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

Lilly

Status and phase: Completed; Phase 2

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Methotrexate; Drug: Placebo; Drug: Baricitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01469013

I4V-JE-JADN (Other Identifier)

14116

Details and patient eligibility

About

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).

Enrollment: 145 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

145 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Methotrexate

Drug: Placebo

1-mg Baricitinib (LY3009104)

Experimental group

Description:

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).

Treatment:

Drug: Baricitinib

Drug: Methotrexate

Drug: Baricitinib

Drug: Placebo

Drug: Baricitinib

2-mg Baricitinib (LY3009104)

Experimental group

Description:

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).

Treatment:

Drug: Baricitinib

Drug: Methotrexate

Drug: Baricitinib

Drug: Baricitinib

4-mg Baricitinib (LY3009104)

Experimental group

Description:

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.

Treatment:

Drug: Baricitinib

Drug: Methotrexate

Drug: Baricitinib

Drug: Placebo

Drug: Baricitinib

8-mg Baricitinib (LY3009104)

Experimental group

Description:

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.

Treatment:

Drug: Baricitinib

Drug: Methotrexate

Drug: Baricitinib

Drug: Baricitinib