Rheumatoid Arthritis
Conditions
Brief summary
This is a phase 3 study to compare efficacy and safety of CT-P47 and RoActemra in patients with moderate to severe active rheumatoid arthritis.
Detailed description
CT-P47, containing the active ingredient tocilizumab, is a recombinant humanized monoclonal antibody that is being developed as a similar biological medicinal product to RoActemra/Actemra. The purpose of this study is to demonstrate similar efficacy and safety of CT-P47 and RoActemra in patients with moderate to severe rheumatoid arthritis when co-administered with methotrexate.
Interventions
BIOLOGICALCT-P47
CT-P47, 8 mg/kg (not exceeding 800 mg/dose) by intravenous (IV) infusion every 4 weeks (Q4W)
BIOLOGICALEU-approved RoActemra
EU-approved RoActemra, 8 mg/kg (not exceeding 800 mg/dose) by IV infusion Q4W
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patient is male or female aged 18 to 75 years old, both inclusive. 2. Patient has had a diagnosis of RA according to the 2010 ACR/EULAR classification criteria for at least 24 weeks prior to the first administration of the study drug.
Exclusion criteria
1. Patient who has previously received investigational or licensed product; targeted synthetic DMARD(s) (e.g., tofacitinib, baricitinib) for the treatment of RA and/or an interleukin-6 (IL-6) inhibitor for any purposes. 2. Patient who has previously received more than 1 biologic agents approved for the treatment of RA. 3. Patient who has allergies to any of the excipients of study drug or any other murine and human proteins, or patient with a hypersensitivity to immunoglobulin products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Disease Activity Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) at Week 24 | Week 24 | The DAS28(ESR) score was derived using the following formulae: DAS28 (ESR)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.70 × ln\[ESR\])+(0.014 ×GH) Where: * TJC28 = number of tender joints (0-28): tender joint count (TJC) * SJC28 = number of swollen joints (0-28): swollen joint count (SJC) * ESR = ESR measurement (mm/hour) * GH = patient's global disease activity measured on VAS (mm: 0-100) DAS28 (ESR) values could be ranged from 0 to 10 while higher values mean a higher disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in DAS28 (ESR) at Week 32 | Week 32 | The DAS28(ESR) score was derived using the following formulae: DAS28 (ESR)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.70 × ln\[ESR\])+(0.014 ×GH) Where: * TJC28 = number of tender joints (0-28): tender joint count (TJC) * SJC28 = number of swollen joints (0-28): swollen joint count (SJC) * ESR = ESR measurement (mm/hour) * GH = patient's global disease activity measured on VAS (mm: 0-100) DAS28 (ESR) values could be ranged from 0 to 10 while higher values mean a higher disease activity. |
| ACR20, ACR50, and ACR70 Response Rate at Week 24 | Week 24 | ACR20 is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in the three of the following five criteria: 1) patient global assessment of disease activity, 2) physician global assessment of disease activity, 3) functional ability measure using Health Assessment Questionnaire (HAQ), 4) visual analog pain scale, and 5) erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ACR50 and ACR70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20. |
| ACR20, ACR50, and ACR70 Response Rate at Week 32 | Week 32 | ACR20 is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in the three of the following five criteria: 1) patient global assessment of disease activity, 2) physician global assessment of disease activity, 3) functional ability measure using Health Assessment Questionnaire (HAQ), 4) visual analog pain scale, and 5) erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ACR50 and ACR70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20. |
Countries
Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CT-P47 Patients who were initially randomly assigned to CT-P47 in Treatment Period I. | 234 |
| RoActemra Patients who were initially randomly assigned to RoActemra in Treatment Period I. | 237 |
| Total | 471 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period I | Adverse Event | 3 | 11 | 0 |
| Treatment Period I | Lost to Follow-up | 0 | 1 | 0 |
| Treatment Period I | Physician Decision | 0 | 1 | 0 |
| Treatment Period I | Withdrawal by Subject | 6 | 5 | 0 |
| Treatment Period II up to Week 32 | Adverse Event | 3 | 0 | 1 |
| Treatment Period II up to Week 32 | Ongoing | 222 | 107 | 107 |
| Treatment Period II up to Week 32 | Withdrawal by Subject | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | CT-P47 | RoActemra | Total |
|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 10.98 | 54.4 years STANDARD_DEVIATION 11.61 | 54.8 years STANDARD_DEVIATION 11.3 |
| Body Weight on Day 1 <100 kg | 208 Participants | 210 Participants | 418 Participants |
| Body Weight on Day 1 ≥100 kg | 26 Participants | 27 Participants | 53 Participants |
| DAS28 (ESR) score at Screening DAS28 (ESR) ≤5.1 | 5 Participants | 7 Participants | 12 Participants |
| DAS28 (ESR) score at Screening DAS28 (ESR) >5.1 | 229 Participants | 230 Participants | 459 Participants |
| Prior biologic use approved for RA treatment No | 176 Participants | 175 Participants | 351 Participants |
| Prior biologic use approved for RA treatment Yes | 58 Participants | 62 Participants | 120 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic or Non-Latino | 228 Participants | 233 Participants | 461 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 234 Participants | 237 Participants | 471 Participants |
| Sex: Female, Male Female | 181 Participants | 180 Participants | 361 Participants |
| Sex: Female, Male Male | 53 Participants | 57 Participants | 110 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 234 | 0 / 237 | 1 / 225 | 0 / 109 | 0 / 110 |
| other Total, other adverse events | 140 / 234 | 143 / 237 | 54 / 225 | 26 / 109 | 23 / 110 |
| serious Total, serious adverse events | 10 / 234 | 9 / 237 | 4 / 225 | 3 / 109 | 2 / 110 |
Outcome results
Primary
Mean Change From Baseline in Disease Activity Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) at Week 24
The DAS28(ESR) score was derived using the following formulae: DAS28 (ESR)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.70 × ln\[ESR\])+(0.014 ×GH) Where: * TJC28 = number of tender joints (0-28): tender joint count (TJC) * SJC28 = number of swollen joints (0-28): swollen joint count (SJC) * ESR = ESR measurement (mm/hour) * GH = patient's global disease activity measured on VAS (mm: 0-100) DAS28 (ESR) values could be ranged from 0 to 10 while higher values mean a higher disease activity.
Time frame: Week 24
Population: ITT set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CT-P47 | Mean Change From Baseline in Disease Activity Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) at Week 24 | -3.77 units on a scale | Standard Error 0.12 |
| RoActemra | Mean Change From Baseline in Disease Activity Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) at Week 24 | -3.67 units on a scale | Standard Error 0.118 |
90% CI: [-0.3, 0.1]ANCOVA
Secondary
ACR20, ACR50, and ACR70 Response Rate at Week 24
ACR20 is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in the three of the following five criteria: 1) patient global assessment of disease activity, 2) physician global assessment of disease activity, 3) functional ability measure using Health Assessment Questionnaire (HAQ), 4) visual analog pain scale, and 5) erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ACR50 and ACR70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20.
Time frame: Week 24
Population: ITT set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR20 | 199 Participants |
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR50 | 142 Participants |
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR70 | 100 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR20 | 189 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR50 | 146 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 24 | ACR70 | 99 Participants |
Secondary
ACR20, ACR50, and ACR70 Response Rate at Week 32
ACR20 is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in the three of the following five criteria: 1) patient global assessment of disease activity, 2) physician global assessment of disease activity, 3) functional ability measure using Health Assessment Questionnaire (HAQ), 4) visual analog pain scale, and 5) erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ACR50 and ACR70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20.
Time frame: Week 32
Population: ITT-Treatment Period II Subset
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR50 | 148 Participants |
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR20 | 199 Participants |
| CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR70 | 91 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR50 | 79 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR20 | 96 Participants |
| RoActemra | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR70 | 47 Participants |
| Switched to CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR20 | 98 Participants |
| Switched to CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR70 | 61 Participants |
| Switched to CT-P47 | ACR20, ACR50, and ACR70 Response Rate at Week 32 | ACR50 | 77 Participants |
Secondary
Mean Change From Baseline in DAS28 (ESR) at Week 32
The DAS28(ESR) score was derived using the following formulae: DAS28 (ESR)=(0.56 ×√TJC28)+(0.28 × √SJC28)+(0.70 × ln\[ESR\])+(0.014 ×GH) Where: * TJC28 = number of tender joints (0-28): tender joint count (TJC) * SJC28 = number of swollen joints (0-28): swollen joint count (SJC) * ESR = ESR measurement (mm/hour) * GH = patient's global disease activity measured on VAS (mm: 0-100) DAS28 (ESR) values could be ranged from 0 to 10 while higher values mean a higher disease activity.
Time frame: Week 32
Population: ITT-Treatment Period II Subset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P47 | Mean Change From Baseline in DAS28 (ESR) at Week 32 | -3.921 units on a scale | Standard Deviation 1.2548 |
| RoActemra | Mean Change From Baseline in DAS28 (ESR) at Week 32 | -3.994 units on a scale | Standard Deviation 1.1753 |
| Switched to CT-P47 | Mean Change From Baseline in DAS28 (ESR) at Week 32 | -4.218 units on a scale | Standard Deviation 1.138 |