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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002125-11 | EudraCT Number |
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This is a Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between CT-P13 SC and CT-P13 IV in Patients with Active Rheumatoid Arthritis (RA).
A new subcutaneous infliximab formulation is developed by Celltrion, Inc. as an alternative to the intravenous regimen where subcutaneous infliximab injection typically takes less than 2 minutes. The availability of a subcutaneous formulation of infliximab would increase the treatment options available to patients, particularly those wishing to self-administer their therapy. This Phase I/III Study randomized, double-blinded (Part 2 only), multicenter, parallel-group study was designed to evaluate Efficacy, Pharmacokinetics and Safety between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients with Active RA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: CT-P13 IV 3 mg/kg | Active Comparator | CT-P13 Intravenous (IV) (Infliximab), 3 mg/kg by IV infusion every 8 weeks (Part 1) |
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| Cohort 2: CT-P13 SC 90 mg | Experimental | CT-P13 Subcutaneous (SC) (Infliximab), 90 mg by SC injection every other week (Part 1) |
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| Cohort 3: CT-P13 SC 120 mg | Experimental | CT-P13 SC (Infliximab), 120 mg by SC injection every other week (Part 1) |
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| Cohort 4: CT-P13 SC 180 mg | Experimental | CT-P13 SC (Infliximab), 180 mg by SC injection every other week (Part 1) |
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| Arm 1: CT-P13 SC 120 mg | Experimental | CT-P13 SC (Infliximab), 120 mg by SC injection every other week with placebo intravenous infusion at Weeks 6, 14 and 22 (Part 2) |
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| Arm 2: CT-P13 IV 3 mg/kg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CT-P13 | Biological | CT-P13 (3 mg/kg) by IV infusion administered as a 2 hour IV infusion per dose every 8 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1) | For Part 1, the primary pharmacokinetic (PK) endpoint of the AUCτ (area under the concentration-time curve) at steady state between Week 22 and Week 30 was analyzed in patients who received all doses (full) of study drug up to Week 30 (prior to Week 30) in the PK population. All patients in SC cohorts were randomly assigned at Week 14 in a 1:1 ratio to either Group A or B for PK monitoring visit period (Week 22 and Week 30). Therefore, AUCτ was calculated at Week 22 for Cohort 1: CT-P13 IV 3 mg/kg, Weeks 22 and 26 for Group A of SC cohorts, and Weeks 24 and 28 for Group B of SC cohorts. | Weeks 22 (pre-dose to 216 hours post-dose), 24 (14 days after start of administration [SOA] at Week 22), 26 (pre-dose) and 28 (42 days after SOA at Week 22), and Week 30 (pre-dose) |
| Change From Baseline of Disease Activity Score Using 28 Joint Counts (DAS28) (CRP) at Week 22 (Part 2) | For Part 2, the primary efficacy endpoint was to demonstrate that CT-P13 SC 120 mg is non-inferior to CT-P13 IV 3 mg/kg at Week 22, as determined by clinical response according to mean change from baseline in DAS28 (CRP) at Week 22, using Analysis of Covariance (ANCOVA). Change from baseline for ANCOVA was defined as decrease from baseline and calculated as (DAS28 [CRP] at baseline - DAS28 [CRP] at Week 22). DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) equals(=) (0.56 multiplied by [*] the square root [√] of TJC28 [tender joint count]) plus (+) (0.28 * √ of SJC28 [swollen joint count]) + (0.36 * the natural logarithm [ln](CRP [mg/L] + 1)) + (0.014 * patient global disease activity [GH] on visual analogue assessment [VAS]) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity. | Week 22 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Actual Value of Disease Activity Score Using 28 Joint Counts (DAS28 [CRP]) (Part 2) | The secondary endpoint was defined as descriptive statistics of actual value in disease activity measured by DAS28 (CRP) up to Week 54. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV) in both treatment arms. DAS28 (CRP) was calculated according to the following formula: DAS28 (CRP) = (0.56* √ of TJC28) + (0.28 * √ of SJC28) + (0.36 * ln(CRP [mg/L] + 1)) + (0.014 * GH on VAS) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of the patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MoonSun Choi | Celltrion | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hanyang University Medical Center | Seoul | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36534825 | Derived | Constantin A, Caporali R, Edwards CJ, Fonseca JE, Iannone F, Keystone E, Schulze-Koops H, Kwon T, Kim S, Yoon S, Kim DH, Park G, Yoo DH. Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: a post-hoc analysis of a randomized phase III trial. Rheumatology (Oxford). 2023 Aug 1;62(8):2838-2844. doi: 10.1093/rheumatology/keac689. | |
| 33230526 |
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For Part 1, a total of 90 patients were screened, 50 patients were enrolled (40 screening failures) and 48 patients were randomized. For Part 2, a total of 528 patients were screened, 357 patients were enrolled and 343 patients were randomized. Of these, 5 patients from a significant GCP noncompliance site were excluded in all analysis population.
Participants recruited from 21 study centers in 8 countries for Part 1. Participants recruited from 76 study centers (including 1 good clinical practice [GCP] noncompliant study center) in 12 countries for Part 2. The study was divided into 2 parts (Part 1 and Part 2). Thus, the patients from Part 2 were newly enrolled/randomized only for Part 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: CT-P13 IV 3 mg/kg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received further 7 doses of CT-P13 IV 3 mg/kg (Infliximab) by IV infusion at Week 6 and every 8 weeks thereafter up to Week 54. Throughout the study, methotrexate (MTX) 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| FG001 | Cohort 2: CT-P13 SC 90 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 90 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6. The dose of SC 90 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 2: CT-P13 SC 90 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| FG002 | Cohort 3: CT-P13 SC 120 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6 up to Week 54. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| FG003 | Cohort 4: CT-P13 SC 180 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 180 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6. The dose of SC 180 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 4: CT-P13 SC 180 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| FG004 | Arm 1: CT-P13 SC 120 mg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6 up to Week 54 with placebo IV at Weeks 6, 14, and 22. Patients in specific countries were administered CT-P13 SC via auto injector (AI) at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| FG005 | Arm 2: CT-P13 IV 3 mg/kg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 IV 3 mg/kg (Infliximab) by IV infusion with a 8-week interval from Week 6 up to Week 22 (Weeks 6, 14 and 22) with placebo SC at Week 6 and every 2 weeks thereafter up to Week 28. CT-P13 IV were switched to receive CT-P13 SC via PFS at Week 30, and further doses with CT-P13 SC were given up to Week 54. Patients in specific countries were administered CT-P13 SC via AI at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All-randomized population consisted of all randomly assigned patients at Week 6, regardless of whether or not any study drug dosing was completed. All patients in the all-randomized population were analyzed according to the treatment they randomized to at Week 6.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: CT-P13 IV 3 mg/kg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received further 7 doses of CT-P13 IV 3 mg/kg (Infliximab) by IV infusion at Week 6 and every 8 weeks thereafter up to Week 54. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1) | For Part 1, the primary pharmacokinetic (PK) endpoint of the AUCτ (area under the concentration-time curve) at steady state between Week 22 and Week 30 was analyzed in patients who received all doses (full) of study drug up to Week 30 (prior to Week 30) in the PK population. All patients in SC cohorts were randomly assigned at Week 14 in a 1:1 ratio to either Group A or B for PK monitoring visit period (Week 22 and Week 30). Therefore, AUCτ was calculated at Week 22 for Cohort 1: CT-P13 IV 3 mg/kg, Weeks 22 and 26 for Group A of SC cohorts, and Weeks 24 and 28 for Group B of SC cohorts. | The PK population consisted of the all-randomized population who received at least 1 full dose of study drug at Week 6 or thereafter and who had at least 1 PK concentration result after Week 6 treatment. Among them, patients who had AUCτ result at steady state were included for the primary analysis. | Posted | Mean | Standard Deviation | hr*ng/mL | Weeks 22 (pre-dose to 216 hours post-dose), 24 (14 days after start of administration [SOA] at Week 22), 26 (pre-dose) and 28 (42 days after SOA at Week 22), and Week 30 (pre-dose) |
Adverse events (AEs) and serious adverse events (SAEs) were assessed from the date the informed consent form was signed until the last assessment date or End-of-Study (EOS) visit. The duration of the study was up to Week 62 for Part 1, and the study duration for Part 2 was up to Week 66 per country.
Investigator was responsible for reporting all AEs that were observed during the study regardless of their relationship to study drug/clinical significance. Safety analysis was pre-specified to only report the most severe event if the same events were occurred to the same patient. All patients who received at least 1 (partial or full) dose of study drug at Week 6 or thereafter were included in safety analysis. But, for Part 2, one patient in IV group was mis-randomized and analyzed as SC group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: CT-P13 IV 3 mg/kg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received further 7 doses of CT-P13 IV 3 mg/kg (Infliximab) by IV infusion at Week 6 and every 8 weeks thereafter up to Week 54. Throughout the study, methotrexate (MTX) 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
Study was divided into 2 parts; Part 1 was designed to find the optimal dose of CT-P13 SC with small number of patients (~13 patients in each cohort) and Part 2 was designed to demonstrate noninferiority of CT-P13 SC with large number of patients.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| SungHyun Kim | Celltrion. Inc. | +82 32 850 5778 | SungHyun.Kim@celltrion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 10, 2018 | Nov 26, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan (Part 2) | Mar 24, 2019 | Nov 26, 2019 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan Addendum (Part 2) | Jul 15, 2019 | Nov 26, 2019 | SAP_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan (Part 1) | Jun 26, 2018 | Nov 26, 2019 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C000591237 | CT-P13 |
| D000069285 | Infliximab |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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Part 1 was open label.
CT-P13 IV (Infliximab), 3 mg/kg by IV infusion every 8 weeks with placebo subcutaneous injection at Week 6 and every 2 weeks thereafter up to Week 28 (Part 2) |
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| CT-P13 | Biological | CT-P13 (90 mg) by single SC injection every other week |
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| CT-P13 | Biological | CT-P13 (120 mg) by single SC injection every other week |
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| CT-P13 | Biological | CT-P13 (180 mg) by double SC 90 mg injections every other week |
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| CT-P13 | Biological | CT-P13 (120 mg) by single SC injection every other week with placebo IV at Weeks 6, 14 and 22. |
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| CT-P13 | Biological | CT-P13 (3 mg/kg) by IV infusion administered as a 2 hour IV infusion per dose every 8 weeks with placebo SC at Week 6 and every other week thereafter up to Week 28 |
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| Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54 |
| Number of Patients Achieving Clinical Response According to American College of Rheumatology 20% Response (ACR20) (Part 2) | The secondary endpoint was defined as number of patients achieving clinical response according to ACR20 (20% response, defined by ACR) between CT-P13 SC and CT-P13 IV groups. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV). Responder according to the ACR20 criteria defined as, if they are fulfilled, a decrease of at least 20% in number of tender joints and swollen joints (0-28), and 20% improvement in 3 of the followings: patient assessment of pain on VAS (0-100 mm), patient global assessment of disease activity on VAS (0-100 mm) and physician global assessment of disease activity on VAS (0-100 mm), health assessment questionnaire disability index and CRP or ESR (erythrocyte sedimentation rate). | Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54 |
| Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2) | For evaluation of pharmacokinetics (PK), the secondary endpoint was defined as the analysis of trough concentration (concentration before the next study drug administration) of Infliximab up to Week 54. The samples were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. During PK monitoring visit (Weeks 22-30), samples were collected every 2 weeks according steady state PK sampling time point. All patients were randomly assigned at Week 14 in a 1:1:1:1 ratio to one of 4 groups (Groups A, B, C or D) for PK monitoring visit period. No PK results were obtained at Weeks 6 and 14 for SC group and Weeks 12, 20, 24, 26 and 28 for IV group due to 2 weeks and 8 weeks dosing interval, respectively. | SC group: Weeks 0, 2, 12, 20, 22, 24, 26, 28, 36, 44, and 52; IV group: Weeks 0, 2, 6, 14, 22, 36, 44, and 52 |
| Mean Actual Value in Serum CRP Concentration (Pharmacodynamic Parameter) (Part 2) | For evaluation of pharmacodynamic (PD), the secondary endpoint was defined as concentration of CRP between 2 treatment groups up to Week 54. The blood samples for CRP were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. Patient who received the other treatment than that to which they were assigned at any point was defined as mis-randomized. One patient in IV group was mis-randomized and analyzed as SC group for PD analysis. | Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, and Week 54 |
| Westhovens R, Wiland P, Zawadzki M, Ivanova D, Kasay AB, El-Khouri EC, Balazs E, Shevchuk S, Eliseeva L, Stanislavchuk M, Yatsyshyn R, Hrycaj P, Jaworski J, Zhdan V, Trefler J, Shesternya P, Lee SJ, Kim SH, Suh JH, Lee SG, Han NR, Yoo DH. Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial. Rheumatology (Oxford). 2021 May 14;60(5):2277-2287. doi: 10.1093/rheumatology/keaa580. |
| Disease progression |
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| Withdrawal by Subject |
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| Protocol Violation |
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| Lost to Follow-up |
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| Pregnancy |
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| Death |
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| Physician Decision |
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| Prolonged Dosing Interval |
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| BG001 | Cohort 2: CT-P13 SC 90 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 90 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6. The dose of SC 90 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 2: CT-P13 SC 90 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| BG002 | Cohort 3: CT-P13 SC 120 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6 up to Week 54. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| BG003 | Cohort 4: CT-P13 SC 180 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 180 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6. The dose of SC 180 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 4: CT-P13 SC 180 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| BG004 | Arm 1: CT-P13 SC 120 mg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6 up to Week 54 with placebo IV at Weeks 6, 14, and 22. Patients in specific countries were administered CT-P13 SC via AI at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| BG005 | Arm 2: CT-P13 IV 3 mg/kg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 IV 3 mg/kg (Infliximab) by IV infusion with a 8-week interval from Week 6 up to Week 22 (Weeks 6, 14 and 22) with placebo SC at Week 6 and every 2 weeks thereafter up to Week 28. CT-P13 IV were switched to receive CT-P13 SC via PFS at Week 30, and further doses with CT-P13 SC were given up to Week 54. Patients in specific countries were administered CT-P13 SC via AI at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| BG006 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ID | Title | Description |
|---|
| OG000 | Cohort 1: CT-P13 IV 3 mg/kg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received further 7 doses of CT-P13 IV 3 mg/kg (Infliximab) by IV infusion at Week 6 and every 8 weeks thereafter up to Week 54. Throughout the study, methotrexate (MTX) 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| OG001 | Cohort 2: CT-P13 SC 90 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 90 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6. The dose of SC 90 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 2: CT-P13 SC 90 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| OG002 | Cohort 3: CT-P13 SC 120 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6 up to Week 54. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
| OG003 | Cohort 4: CT-P13 SC 180 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 180 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6. The dose of SC 180 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 4: CT-P13 SC 180 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. |
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| Primary | Change From Baseline of Disease Activity Score Using 28 Joint Counts (DAS28) (CRP) at Week 22 (Part 2) | For Part 2, the primary efficacy endpoint was to demonstrate that CT-P13 SC 120 mg is non-inferior to CT-P13 IV 3 mg/kg at Week 22, as determined by clinical response according to mean change from baseline in DAS28 (CRP) at Week 22, using Analysis of Covariance (ANCOVA). Change from baseline for ANCOVA was defined as decrease from baseline and calculated as (DAS28 [CRP] at baseline - DAS28 [CRP] at Week 22). DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) equals(=) (0.56 multiplied by [*] the square root [√] of TJC28 [tender joint count]) plus (+) (0.28 * √ of SJC28 [swollen joint count]) + (0.36 * the natural logarithm [ln](CRP [mg/L] + 1)) + (0.014 * patient global disease activity [GH] on visual analogue assessment [VAS]) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity. | Efficacy population consisted of all randomly assigned patients who received at least 1 full dose of study drug at Week 6 or thereafter and had at least 1 efficacy result after Week 6. Among them, patients who had DAS28 (CRP) at Week 22 were included for the analysis. All patients were analyzed according to the treatment they received. | Posted | Least Squares Mean | Standard Error | score on a scale | Week 22 |
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| Secondary | Mean Actual Value of Disease Activity Score Using 28 Joint Counts (DAS28 [CRP]) (Part 2) | The secondary endpoint was defined as descriptive statistics of actual value in disease activity measured by DAS28 (CRP) up to Week 54. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV) in both treatment arms. DAS28 (CRP) was calculated according to the following formula: DAS28 (CRP) = (0.56* √ of TJC28) + (0.28 * √ of SJC28) + (0.36 * ln(CRP [mg/L] + 1)) + (0.014 * GH on VAS) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of the patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity. | The efficacy population consisted of all randomly assigned patients who received at least 1 full dose of study drug (CT-P13 IV or CT-P13 SC) at Week 6 or thereafter, and who had at least 1 efficacy evaluation result after Week 6 and thereafter treatment. All patients in efficacy population were analyzed according to the treatment they received. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54 |
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| Secondary | Number of Patients Achieving Clinical Response According to American College of Rheumatology 20% Response (ACR20) (Part 2) | The secondary endpoint was defined as number of patients achieving clinical response according to ACR20 (20% response, defined by ACR) between CT-P13 SC and CT-P13 IV groups. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV). Responder according to the ACR20 criteria defined as, if they are fulfilled, a decrease of at least 20% in number of tender joints and swollen joints (0-28), and 20% improvement in 3 of the followings: patient assessment of pain on VAS (0-100 mm), patient global assessment of disease activity on VAS (0-100 mm) and physician global assessment of disease activity on VAS (0-100 mm), health assessment questionnaire disability index and CRP or ESR (erythrocyte sedimentation rate). | The efficacy population consisted of all randomly assigned patients who received at least 1 full dose of study drug (CT-P13 IV or CT-P13 SC) at Week 6 or thereafter, and who had at least 1 efficacy evaluation result after Week 6 and thereafter treatment. All patients in efficacy population were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54 |
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| Secondary | Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2) | For evaluation of pharmacokinetics (PK), the secondary endpoint was defined as the analysis of trough concentration (concentration before the next study drug administration) of Infliximab up to Week 54. The samples were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. During PK monitoring visit (Weeks 22-30), samples were collected every 2 weeks according steady state PK sampling time point. All patients were randomly assigned at Week 14 in a 1:1:1:1 ratio to one of 4 groups (Groups A, B, C or D) for PK monitoring visit period. No PK results were obtained at Weeks 6 and 14 for SC group and Weeks 12, 20, 24, 26 and 28 for IV group due to 2 weeks and 8 weeks dosing interval, respectively. | The PK population consisted of all randomly assigned patients who received at least 1 full dose of study drug (CT-P13 IV, CT-P13 SC) at Week 6 or thereafter and who had at least 1 PK concentration result after Week 6 or thereafter treatment. All patients in PK population were analyzed according to the treatment they received. | Posted | Mean | Standard Deviation | μg/mL | SC group: Weeks 0, 2, 12, 20, 22, 24, 26, 28, 36, 44, and 52; IV group: Weeks 0, 2, 6, 14, 22, 36, 44, and 52 |
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| Secondary | Mean Actual Value in Serum CRP Concentration (Pharmacodynamic Parameter) (Part 2) | For evaluation of pharmacodynamic (PD), the secondary endpoint was defined as concentration of CRP between 2 treatment groups up to Week 54. The blood samples for CRP were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. Patient who received the other treatment than that to which they were assigned at any point was defined as mis-randomized. One patient in IV group was mis-randomized and analyzed as SC group for PD analysis. | The PD population consisted of all randomized population who received at least 1 full dose of study drug at Week 6 or thereafter and had at least 1 PD result (rheumatoid factor, anti-cyclic citrullinated peptide, CRP or ESR) after Week 6 treatment. All patients in PD population were analyzed according to the treatment they received. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, and Week 54 |
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|
|
| 0 |
| 13 |
| 1 |
| 13 |
| 8 |
| 13 |
| EG001 | Cohort 2: CT-P13 SC 90 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 90 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6. The dose of SC 90 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 2: CT-P13 SC 90 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. | 0 | 11 | 2 | 11 | 7 | 11 |
| EG002 | Cohort 3: CT-P13 SC 120 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6 up to Week 54. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. | 0 | 12 | 0 | 12 | 8 | 12 |
| EG003 | Cohort 4: CT-P13 SC 180 mg (Part 1) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 180 mg (Infliximab) by SC injection via PFS with a 2-week interval from Week 6. The dose of SC 180 mg was adjusted to SC 120 mg every 2 weeks after Week 30 in applicable patients in Cohort 4: CT-P13 SC 180 mg. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. | 0 | 12 | 3 | 12 | 9 | 12 |
| EG004 | Arm 1: CT-P13 SC 120 mg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 SC 120 mg (Infliximab) by SC injection via pre-filled syringe (PFS) with a 2-week interval from Week 6 up to Week 54 with placebo IV at Weeks 6, 14, and 22. Patients in specific countries were administered CT-P13 SC via auto injector (AI) at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. | 1 | 168 | 6 | 168 | 91 | 168 |
| EG005 | Arm 2: CT-P13 IV 3 mg/kg (Part 2) | Each participant received 2 CT-P13 IV infusions with a 2-week interval at Weeks 0 and 2. Then, this group received CT-P13 IV 3 mg/kg (Infliximab) by IV infusion with a 8-week interval from Week 6 up to Week 22 (Weeks 6, 14 and 22) with placebo SC at Week 6 and every 2 weeks thereafter up to Week 28. CT-P13 IV were switched to receive CT-P13 SC via PFS at Week 30, and further doses with CT-P13 SC were given up to Week 54. Patients in specific countries were administered CT-P13 SC via AI at Week 46 and every 2 weeks thereafter up to Week 54, and patients were switched back to CT-P13 SC via PFS at Week 56 and every 2 weeks thereafter up to Week 64. Throughout the study, MTX 12.5 to 25 mg/week (between 10 to 25 mg/week in Korea), oral and parenteral dose and folic acid (≥ 5 mg/week) were coadministered, oral dose. | 4 | 175 | 14 | 175 | 90 | 175 |
| Atrial fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
| Hereditary haemochromatosis | Congenital, familial and genetic disorders | MedDRA (20.0) | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA (20.0) | Systematic Assessment |
|
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Inguinal hernia | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA (20.0) | Systematic Assessment | General disorders and administration site conditions |
|
| Influenza | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Pertussis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Tracheobronchitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment | Preferred term reported as administration related reaction and occurred between start of administration and 24 hours from the end of IV infusion (including placebo for Part 2) |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dementia Alzheimer's type | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Device loosening | Product Issues | MedDRA (20.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Antiphospholipid syndrome | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Latent tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Pulmonary tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Localized injection site reaction | General disorders | MedDRA (20.0) | Systematic Assessment | General disorders and administration site conditions; preferred term reported as injection site reaction |
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| Bronchitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Latent tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment | Infusion related reaction occurred between start of administration and 24 hours from the end of IV infusion (including placebo for Part 2) |
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| Alanine aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
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| Middle ear inflammation | Ear and labyrinth disorders | MedDRA (20.0) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA (20.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment |
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| Angular cheilitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Otosalpingitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Vaginal infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
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| Spinal fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
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| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
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| Systemic injection reaction | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment | Systemic injection reaction occurred between start of administration and 24 hours from the SC injection (including placebo for Part 2) |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Electrocardiogram abnormal | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Glucose urine | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Transaminases increased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (20.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Radiculopathy | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
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| Cervical polyp | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Beta-2 glycoprotein antibody positive | Investigations | MedDRA (20.0) | Systematic Assessment |
|
| Delayed hypersensitivity | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment | Delayed hypersensitivity occurred after 24 hours from the study drug administration |
|
Not provided
Not provided
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
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| Week 22 |
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| Week 54 |
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| Week 14 |
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| Week 22 |
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| Week 30 |
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| Week 54 |
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| Week 2 |
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| Week 6 |
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| Week 12 |
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| Week 14 |
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| Week 20 |
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| Week 22 |
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| Week 24 |
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| Week 26 |
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| Week 28 |
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| Week 36 |
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| Week 44 |
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| Week 52 |
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| Week 2 |
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| Week 6 |
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| Week 14 |
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| Week 22 |
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| Week 30 |
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| Week 38 |
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| Week 46 |
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| Week 54 |
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