoint [15] 0 0
Baseline, up to 24 weeks
Secondary outcome [16] 0 0
Change From Baseline in Serum Immunoglobulin up to 24 Weeks
Assessment method [16] 0 0
Serum immunoglobulin measured by Immunoglobulin G (IgG), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) levels.
Timepoint [16] 0 0
Baseline, up to 24 weeks
Secondary outcome [17] 0 0
Number of Participants Experiencing An Adverse Event
Assessment method [17] 0 0
Serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.
Timepoint [17] 0 0
Baseline up to 24 weeks

Eligibility
Key inclusion criteria
* Have given written informed consent
* Women must not be at risk to become pregnant during study participation
* Diagnosis of Rheumatoid Arthritis (RA)
* Current, regular use of Methotrexate, at a stable dose
* Other criteria to be reviewed by study doctor
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of excluded medications(reviewed by study doctor)
* Have not failed biologic tumor necrosis factor-alpha (TNF-a) inhibitor therapy
* Have had recent or ongoing infection which, in the opinion of the study doctor put patient at an unacceptable risk for participation in the study
* Evidence of tuberculosis
* Have systemic inflammatory condition other than RA, such as juvenile RA, Crohn's disease, ulcerative colitis, psoriatic arthritis or seronegative spondyloarthropathy
* Other criteria to be reviewed by study doctor

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2010
Sample size
Target
Accrual to date
Final
158
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
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. - Brisbane
Recruitment hospital [2] 0 0
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. - Maroochydore
Recruitment hospital [3] 0 0
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. - Elizabeth Vale
Recruitment postcode(s) [1] 0 0
4066 - Brisbane
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Quilmes
Country [8] 0 0
Chile
State/province [8] 0 0
Santiago
Country [9] 0 0
Chile
State/province [9] 0 0
Valdivia
Country [10] 0 0
Chile
State/province [10] 0 0
Vina Del Mar
Country [11] 0 0
Germany
State/province [11] 0 0
Leipzig
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Hungary
State/province [13] 0 0
Esztergom
Country [14] 0 0
Hungary
State/province [14] 0 0
Kistarcsa
Country [15] 0 0
Hungary
State/province [15] 0 0
Szolnok
Country [16] 0 0
India
State/province [16] 0 0
Hyderabaad
Country [17] 0 0
India
State/province [17] 0 0
Lucknow
Country [18] 0 0
India
State/province [18] 0 0
Pune
Country [19] 0 0
India
State/province [19] 0 0
Secunderabad
Country [20] 0 0
Mexico
State/province [20] 0 0
Chihuahua
Country [21] 0 0
Mexico
State/province [21] 0 0
Cuernavaca
Country [22] 0 0
Mexico
State/province [22] 0 0
Guadalajara
Country [23] 0 0
Mexico
State/province [23] 0 0
Mexico City
Country [24] 0 0
Mexico
State/province [24] 0 0
Monterrey
Country [25] 0 0
Mexico
State/province [25] 0 0
San Luis Potosi
Country [26] 0 0
Mexico
State/province [26] 0 0
Tampico
Country [27] 0 0
Poland
State/province [27] 0 0
Bialystok
Country [28] 0 0
Poland
State/province [28] 0 0
Chelm Slaski
Country [29] 0 0
Poland
State/province [29] 0 0
Elblag
Country [30] 0 0
Poland
State/province [30] 0 0
Krakow
Country [31] 0 0
Poland
State/province [31] 0 0
Lubin
Country [32] 0 0
Poland
State/province [32] 0 0
Lublin
Country [33] 0 0
Poland
State/province [33] 0 0
Poznan
Country [34] 0 0
Poland
State/province [34] 0 0
Torun
Country [35] 0 0
Poland
State/province [35] 0 0
Warsaw
Country [36] 0 0
Poland
State/province [36] 0 0
Wroclaw
Country [37] 0 0
Romania
State/province [37] 0 0
Brasov
Country [38] 0 0
Romania
State/province [38] 0 0
Targu-Mures
Country [39] 0 0
Slovakia
State/province [39] 0 0
Bratislava
Country [40] 0 0
Slovakia
State/province [40] 0 0
Rimavska
Country [41] 0 0
Ukraine
State/province [41] 0 0
Ivano-Frankivsk
Country [42] 0 0
Ukraine
State/province [42] 0 0
Kiev
Country [43] 0 0
Ukraine
State/province [43] 0 0
Odessa
Country [44] 0 0
Ukraine
State/province [44] 0 0
Simferopol

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLy (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00785928