Oral Baricitinib (LY3009104)Treatment in Japanese Participants With Active Rheumatoid Arthritis on Background Methotrexate Therapy

NCT ID: NCT01469013

Last Updated: 2019-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-12-31

Brief 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. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Administered orally as background therapy

1-mg Baricitinib (LY3009104)

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).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Administered orally as background therapy

2-mg Baricitinib (LY3009104)

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).

Group Type: EXPERIMENTAL

Baricitinib

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Administered orally as background therapy

4-mg Baricitinib (LY3009104)

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Administered orally as background therapy

8-mg Baricitinib (LY3009104)

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.

Group Type: EXPERIMENTAL

Baricitinib

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Administered orally as background therapy

Interventions

Placebo

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Baricitinib

Intervention Type: DRUG

Methotrexate

Administered orally as background therapy

Intervention Type: DRUG

Other Intervention Names

Sugar pill; JAK1/JAK2 inhibitor; JAK1 inhibitor; JAK2 inhibitor; NCB028050; LY3009104; JAK1/JAK2 inhibitor; JAK1 inhibitor; JAK2 inhibitor; NCB028050; LY3009104; JAK1/JAK2 inhibitor; JAK1 inhibitor; JAK2 inhibitor; NCB028050; LY3009104

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal 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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

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.

Chiba, , Japan

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, , Japan

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, , Japan

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, , Japan

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.

Hyōgo, , Japan

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.

Ibaraki, , Japan

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.

Kagoshima, , Japan

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, , Japan

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.

Nagasaki, , Japan

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.

Okayama, , Japan

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, , Japan

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.

Ōita, , Japan

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, , Japan

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, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 34706874 (View on PubMed)

Combe 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.

Reference Type: DERIVED

PMID: 30842122 (View on PubMed)

Taylor 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.

Reference Type: DERIVED

PMID: 29463520 (View on PubMed)

Tanaka 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.

Reference Type: DERIVED

PMID: 28440680 (View on PubMed)

Tanaka 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.

Reference Type: DERIVED

PMID: 26834213 (View on PubMed)

Other Identifiers

I4V-JE-JADN

Identifier Type: OTHER

Identifier Source: secondary_id

14116

Identifier Type: -

Identifier Source: org_study_id