A Phase 3 Study of Abatacept in Chinese Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

NCT02722694 | Unknown Phase 3

• 1 other identifier: SIM-126-III
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to demonstrate superior efficacy of abatacept 125mg administrated SC weekly comparing to placebo after 24 weeks treatment in Chinese subjects who have active rheumatoid arthritis, are receiving methotrexate and experiencing an inadequate response to methotrexate. This will be estimated by the proportion of subjects meeting the American College of Rheumatology (ACR) criteria for 20% improvement (ACR20).

Conditions

Rheumatoid Arthritis (RA)

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects meeting ACR 20 at 24 weeks (Day 169)

  The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein).

  Day 169

Secondary Outcomes (3)

• The proportion of subject meeting Health Assessment Questionnaire Disability Index (HAQ-DI) improvement at 24 weeks (Day 169)

  Day 169

• The proportion of subjects meeting ACR 50 at 24 weeks (Day 169)

  Day 169

• The proportion of subjects meeting ACR 70 at 24 weeks (Day 169)

  Day 169

Other Outcomes (7)

• The mean change of disease activity score from baseline by measuring DAS28-CRP at 24 weeks (Day 169)

  Day 169

• The mean change of HAQ-DI from baseline at 24 weeks (Day 169)

  Day 169

• Cmin of abatacept 125 mg administered SC weekly

  Day1 to Day196 in double-blind period

Study Arms (2)

Subcutaneous(SC) Abatacept

EXPERIMENTAL

Drug: Subcutaneous(SC) Abatacept; Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

Other: Placebo; Drug: Methotrexate

Interventions

Subcutaneous(SC) Abatacept DRUG

Subjects received 125mg weekly SC abatacept injections for 24 weeks. All subjects who complete 24 weeks double-blind treatment are eligible to enter open label period. During this period, subjects in placebo group will be switched to receive abatacept 125mg administered SC weekly till week 52. Subjects in abatacept group will continue to receive abatacept 125mg weekly.

Also known as: Orencia

Subcutaneous(SC) Abatacept

Placebo OTHER

Subjects received weekly SC placebo injections for 24 weeks

Placebo

Methotrexate DRUG

All Subjects received backup Methotrexate treatment.

Placebo; Subcutaneous(SC) Abatacept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are willing to participate in this study and sign informed consent;
• Subjects must meet the criteria of the America Rheumatism Association (1987) for the diagnosis of rheumatoid arthritis and ACR (1991) functional classes I, II or III;
• Subjects must have had Rheumatoid Arthritis for at least 6 months;
• Subjects who have inadequately response to MTX, must have been taking methotrexate for at least 3 months with minimal dose of 10 mg weekly, and at a stable dose for at least 28 days prior to randomization (Day 1). Methotrexate weekly dose as low as 7.5 mg is permitted for subjects who cannot tolerate higher dose, and the intolerance of higher dose than 7.5mg weekly should be well documented;
• Subjects must have the following disease activity at randomization:
• or more swollen joints(66 joint count);
• or more tender joints(68 joint count); and
• C reactive protein (hsCRP) \> 3 mg/L (based on the result of screening visit) or ESR ≥ 28mm/hr;
• All DMARDs (except methotrexate) should be discontinued for at least 28 days prior to study randomization (Day 1), Leflunomide must have been discontinued ≥8 weeks (the subject can be washed-out with cholestyramine according to label recommendations);
• Oral corticosteroid treatment must have been reduced to the prednisone ≤ 10 mg daily or equivalent for 28 days，and stabilized for at least 25 out of 28 days prior to randomization (Day 1). Corticosteroid administered by intra-articular (IA) or intramuscular (IM) will not be allowed 28 days prior to randomization (Day 1);
• Stable NSAIDs are permitted;
• Male and female subject ≥18 years old;
• Women of childbearing potential (WOCBP) must have a negative pregnancy test within 24 hours prior to the start of study medication;

You may not qualify if:

• WOCBP and male patients of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last dose of study medication;
• Women who are pregnant or breast-feeding;
• Women with a positive pregnancy test on enrollment or prior to study drug administration;
• Subjects meet diagnosis criteria of other rheumatoid disease (e.g., systemic lupus erythematosus);
• Subjects with active vasculitis of the major organ systems (except for subcutaneous rheumatoid nodules);
• Current symptoms of severe, progressive or uncontrolled diseases of renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral. Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study;
• Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. Subjects with carcinoma in situ, treated with definitive surgical intervention, are allowed;
• Subjects who have a history of drug or alcohol abuse;
• Subjects with any serious bacterial infection within the last 3 months (such as pneumonia or pyelonephritis, unless treated and resolved with antibiotics);
• Subjects with serious, chronic or recurrent bacterial infection (such as recurrent pneumonia and chronic bronchiectasis);
• Subjects at risk for tuberculosis (TB), Specially, :
• Having evidences of clinical, imaging or lab test of current active or latent pulmonary tuberculosis;
• Having active pulmonary tuberculosis during the past 3 years, even if had treated;
• Having history of active pulmonary tuberculosis more than 3 years ago, unless the appropriate duration and types of anti-tuberculosis drug is well documented;
• Subjects with herpes zoster that resolved less than 2 months before enrollment;

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Peking union medical college hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Xiaofeng Zeng

CONTACT

86-10-69158793; xiaofeng.zeng@cstar.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: March 30, 2016
• Study Start: August 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 13, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)