Oral JAK1/JAK2 Selective Inhibitor Treatment in Japanese Participants With Active Rheumatoid Arthritis on Background Methotrexate Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01469013
First received: November 8, 2011
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of LY3009104 in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. LY3009104 will be orally administered once a day with background methotrexate (6 to 16 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).


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: LY3009104
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2 Study of LY3009104 in Japanese Patients With Active Rheumatoid Arthritis on Background Methotrexate Therapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of participants who achieve an American College of Rheumatology (ACR) 20 response at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of participants who achieve an ACR20 response from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve an ACR70 response from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Change in Disease Activity Score 28 Diarthroidal Joint Count (DAS28) response from baseline up to 64 weeks [ Time Frame: Baseline, up to 64 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) response from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Change in Simplified Disease Activity Index (SDAI) responses from baseline up to 64 weeks [ Time Frame: Baseline, up to 64 weeks ] [ Designated as safety issue: No ]
  • Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) responses from baseline up to 64 weeks [ Time Frame: Baseline, up to 64 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve an ACR-N response from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve a DAS28 remission from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who achieve an SDAI remission from baseline up to 64 weeks [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics: predicted concentration maximum (Cmax) of LY3009104 [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics: predicted area under the curve (AUC) of LY3009104 [ Time Frame: Baseline up to 64 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: November 2011
Study Completion Date: December 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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 LY3009104 or 8-mg LY3009104 arms. Participants rerandomized to 8-mg LY3009104 arm at Week12 will switch to 4-mg LY3009104 once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
Drug: Placebo
Capsules administered orally
Other Name: Sugar pill
Experimental: 1-mg LY3009104
1 x 1-mg LY3009104 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 LY3009104 or 8-mg LY3009104 arms. Participants rerandomized to 8-mg LY3009104 arm at Week 12 will switch to 4-mg LY3009104 once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
Drug: LY3009104
Capsules administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor
Drug: Placebo
Capsules administered orally
Other Name: Sugar pill
Experimental: 2-mg LY3009104
2 x 1-mg LY3001904 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 LY3009104 or 8-mg LY3009104 arms. Participants rerandomized to 8-mg LY3009104 arm at Week 12 will switch to 4-mg LY3009104 once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
Drug: LY3009104
Capsules administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor
Experimental: 4-mg LY3009104
1 x 4-mg LY3009104 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.
Drug: LY3009104
Capsules administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor
Drug: Placebo
Capsules administered orally
Other Name: Sugar pill
Drug: LY3009104
Tablets administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor
Drug: Placebo
Tablets administered orally
Other Name: Sugar pill
Experimental: 8-mg LY3009104
2 x 4-mg LY3009104 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 LY3009104 tablet form will switch to 4-mg LY3009104 once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.
Drug: LY3009104
Capsules administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor
Drug: LY3009104
Tablets administered orally
Other Names:
  • JAK1/JAK2 inhibitor
  • JAK1 inhibitor
  • JAK2 inhibitor

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ACR/EULAR 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 mg/dL or Erythrocyte Sedimentation Rate (ESR) > 28 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 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)-DNA (≥2.1 Log copy/mL by Polymerase Chain Reaction [PCR] method) detected in the serum
  • Have a positive result of the QuantiFERON®-TB Gold test 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 mL/min
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469013

Locations
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.
Chiba, Japan, 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, Japan, 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, Japan, 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, Japan, 063-0811
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.
Hyogo, Japan, 673-1462
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.
Ibaragi, Japan, 316-0035
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, 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, Japan, 252-0392
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, 857
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.
Oita, Japan, 870-0823
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, 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, Japan, 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, Japan, 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, Japan, 933-0874
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01469013     History of Changes
Other Study ID Numbers: 14116, I4V-JE-JADN
Study First Received: November 8, 2011
Last Updated: January 24, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014