Open-label Study to Assess the Safety and Efficacy of CDP6038 (Olokizumab) in Patients Who Completed RA0056

A Phase 2, Multicenter, Open-Label, Follow-up Study to Assess the Long-Term Safety and Efficacy of CDP6038 (Olokizumab) Administered Subcutaneously to Subjects With Active Rheumatoid Arthritis Who Completed Study RA0056

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01296711

Enrollment

190

Registered

2011-02-15

Start date

2011-03-07

Completion date

2013-08-05

Last updated

2022-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis, CDP6038, Interleukin-6

Brief summary

The purpose of this study is to evaluate the long term safety and tolerability of CDP6038 (olokizumab) treatment in adult subjects with active rheumatoid arthritis who completed study RA0056 (NCT01242488).

Detailed description

Male and female subjects were randomized in a multi-center, open-label, follow-up study to assess the long-term safety and efficacy of a subcutaneous dose of 120 mg CDP6038 (olokizumab), every two weeks, for the treatment of active rheumatoid arthritis.

Interventions

BIOLOGICALCDP6038 (olokizumab)

100mg/ml solution for injection 120 mg subcutaneously (sc) every 2 weeks

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

RA0057 is a single arm study, however, analyses will also be performed according to the original treatment arms of the parent study RA0056 (NCT01242488).

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subject completed the RA0056 study (Week 12 Visit) * Subject must have maintained their stable dose (and route) of methotrexate (MTX) between 12.5 to 25mg/week in RA0056, and plan to maintain this same dose and route of administration for at least 12 weeks * Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence is not considered an acceptable method of contraception for this study * Female subjects of childbearing potential must agree to use 2 methods of adequate contraception during the study and for 6 months (24 weeks) after their last CDP6038 (olokizumab) dose * Male subjects must agree to ensure that they or their female partner(s) use adequate contraception during the study and for 12 weeks after the subject receives their last dose of CDP6038 (olokizumab)

Exclusion criteria

* Subject has an ongoing serious adverse event from the RA0056 study * Female subject of childbearing potential has a positive pregnancy test at Week 12 in Study RA0056 or plans to become pregnant during the study or within 6 months (24 weeks) following their last dose of study medication * Subject has evidence of active or latent tuberculosis * Subject is receiving any biologic response modifier or synthetic disease-modifying antirheumatic drug other than MTX * Subject has an alcohol consumption of more than 1 unit per weekday. One unit equals 1 glass of beer or lager (\ 330mL), a glass of wine (125mL), or a measure of spirits/hard liquor (25mL) * Subject with any other condition in RA0056 (eg, clinically significant laboratory values, frequent adverse events) which in the Investigator's or Sponsor's judgment would make the subject unsuitable for inclusion in the study

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	From Baseline (Week 0 of Study RA0057) until 30 days after the last dose (maximum up to 780 days)	Reported TEAEs included adverse events that started or worsened after the first dose of CDP6038 (olokizumab) in Study RA0057 and within 30 days after the last dose.

Secondary

Measure	Time frame	Description
Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 24 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.
Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.
Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.
The American College of Rheumatology (ACR) 20% (ACR20) Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)	ACR20 represents at least 20% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, Physician's Global Assessment of Disease Activity (PhGADA)-VAS, Patient's Assessment of Arthritis Pain (PAAP)-VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR20 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)	ACR20 represents at least 20% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR20 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)	ACR20 represents at least 20% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR20 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)	ACR20 represents at least 20% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR 50% (ACR50) Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)	ACR50 represents at least 50% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR50 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)	ACR50 represents at least 50% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR50 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)	ACR50 represents at least 50% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores meaning less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR50 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)	ACR50 represents at least 50% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR 70% (ACR70) Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)	ACR70 represents at least 70% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
The ACR70 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)	ACR70 represents at least 70% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 12 (Study RA0057)	DAS28(CRP) was calculated using the tender/painful joint count (TJC) and swollen joint count (SJC) from 28 joints, the Patient's Global Assessment of Disease Activity (PtGADA)-Visual Analog Scale (VAS), andCRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.
The ACR70 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)	ACR70 represents at least 70% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.
Percentage of Subjects With DAS28(CRP) <2.6 at Week 12 of Study RA0057	Week 12 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than 2.6 implies remission.
Percentage of Subjects With DAS28(CRP) <2.6 at Week 24 of Study RA0057	Week 24 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than 2.6 implies remission.
Percentage of Subjects With DAS28(CRP) <2.6 at Week 48 of Study RA0057	Week 48 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than 2.6 implies remission.
Percentage of Subjects With DAS28(CRP) <2.6 at Week 96 of Study RA0057	Week 96 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than 2.6 implies remission.
Percentage of Subjects With DAS28(CRP) ≤3.2 at Week 12 of Study RA0057	Week 12 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than or equal to (\<=) 3.2 implies low disease activity.
Percentage of Subjects With DAS28(CRP) ≤3.2 at Week 24 of Study RA0057	Week 24 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score \<=3.2 implies low disease activity.
Percentage of Subjects With DAS28(CRP) ≤3.2 at Week 48 of Study RA0057	Week 48 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score \<=3.2 implies low disease activity.
Percentage of Subjects With DAS28(CRP) ≤3.2 at Week 96 of Study RA0057	Week 96 (Study RA0057)	DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score \<=3.2 implies low disease activity.
Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)	CDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS and PhGADA-VAS, according to the following formula: SJC + TJC + PtGADA + PhGADA Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Total score range is from 0-100, with the high scores representing high disease activity. A negative change in CDAI score indicates an improvement in disease activity.
Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)	CDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS and PhGADA-VAS, according to the following formula: SJC + TJC + PtGADA + PhGADA Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Total score range is from 0-100, with the high scores representing high disease activity. A negative change in CDAI score indicates an improvement in disease activity.
Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)	SDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS, PhGADA-VAS and CRP (in milligrams per decilitre \[mg/dL\]), according to the following formula: SJC + TJC + PtGADA + PhGADA + CRP (mg/dL) Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). • CRP range was from 0 to 10 mg/dL. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. A negative change in SDAI score indicates an improvement in disease activity.
Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)	SDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS, PhGADA-VAS and CRP (in milligrams per decilitre \[mg/dL\]), according to the following formula: SJC + TJC + PtGADA + PhGADA + CRP (mg/dL) Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). • CRP range was from 0 to 10 mg/dL. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. A negative change in SDAI score indicates an improvement in disease activity.
The ACR70 Improvement Criteria Response Rate From Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057	Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)	ACR70 represents at least 70% improvement from Baseline for each of TJC (68 joints) + SJC (66 joints) + at least 3 components of 5 for: PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: • TJC and SJC: same 2-point scale (0=absent;1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). • PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). • PAAP: 100 mm VAS (0=no pain;100=most severe pain). • HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. • CRP in mg/L. Missing values were considered as non-responding status.

Countries

Belgium, United Kingdom, United States

Participant flow

Recruitment details

The present study was an open-label extension to study RA0056 (NCT01242488). Subjects completing the 12-week treatment period of study RA0056 had the opportunity to participate in this study. First subject enrolled: 07 March 2011. Early termination: 05 Aug 2013.

Pre-assignment details

198 subjects completed the parent study RA0056 (NCT01242488); 190 subjects were enrolled in study RA0057. The study was a single treatment study and all subjects received CDP6038 (olokizumab) 120 mg sc q2w, however, some results are also presented according to the previously assigned treatment arms of the parent study RA0056.

Participants by arm

Arm	Count
RA0056 CDP6038 (Olokizumab) 120 mg q2w CDP6038 (olokizumab) 120 mg administered q2w sc in Study RA0056, and maintained at same dose (i.e. 120 mg q2w sc) at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	20
RA0056 CDP6038 (Olokizumab) 120 mg q4w CDP6038 (olokizumab) 120 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	20
RA0056 CDP6038 (Olokizumab) 240 mg q2w CDP6038 (olokizumab) 240 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	21
RA0056 CDP6038 (Olokizumab) 240 mg q4w CDP6038 (olokizumab) 240 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	20
RA0056 CDP6038 (Olokizumab) 60 mg q2w CDP6038 (olokizumab) 60 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	17
RA0056 CDP6038 (Olokizumab) 60 mg q4w CDP6038 (olokizumab) 60 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	16
RA0056 Placebo Placebo (sodium chloride, 0.9%) was administered q2w or q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	40
RA0056 Tocilizumab 8 mg/kg q4w Tocilizumab 8 mg/kg administered q4w iv in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.	36
Total	190

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Overall Study	Adverse Event	3	1	4	3	1	6	11	3
Overall Study	Continued elevated liver enzymes	0	0	0	1	0	0	0	0
Overall Study	Failure to comply with visits	0	0	0	0	0	0	0	1
Overall Study	Investigator discretion	0	0	0	0	0	0	1	0
Overall Study	Lack of Efficacy	1	4	1	1	1	0	2	3
Overall Study	Lost to Follow-up	0	0	1	1	2	0	4	2
Overall Study	Methotrexate discontinued	0	0	0	1	0	0	0	0
Overall Study	Ongoing missed appointments	0	0	0	0	0	0	1	0
Overall Study	Other	0	0	0	0	0	0	1	0
Overall Study	Patient decision due to transport	0	0	0	0	0	0	0	1
Overall Study	Protocol Violation	0	0	0	1	1	0	0	0
Overall Study	Required restricted steroid injections	0	0	0	0	0	0	1	0
Overall Study	Study termination	8	1	5	4	4	4	8	10
Overall Study	Withdrawal by Subject	4	2	2	1	1	1	2	1

Baseline characteristics

Characteristic	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	Total
Age, Customized <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized >=65 years	4 Participants	4 Participants	6 Participants	4 Participants	3 Participants	2 Participants	13 Participants	7 Participants	43 Participants
Age, Customized Between 18 and 65 years	16 Participants	17 Participants	14 Participants	13 Participants	17 Participants	14 Participants	27 Participants	29 Participants	147 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	3 Participants	2 Participants	1 Participants	1 Participants	4 Participants	3 Participants	4 Participants	19 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	4 Participants
Race (NIH/OMB) White	18 Participants	18 Participants	18 Participants	16 Participants	19 Participants	12 Participants	35 Participants	31 Participants	167 Participants
Sex: Female, Male Female	17 Participants	19 Participants	16 Participants	14 Participants	17 Participants	14 Participants	33 Participants	31 Participants	161 Participants
Sex: Female, Male Male	3 Participants	2 Participants	4 Participants	3 Participants	3 Participants	2 Participants	7 Participants	5 Participants	29 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 20	0 / 21	0 / 20	0 / 17	1 / 16	1 / 40	0 / 36
other Total, other adverse events	16 / 20	20 / 20	18 / 21	17 / 20	15 / 17	15 / 16	36 / 40	35 / 36
serious Total, serious adverse events	3 / 20	6 / 20	6 / 21	7 / 20	5 / 17	3 / 16	14 / 40	4 / 36

Outcome results

Primary

Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

Reported TEAEs included adverse events that started or worsened after the first dose of CDP6038 (olokizumab) in Study RA0057 and within 30 days after the last dose.

Time frame: From Baseline (Week 0 of Study RA0057) until 30 days after the last dose (maximum up to 780 days)

Population: Safety Population included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) in Study RA0057.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	17 Participants
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	20 Participants
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	19 Participants
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	18 Participants
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	15 Participants
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	15 Participants
RA0056 Placebo	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	39 Participants
RA0056 Tocilizumab 8 mg/kg q4w	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	35 Participants

Secondary

Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.

Time frame: Baseline (Week 0 of Study RA0056) and Week 24 (Study RA0057)

Population: FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057. When baseline and actual mean scores were not available, change from baseline was not calculated. Here, Number of Participants Analyzed included those participants who were evaluable for the assessment.

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.6441 units on a scale	Standard Deviation 1.46566
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	1.46566 units on a scale	Standard Deviation 1.17637
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.5811 units on a scale	Standard Deviation 1.40191
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.5999 units on a scale	Standard Deviation 1.16812
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-1.7189 units on a scale	Standard Deviation 0.87218
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.4221 units on a scale	Standard Deviation 1.37341
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.1484 units on a scale	Standard Deviation 1.34676
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057	-2.7624 units on a scale	Standard Deviation 1.47841

Secondary

Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057

Time frame: Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.3257 units on a scale	Standard Deviation 1.07427
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.2498 units on a scale	Standard Deviation 1.6658
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.5277 units on a scale	Standard Deviation 1.56763
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.7050 units on a scale	Standard Deviation 0.9616
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.3824 units on a scale	Standard Deviation 0.79065
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.1501 units on a scale	Standard Deviation 0.64141
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.2403 units on a scale	Standard Deviation 1.47765
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057	-2.7611 units on a scale	Standard Deviation 1.31329

Secondary

Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.

Time frame: Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-3.2427 units on a scale	Standard Deviation 1.74642
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-3.5767 units on a scale	—
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-2.5985 units on a scale	Standard Deviation 2.162
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-3.0999 units on a scale	Standard Deviation 0.02877
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-1.7516 units on a scale	Standard Deviation 2.03992
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-2.6451 units on a scale	Standard Deviation 0.96108
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-3.3173 units on a scale	Standard Deviation 3.23508
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057	-3.7982 units on a scale	Standard Deviation 1.23889

Secondary

Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057

CDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS and PhGADA-VAS, according to the following formula: SJC + TJC + PtGADA + PhGADA Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Total score range is from 0-100, with the high scores representing high disease activity. A negative change in CDAI score indicates an improvement in disease activity.

Time frame: Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-108.0000 units on a scale	Standard Deviation 66.77574
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-118.0000 units on a scale	—
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-89.0000 units on a scale	Standard Deviation 55.97321
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-74.3846 units on a scale	Standard Deviation 4.78657
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-74.0000 units on a scale	Standard Deviation 55.74944
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-90.5000 units on a scale	Standard Deviation 13.43503
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-104.5000 units on a scale	Standard Deviation 126.57211
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057	-107.4000 units on a scale	Standard Deviation 51.5296

Secondary

Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057

Time frame: Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-80.1000 units on a scale	Standard Deviation 53.28425
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-65.3373 units on a scale	Standard Deviation 63.72098
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-94.3335 units on a scale	Standard Deviation 61.48562
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-80.8077 units on a scale	Standard Deviation 57.91606
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-79.9231 units on a scale	Standard Deviation 30.09849
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-84.8378 units on a scale	Standard Deviation 33.77586
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-74.3315 units on a scale	Standard Deviation 53.99274
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057	-83.4950 units on a scale	Standard Deviation 42.48396

Secondary

Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057

DAS28(CRP) was calculated using the tender/painful joint count (TJC) and swollen joint count (SJC) from 28 joints, the Patient's Global Assessment of Disease Activity (PtGADA)-Visual Analog Scale (VAS), andCRP according to the formula: DAS28(CRP)=0.56 \* (TJC)\^1/2 + 0.28 \* (SJC)\^1/2 + 0.36 \* ln(CRP\[mg/L\]+1) + 0.014 \* PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity.

Time frame: Baseline (Week 0 of Study RA0056) and Week 12 (Study RA0057)

Population: Full Analysis Set (FAS) included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057. When baseline and actual mean scores were not available, change from baseline was not calculated. Here, Number of Participants Analyzed included those participants who were evaluable for the assessment.

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.2809 units on a scale	Standard Deviation 1.45737
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.2485 units on a scale	Standard Deviation 1.39384
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.5123 units on a scale	Standard Deviation 1.39667
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.2230 units on a scale	Standard Deviation 1.17572
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-1.6957 units on a scale	Standard Deviation 0.67335
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.1735 units on a scale	Standard Deviation 1.56606
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.3727 units on a scale	Standard Deviation 1.41421
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint Count (C-reactive Protein) (DAS28[CRP]) to Week 12 of Study RA0057	-2.4710 units on a scale	Standard Deviation 1.43947

Secondary

Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057

SDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS, PhGADA-VAS and CRP (in milligrams per decilitre \[mg/dL\]), according to the following formula: SJC + TJC + PtGADA + PhGADA + CRP (mg/dL) Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). • CRP range was from 0 to 10 mg/dL. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. A negative change in SDAI score indicates an improvement in disease activity.

Time frame: Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-111.0000 units on a scale	Standard Deviation 68.78953
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-125.0000 units on a scale	—
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-90.3333 units on a scale	Standard Deviation 56.0476
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-91.8846 units on a scale	Standard Deviation 29.53531
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-75.3333 units on a scale	Standard Deviation 56.09219
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-147.5000 units on a scale	Standard Deviation 77.07464
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-128.0000 units on a scale	Standard Deviation 147.07821
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057	-143.4000 units on a scale	Standard Deviation 80.28574

Secondary

Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057

Time frame: Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

Arm	Measure	Value (MEAN)	Dispersion
RA0056 CDP6038 (Olokizumab) 120 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-92.1000 units on a scale	Standard Deviation 62.22799
RA0056 CDP6038 (Olokizumab) 120 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-75.8757 units on a scale	Standard Deviation 74.37825
RA0056 CDP6038 (Olokizumab) 240 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-104.6668 units on a scale	Standard Deviation 80.47988
RA0056 CDP6038 (Olokizumab) 240 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-92.4077 units on a scale	Standard Deviation 55.42723
RA0056 CDP6038 (Olokizumab) 60 mg q2w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-87.7564 units on a scale	Standard Deviation 28.41084
RA0056 CDP6038 (Olokizumab) 60 mg q4w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-112.5378 units on a scale	Standard Deviation 52.99896
RA0056 Placebo	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-87.5815 units on a scale	Standard Deviation 59.26016
RA0056 Tocilizumab 8 mg/kg q4w	Change From Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057	-107.4080 units on a scale	Standard Deviation 60.17362

Secondary