Arthritis, RheumatoidPhase 2NCT01469013
Oral Baricitinib (LY3009104)Treatment in Japanese Participants With Active Rheumatoid Arthritis on Background Methotrexate Therapy
A Phase 2 study testing Baricitinib and Methotrexate in people with Arthritis, Rheumatoid, run by Eli Lilly and Company at 14 sites in Japan.
Trial summary
This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of baricitinib (LY3009104) in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- Baricitinib and Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 145 participants
- Where
- 14 sitesJapan
- Study dates
- Nov 2011to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ambulatory males or females between the ages of 20 and 75 years, inclusive, at time of study entry
- Diagnosis of adult-onset RA (of at least 6 months duration but not longer than 15 years prior to screening) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Responder Index classification criteria for RA
- Have active RA defined as at least 6 swollen and at least 6 tender joints based on the 66/68 joint count
- Regular use of MTX for at least 12 weeks, and treatment at a stable dose of 6 to 16 mg/week (2 or 3 times a week) for at least 8 weeks prior to the treatment period. The dose of MTX should remain stable throughout the study, but may be adjusted for safety reasons.
- For participants receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to the treatment period
- Have C-Reactive Protein (CRP) measurement > 0.5 milligrams/deciliter (mg/dL) or Erythrocyte Sedimentation Rate (ESR) > 28 millimeters/hour (mm/hr). The CRP and ESR may be repeated once during the screening period at the discretion of the investigator, and the repeat results may be accepted for study eligibility purposes
Who cannot join
- Use of nonsteroidal anti-inflammatories (NSAIDs) for less than 4 weeks prior to the treatment period. If on NSAIDs, must be on a stable dose of the drug for at least 4 weeks prior to the treatment period and must remain on a stable dose throughout the study
- Received prior treatment with an oral Janus Kinase (JAK) inhibitor regardless of when they received it
- Have a diagnosis of Felty's syndrome
- Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
- Have hepatitis C virus (HCV; positive for anti-hepatitis C antibody with confirmed presence of HCV)
- Positive for hepatitis B surface antigen (HBsAg+), OR negative for hepatitis B surface antigen (HBsAg-), but positive for hepatitis B core antibody (HBcAb+) and/or positive for hepatitis B surface antibody (HBsAb+) with positive Hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) [≥2.1 Log copy/mL by Polymerase Chain Reaction (PCR) method] detected in the serum
- Have a positive result of the QuantiFERON®-tuberculosis (TB) Gold test (QFT-G) or a purified protein derivative (PPD) test
- Have estimated Glomerular Filtration Rate (GFR) from serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of <50 milliliter/minute (mL/min)
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Japan14 sites
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.
Chiba, 260-8712
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.
Fukuoka, 812-0025
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.
Hiroshima, 730-0017
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.
Hokkaido, 063-0811
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Hyōgo, 673-1462
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Ibaraki, 316-0035
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Kagoshima, 890-0067
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.
Kanagawa, 252-0392
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Nagasaki, 857-1165
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Ōita, 870-0823
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Okayama, 700-8607
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.
Osaka, 586-8521
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.
Tokyo, 130-0013
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.
Toyama, 933-0874
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2 Study of Baricitinib (LY3009104) in Japanese Patients With Active Rheumatoid Arthritis on Background Methotrexate Therapy
This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of baricitinib (LY3009104) in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. Baricitinib will be orally administered once a day with background methotrexate [6 to 16 milligrams (mg)/week] therapy for 12 weeks in the double-blind treatment period (1, 2, 4 or 8 mg/day, or placebo), and for 52 weeks in the single-blind extension period (4 or 8 mg/day).
- Conditions
- Arthritis, Rheumatoid
- Being tested
- Placebo, Baricitinib, Methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Sugar pill
BaricitinibDrug
Also called JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050
BaricitinibDrug
Also called JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050
BaricitinibDrug
Also called JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050
MethotrexateDrug
Administered orally as background therapy
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 2 placebo capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). Receives: Drug: Placebo; Drug: Methotrexate |
| 1-mg Baricitinib (LY3009104) | Experimental | 1 x 1-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). Receives: Drug: Placebo; Drug: Baricitinib; Drug: Methotrexate |
| 2-mg Baricitinib (LY3009104) | Experimental | 2 x 1-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). Receives: Drug: Baricitinib; Drug: Methotrexate |
| 4-mg Baricitinib (LY3009104) | Experimental | 1 x 4-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form. Receives: Drug: Placebo; Drug: Baricitinib; Drug: Methotrexate |
| 8-mg Baricitinib (LY3009104) | Experimental | 2 x 4-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form. Participants taking 8-mg baricitinib tablet form will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. Receives: Drug: Baricitinib; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 .
ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) , Patient's Global Assessment of Disease Activity-VAS (PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR20 response = (number of ACR20 responders) /(number of participants treated) * 100.
Measured: 12 weeks
Secondary outcomes (19)
Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks
ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI which measured participants perceived degree of difficulty performing daily activities, CRP and ESR, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) * 100.
Measured: Baseline up to 64 weeks
Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A)
ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR70 response=(number of ACR70 responders / number of participants treated) * 100.
Measured: Baseline up to 12 weeks
Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B)
ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR70 response=(number of ACR70 responders) / (number of participants treated) * 100.
Measured: Baseline up to 64 weeks
Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
DAS modified included the DAS28 that consisted of a composite score of the following variables: tender joint count out of 28 (TJC28), swollen joint count out of 28 (SJC28), CRP [milligrams per liter (mg/L)], and PtGADA on a 0 to 100 millimeter (mm) VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Measured: Baseline, 12 weeks
Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
DAS modified included the 28 diarthroidal joint count (DAS28) that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Measured: Baseline, 64 weeks
Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A)
EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP ≤3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: ≤3.2 and >1.2 improvement from baseline), moderate (absolute: >3.2 and ≤5.1 and >0.6 and ≤1.2 improvement from baseline), or no response (absolute: >5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) * 100.
Measured: Baseline up to 12 weeks
Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B)
EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP Responder Index defines a good (absolute: ≤3.2 and >1.2 improvement from baseline), moderate (absolute: >3.2 and ≤5.1 and >0.6 and ≤1.2 improvement from baseline), or no response (absolute: >5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) * 100.
Measured: Baseline up to 64 weeks
Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, patient and physician global assessment of disease activity and CRP. The equation used to calculate the SDAI:SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10, with lower values indicating fewer symptoms.
Measured: Baseline up to 12 weeks
Mean Change in SDAI Responses up to 64 Weeks (Part B)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI:
SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS/ 10, with lower values indicating fewer symptoms.
Measured: Baseline, 64 weeks
Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A)
HAQ-DI was a participant-reported questionnaire that consisted of 24 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 week using response categories: without any difficulty (0), with some difficulty (1), with much difficulty (2), and unable to do (3). 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 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Measured: Baseline, 12 weeks
Mean Change in HAQ-DI Responses up to 64 Weeks (Part B)
HAQ-DI was a participant-reported questionnaire that consisted of 24 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 week using response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). 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 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Measured: Baseline, 64 weeks
Mean Value of ACR-N Response (Part A)
The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of "X" has improvement of at least "X%" in tender and swollen joints and a median improvement of at least "X%" in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Measured: Baseline up to 12 weeks
Mean Value of ACR-N Response (Part B)
The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of "X" has improvement of at least "X%" in tender and swollen joints and a median improvement of at least "X%" in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Measured: Baseline up to 64 weeks
Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A)
DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. For remission, DAS28 is <2.6. Percentage of participants = (number of participants with DAS28 remission) / (number of participants treated) * 100.
Measured: Baseline up to 12 weeks
Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B)
DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA-VAS on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(sqrt of TJC28)+0.28(sqrt of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. For remission, DAS28 is <2.6. Percentage of participants = (number of participants with DAS 28 remission) / (number of participants treated) * 100.
Measured: Baseline up to 64 weeks
Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA and CRP. The equation used to calculate the SDAI:
SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) * 100
Measured: Baseline up to 12 weeks
Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI:
SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) * 100
Measured: Baseline up to 64 weeks
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
Steady state is achieved when the rate of drug input is equal to the rate of drug elimination. The AUC(tau,ss) at 1 dosing interval is the average concentration of the drug at steady state multiplied by the time of the dosing interval.
Measured: Weeks (Wks) 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Measured: Wks 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2012
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469013
- Sponsor's protocol ID
- 14116
- Other IDs
- I4V-JE-JADN
- Status last verified
- Sep 2019
- First submitted
- 8 Nov 2011
- Last updated
- 20 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Publications
Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.
PubMed 34706874Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019 Aug;78(8):1135-1138. doi: 10.1136/annrheumdis-2018-214261. Epub 2019 Mar 6. No abstract available.
PubMed 30842122Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.
PubMed 29463520Tanaka Y, Ishii T, Cai Z, Schlichting D, Rooney T, Macias W. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week, randomized, single-blind, extension study. Mod Rheumatol. 2018 Jan;28(1):20-29. doi: 10.1080/14397595.2017.1307899. Epub 2017 Apr 25.
PubMed 28440680Tanaka Y, Emoto K, Cai Z, Aoki T, Schlichting D, Rooney T, Macias W. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study. J Rheumatol. 2016 Mar;43(3):504-11. doi: 10.3899/jrheum.150613. Epub 2016 Feb 1.
PubMed 26834213
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2 Study of Baricitinib (LY3009104) in Japanese Patients With Active Rheumatoid Arthritis on Background Methotrexate Therapy
- ClinicalTrials.gov ID
- NCT01469013
- Acronym / sponsor ID
- 14116
- Conditions
- Arthritis, Rheumatoid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 10 Nov 2011 (estimated)
- Results
- Posted 1 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of baricitinib (LY3009104) in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. Baricitinib will be orally administered once a day with background methotrexate [6 to 16 milligrams (mg)/week] therapy for 12 weeks in the double-blind treatment period (1, 2, 4 or 8 mg/day, or placebo), and for 52 weeks in the single-blind extension period (4 or 8 mg/day).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: Methotrexate2 placebo capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). |
| 1-mg Baricitinib (LY3009104) | Experimental | Drug: Placebo, Drug: Baricitinib, Drug: Methotrexate1 x 1-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). |
| 2-mg Baricitinib (LY3009104) | Experimental | Drug: Baricitinib, Drug: Methotrexate2 x 1-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b). |
| 4-mg Baricitinib (LY3009104) | Experimental | Drug: Placebo, Drug: Baricitinib, Drug: Methotrexate1 x 4-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form. |
| 8-mg Baricitinib (LY3009104) | Experimental | Drug: Baricitinib, Drug: Methotrexate2 x 4-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form. Participants taking 8-mg baricitinib tablet form will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Ambulatory males or females between the ages of 20 and 75 years, inclusive, at time of study entry
- Diagnosis of adult-onset RA (of at least 6 months duration but not longer than 15 years prior to screening) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Responder Index classification criteria for RA
- Have active RA defined as at least 6 swollen and at least 6 tender joints based on the 66/68 joint count
- Regular use of MTX for at least 12 weeks, and treatment at a stable dose of 6 to 16 mg/week (2 or 3 times a week) for at least 8 weeks prior to the treatment period. The dose of MTX should remain stable throughout the study, but may be adjusted for safety reasons.
- For participants receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to the treatment period
Key exclusion criteria (8 listed)
- Use of nonsteroidal anti-inflammatories (NSAIDs) for less than 4 weeks prior to the treatment period. If on NSAIDs, must be on a stable dose of the drug for at least 4 weeks prior to the treatment period and must remain on a stable dose throughout the study
- Received prior treatment with an oral Janus Kinase (JAK) inhibitor regardless of when they received it
- Have a diagnosis of Felty's syndrome
- Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
- Have hepatitis C virus (HCV; positive for anti-hepatitis C antibody with confirmed presence of HCV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Sugar pill | Drug | 1-mg Baricitinib (LY3009104), 4-mg Baricitinib (LY3009104), Placebo |
| BaricitinibAlso: JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050 | Drug | 8-mg Baricitinib (LY3009104) |
| BaricitinibAlso: JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050 | Drug | 4-mg Baricitinib (LY3009104) |
| BaricitinibAlso: JAK1/JAK2 inhibitor, JAK1 inhibitor, JAK2 inhibitor, NCB028050 | Drug | 1-mg Baricitinib (LY3009104), 2-mg Baricitinib (LY3009104), 4-mg Baricitinib (LY3009104), 8-mg Baricitinib (LY3009104) |
| MethotrexateAdministered orally as background therapy | Drug | 1-mg Baricitinib (LY3009104), 2-mg Baricitinib (LY3009104), 4-mg Baricitinib (LY3009104), 8-mg Baricitinib (LY3009104), Placebo |
Primary outcome
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 .
Time frame: 12 weeks
ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) , Patient's Global Assessment of Disease Activity-VAS (PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR20 response = (number of ACR20 responders) /(number of participants treated) * 100.
19 secondary outcomes
Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks
Time frame: Baseline up to 64 weeks
Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A)
Time frame: Baseline up to 12 weeks
Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B)
Time frame: Baseline up to 64 weeks
Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
Time frame: Baseline, 12 weeks
Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
Time frame: Baseline, 64 weeks
Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A)
Time frame: Baseline up to 12 weeks
Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B)
Time frame: Baseline up to 64 weeks
Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A)
Time frame: Baseline up to 12 weeks
Mean Change in SDAI Responses up to 64 Weeks (Part B)
Time frame: Baseline, 64 weeks
Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A)
Time frame: Baseline, 12 weeks
Mean Change in HAQ-DI Responses up to 64 Weeks (Part B)
Time frame: Baseline, 64 weeks
Mean Value of ACR-N Response (Part A)
Time frame: Baseline up to 12 weeks
Mean Value of ACR-N Response (Part B)
Time frame: Baseline up to 64 weeks
Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A)
Time frame: Baseline up to 12 weeks
Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B)
Time frame: Baseline up to 64 weeks
Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A)
Time frame: Baseline up to 12 weeks
Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B)
Time frame: Baseline up to 64 weeks
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
Time frame: Weeks (Wks) 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Time frame: Wks 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34706874Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.
- Derived from this study: PubMed 30842122Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019 Aug;78(8):1135-1138. doi: 10.1136/annrheumdis-2018-214261. Epub 2019 Mar 6. No abstract available.
- Derived from this study: PubMed 29463520Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.
- Derived from this study: PubMed 28440680Tanaka Y, Ishii T, Cai Z, Schlichting D, Rooney T, Macias W. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week, randomized, single-blind, extension study. Mod Rheumatol. 2018 Jan;28(1):20-29. doi: 10.1080/14397595.2017.1307899. Epub 2017 Apr 25.
- Derived from this study: PubMed 26834213Tanaka Y, Emoto K, Cai Z, Aoki T, Schlichting D, Rooney T, Macias W. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study. J Rheumatol. 2016 Mar;43(3):504-11. doi: 10.3899/jrheum.150613. Epub 2016 Feb 1.
- Individual participant dataSharing planned: Yes. Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baricitinib and Methotrexate in people with Arthritis, Rheumatoid, run by Eli Lilly and Company at 14 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 . (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01469013, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2019.