Phase 2
Completed N=194
A Dose Response Study of E6011 in Participants With Rheumatoid Arthritis Inadequately Responding to Methotrexate
Source: ClinicalTrials.gov NCT02960438 ↗Enrolled (actual)
194
Serious AEs
7.2%
Results posted
Jun 2021
Primary outcomePrimary: Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI) — 37.0; 39.3; 48.1; 46.3 percentage of participants — p=0.374
Summary
This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study in rheumatoid arthritis participants inadequately responding to methotrexate.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI) |
37.0; 39.3; 48.1; 46.3 | 0.374 |
| SECONDARY Treatment Phase: Percentage of Participants Who Achieved an ACR20 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI |
13.0; 14.3; 22.2; 20.4; 18.5; 28.6 | — |
| SECONDARY Treatment Phase: Percentage of Participants Who Achieved an ACR50 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI |
1.9; 0.0; 7.4; 7.4; 0.0; 3.6 | — |
| SECONDARY Treatment Phase: Percentage of Participants Who Achieved an ACR70 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI |
0.0; 0.0; 1.9; 0.0; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in Tender Joint Counts (TJC) at Each Visit Based on Last Observation Carried Forward (LOCF) |
13.7; 14.1; 16.3; 16.6; 13.6; 14.3 | — |
| SECONDARY Change From Baseline in Swollen Joint Counts (SJC) at Each Visit Based on LOCF |
12.7; 11.3; 12.4; 13.5; 12.7; 11.5 | — |
| SECONDARY Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF |
53.6; 47.9; 46.6; 52.9; 54.2; 46.6 | — |
| SECONDARY Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF |
53.1; 50.1; 49.0; 54.5; 53.4; 49.2 | — |
| SECONDARY Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF |
54.3; 53.1; 55.2; 54.2; 53.7; 52.0 | — |
| SECONDARY Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF |
0.77; 0.73; 0.75; 0.80; 0.75; 0.72 | — |
| SECONDARY Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF |
1.50; 1.44; 1.08; 1.24; 1.42; 1.41 | — |
| SECONDARY Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF |
41.6; 37.9; 40.8; 40.1; 39.6; 37.6 | — |
| SECONDARY Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF |
5.709; 5.687; 5.819; 5.984; 5.653; 5.674 | — |
| SECONDARY Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF |
5.039; 4.993; 5.079; 5.202; 4.997; 4.978 | — |
| SECONDARY Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF |
30.694; 30.546; 31.646; 34.413; 30.317; 30.604 | — |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF |
29.198; 29.104; 30.563; 33.169; 28.900; 29.196 | — |
| SECONDARY Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI |
3; 1; 2; 0; 3; 0 | — |
| SECONDARY Number of Participants With a EULAR Good or Moderate Response Using DAS28-CRP at Each Visit Based on NRI |
3; 1; 2; 0; 3; 1 | — |
| SECONDARY Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI |
1.9; 0.0; 0.0; 0.0; 2.1; 0.0 | — |
| SECONDARY Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI |
1.9; 0.0; 0.0; 0.0; 2.1; 0.0 | — |
| SECONDARY Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in Modified Total Sharp Score (mTSS) at Each Visit Based on Observed Cases (OC) |
27.20; 30.00; 37.55; 27.64; 17.08; 29.11 | — |
Eligibility Criteria
Inclusion Criteria
- Aged greater than or equal to (>=) 18 and less than ( =12 weeks before informed consent
- Received methotrexate (MTX) treatment at 6 to 16 milligram (mg)/week for >=12 weeks before screening and presented ≥6 tender joints (out of 68 joints) and >=6 swollen joints (out of 66 joints) in the Screening and Observation Phases
- Can continue stable dose regimen of MTX at 6 to 16 mg/week from 4 weeks before starting the study treatment until completion of the Extension Phase (or until study discontinuation)
- C-reactive protein (CRP) level >=0.6 mg/deciliter (dL) or erythrocyte sedimentation rate (ESR) >=28 millimeters per hour (mm/hr) in the Screening Phase
- Erosions at >=3 sites in radiographic image in the Screening Phase, or those with erosions at >=1 site and either positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody in the Screening Phase
- Weighs >=30 kilograms (kg) and ≤100 kg in the Screening Phase
- Has voluntarily consented, in writing, to participate in this study. If a participant is below the age of 20, also consented, in writing, by a legally acceptable representative.
- Has been thoroughly briefed on the conditions for participation in the study, is able to understand, and is willing and able to comply with all aspects of the protocol
Exclusion Criteria
- Any history or complication of inflammatory arthritic disorder other than RA or Sjogren's syndrome
- Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase
- Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment
- Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive
- Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, or renal disease) that could affect the participant's safety or interfere with the study assessments in the opinion of the investigator or subinvestigator
- Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage
- History of severe allergy (shock or anaphylactoid symptoms)
- History or current clinical condition of malignant tumor, lymphoma, leukemia, or lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal cell carcinoma) and cervix carcinoma which has completely excised and without metastasis or recurrence for more than 5 years before informed consent
- Immunodeficiency or history of human immunodeficiency virus (HIV) infection
- Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (example, herpes zoster) within 4 weeks before starting the study treatment
- History of tuberculosis or current complication of active tuberculosis
- History of clinically important vasculitis
- Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C virus antibody (HCV antibody), human T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis
- Positive in tuberculosis test (QuantiFERON®TB Gold Test or T-SPOT®.TB Test) in the Screening Phase
- Findings indicating a history of tuberculosis on chest x-ray in the Screening Phase
- Neurological findings such as paralysis, visual impairment, or language disorder in the Screening Phase
- Demonstrated prolonged QTcF interval (>450 milliseconds [ms]) in repeated electrocardiogram examinations
- Females of childbearing potential who have a positive pregnancy test in the Screening or Observation Phase or are breastfeeding
- Females of childbearing potential who:
- Had unprotected sexual intercourse within 30 days before study
Data sourced from ClinicalTrials.gov (NCT02960438). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.