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A Phase I/III Study to Evaluate Efficacy, PK and Safety Between CT-P13 SC and CT-P13 IV in Patients With Active RA

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ClinicalTrials.gov Identifier: NCT03147248
Recruitment Status : Completed
First Posted : May 10, 2017
Results First Posted : April 8, 2020
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Celltrion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Intervention Biological: CT-P13
Enrollment 407
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description 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. 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. 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. 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. 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. 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.
Period Title: Overall Study
Started 13 [1] 11 [1] 12 [1] 12 [1] 167 [2] 176 [2]
Completed 12 9 10 10 141 145
Not Completed 1 2 2 2 26 31
Reason Not Completed
Adverse Event             0             2             2             2             6             11
Disease progression             1             0             0             0             0             2
Withdrawal by Subject             0             0             0             0             12             9
Protocol Violation             0             0             0             0             2             0
Lost to Follow-up             0             0             0             0             2             0
Pregnancy             0             0             0             0             1             0
Death             0             0             0             0             0             4
Physician Decision             0             0             0             0             2             4
Prolonged Dosing Interval             0             0             0             0             1             1
[1]
This cohort is only for Part 1.
[2]
This arm is for Part 2. All of the participants in Part 2 were screened only for Part 2.
Arm/Group Title Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2) Total
Hide Arm/Group Description 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. 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. 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. 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.

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.

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. Total of all reporting groups
Overall Number of Baseline Participants 13 11 12 12 167 176 391
Hide Baseline Analysis Population Description
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.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 12 participants 12 participants 167 participants 176 participants 391 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.3%
Between 18 and 65 years
12
  92.3%
9
  81.8%
10
  83.3%
10
  83.3%
148
  88.6%
147
  83.5%
336
  85.9%
>=65 years
1
   7.7%
2
  18.2%
2
  16.7%
2
  16.7%
19
  11.4%
28
  15.9%
54
  13.8%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants 11 participants 12 participants 12 participants 167 participants 176 participants 391 participants
40.0
(24 to 69)
56.0
(39 to 68)
49.5
(30 to 65)
51.5
(32 to 68)
52.0
(19 to 74)
53.0
(18 to 74)
53.0
(18 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 12 participants 12 participants 167 participants 176 participants 391 participants
Female
11
  84.6%
9
  81.8%
9
  75.0%
9
  75.0%
130
  77.8%
139
  79.0%
307
  78.5%
Male
2
  15.4%
2
  18.2%
3
  25.0%
3
  25.0%
37
  22.2%
37
  21.0%
84
  21.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 12 participants 12 participants 167 participants 176 participants 391 participants
Asian/Oriental
0
   0.0%
0
   0.0%
1
   8.3%
1
   8.3%
1
   0.6%
2
   1.1%
5
   1.3%
White/Caucasian
13
 100.0%
11
 100.0%
11
  91.7%
11
  91.7%
145
  86.8%
151
  85.8%
342
  87.5%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
21
  12.6%
23
  13.1%
44
  11.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 12 participants 12 participants 167 participants 176 participants 391 participants
Bosnia and Herzegovina 0 0 0 0 10 11 21
Bulgaria 2 3 2 2 11 9 20
Chile 0 0 0 0 4 4 8
Estonia 2 1 1 2 0 3 3
Hungary 1 0 0 0 6 6 12
South Korea 0 0 1 1 1 2 3
Latvia 0 0 1 1 0 2 2
Peru 0 0 0 0 21 23 44
Poland 5 6 6 5 46 46 92
Russia 0 0 0 0 39 39 78
Spain 0 0 0 0 2 2 4
Ukraine 3 1 1 1 27 29 56
1.Primary Outcome
Title Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1)
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 13 10 11 12
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
Week 22 Number Analyzed 13 participants 5 participants 5 participants 6 participants
12032957.5  (5345598.59) 5047724.2  (2449771.86) 7333767.0  (2765064.19) 9930696.6  (3208367.37)
Week 24 Number Analyzed 0 participants 5 participants 6 participants 6 participants
3272936.8  (2847811.60) 4835631.9  (2156587.25) 9322764.3  (2704651.44)
Week 26 Number Analyzed 0 participants 5 participants 5 participants 6 participants
4722645.2  (2434832.19) 7295570.5  (2261574.63) 10402980.9  (3316415.11)
Week 28 Number Analyzed 0 participants 5 participants 6 participants 6 participants
3231316.6  (2582286.88) 5076458.7  (2733359.45) 10578411.8  (3443240.82)
2.Primary Outcome
Title Change From Baseline of Disease Activity Score Using 28 Joint Counts (DAS28) (CRP) at Week 22 (Part 2)
Hide Description 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.
Time Frame Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 162 168
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
2.21  (0.221) 1.94  (0.209)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1: CT-P13 SC 120 mg (Part 2), Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Comments Primary efficacy analysis were analyzed using an ANCOVA considering the treatment as fixed effect and country, serum CRP concentration at Week 2 (≤0.6 mg/dL vs. >0.6 mg/dL), and body weight at Week 6 (≤100 kg vs. >100 kg) as covariates.
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was to be concluded if the lower limit of the two-sided 95% confidence interval (CI) for the difference in the mean change from baseline of DAS28 (CRP) at Week 22 was greater that the pre-specified non-inferiority margin of -0.6.
Method of Estimation Estimation Parameter Difference of Least square mean
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
0.02 to 0.52
Estimation Comments The least squares means and standard errors, estimate of treatment difference (CT-P13 SC 120 mg - CT-P13 IV 3 mg/kg), and 2-sided 95% CI obtained from the ANCOVA model.
3.Secondary Outcome
Title Mean Actual Value of Disease Activity Score Using 28 Joint Counts (DAS28 [CRP]) (Part 2)
Hide Description 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.
Time Frame Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 165 174
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 165 participants 174 participants
6.0  (0.75) 5.9  (0.81)
Week 2 Number Analyzed 164 participants 172 participants
4.7  (0.94) 4.6  (1.05)
Week 6 Number Analyzed 165 participants 174 participants
4.0  (1.20) 4.1  (1.21)
Week 14 Number Analyzed 164 participants 172 participants
3.5  (1.20) 3.7  (1.25)
Week 22 Number Analyzed 162 participants 168 participants
3.3  (1.10) 3.5  (1.23)
Week 30 Number Analyzed 157 participants 159 participants
3.0  (1.13) 3.5  (1.23)
Week 54 Number Analyzed 145 participants 145 participants
2.8  (1.14) 2.9  (1.16)
4.Secondary Outcome
Title Number of Patients Achieving Clinical Response According to American College of Rheumatology 20% Response (ACR20) (Part 2)
Hide Description

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).

Time Frame Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 165 174
Measure Type: Count of Participants
Unit of Measure: Participants
Week 2
63
  38.2%
57
  32.8%
Week 6
107
  64.8%
103
  59.2%
Week 14
124
  75.2%
130
  74.7%
Week 22
139
  84.2%
137
  78.7%
Week 30
142
  86.1%
133
  76.4%
Week 54
132
  80.0%
125
  71.8%
5.Secondary Outcome
Title Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2)
Hide Description 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.
Time Frame 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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Hide Analysis Population Description
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.
Arm/Group Title Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 166 174
Mean (Standard Deviation)
Unit of Measure: μg/mL
Week 0 Number Analyzed 166 participants 174 participants
15.73  (5.83) 16.00  (5.99)
Week 2 Number Analyzed 166 participants 174 participants
8.64  (5.97) 8.81  (7.13)
Week 6 Number Analyzed 0 participants 172 participants
1.89  (2.61)
Week 12 Number Analyzed 165 participants 0 participants
12.33  (8.20)
Week 14 Number Analyzed 0 participants 164 participants
3.20  (11.14)
Week 20 Number Analyzed 159 participants 0 participants
12.72  (9.13)
Week 22 Number Analyzed 42 participants 156 participants
13.19  (10.57) 1.03  (1.85)
Week 24 Number Analyzed 41 participants 0 participants
12.32  (8.55)
Week 26 Number Analyzed 40 participants 0 participants
10.73  (7.08)
Week 28 Number Analyzed 152 participants 0 participants
12.27  (9.75)
Week 36 Number Analyzed 156 participants 150 participants
12.20  (9.44) 8.79  (8.63)
Week 44 Number Analyzed 150 participants 149 participants
11.24  (8.51) 9.97  (9.65)
Week 52 Number Analyzed 146 participants 147 participants
10.98  (8.81) 10.23  (10.08)
6.Secondary Outcome
Title Mean Actual Value in Serum CRP Concentration (Pharmacodynamic Parameter) (Part 2)
Hide Description

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.

Time Frame Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, and Week 54
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Hide Analysis Population Description
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.
Arm/Group Title Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 168 175
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Number Analyzed 168 participants 175 participants
1.82  (2.37) 2.23  (3.52)
Week 2 Number Analyzed 167 participants 173 participants
0.47  (0.78) 0.62  (1.43)
Week 6 Number Analyzed 168 participants 175 participants
0.74  (1.38) 0.98  (1.84)
Week 14 Number Analyzed 166 participants 173 participants
0.81  (1.96) 1.14  (2.53)
Week 22 Number Analyzed 163 participants 169 participants
0.72  (1.33) 1.16  (2.13)
Week 30 Number Analyzed 158 participants 160 participants
0.67  (1.26) 1.17  (2.14)
Week 38 Number Analyzed 158 participants 151 participants
0.71  (1.28) 1.08  (2.95)
Week 46 Number Analyzed 151 participants 148 participants
0.60  (1.01) 0.79  (1.47)
Week 54 Number Analyzed 146 participants 146 participants
0.60  (1.01) 0.78  (1.48)
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Hide Arm/Group Description 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. 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. 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. 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. 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. 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.
All-Cause Mortality
Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/11 (0.00%)   0/12 (0.00%)   0/12 (0.00%)   1/168 (0.60%)   4/175 (2.29%) 
Hide Serious Adverse Events
Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/13 (7.69%)   2/11 (18.18%)   0/12 (0.00%)   3/12 (25.00%)   6/168 (3.57%)   14/175 (8.00%) 
Blood and lymphatic system disorders             
Neutropenia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Antiphospholipid syndrome  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Cardiac disorders             
Atrial fibrillation  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Cardiac arrest  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Myocardial infarction  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  2/175 (1.14%) 
Congenital, familial and genetic disorders             
Hereditary haemochromatosis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Ear and labyrinth disorders             
Vertigo positional  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  2/175 (1.14%) 
Gastrointestinal disorders             
Duodenal ulcer haemorrhage  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Inguinal hernia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
General disorders             
Sudden death  1 [1]  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Infections and infestations             
Influenza  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Pertussis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Pneumonia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  2/168 (1.19%)  0/175 (0.00%) 
Tracheobronchitis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Latent tuberculosis  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Pulmonary tuberculosis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Urinary tract infection  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Injury, poisoning and procedural complications             
Infusion related reaction  1 [2]  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Hip fracture  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Spinal compression fracture  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Spinal osteoarthritis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Intervertebral disc disorder  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Nervous system disorders             
Cerebral infarction  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Dementia Alzheimer's type  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Product Issues             
Device loosening  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Vascular disorders             
Deep vein thrombosis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
[1]
General disorders and administration site conditions
[2]
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)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Cohort 1: CT-P13 IV 3 mg/kg (Part 1) Cohort 2: CT-P13 SC 90 mg (Part 1) Cohort 3: CT-P13 SC 120 mg (Part 1) Cohort 4: CT-P13 SC 180 mg (Part 1) Arm 1: CT-P13 SC 120 mg (Part 2) Arm 2: CT-P13 IV 3 mg/kg (Part 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/13 (61.54%)   7/11 (63.64%)   8/12 (66.67%)   9/12 (75.00%)   91/168 (54.17%)   90/175 (51.43%) 
Blood and lymphatic system disorders             
Neutropenia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  6/168 (3.57%)  4/175 (2.29%) 
Anaemia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  3/168 (1.79%)  3/175 (1.71%) 
Ear and labyrinth disorders             
Middle ear inflammation  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Gastrointestinal disorders             
Abdominal distension  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Abdominal pain  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  2/168 (1.19%)  1/175 (0.57%) 
Abdominal pain lower  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Abdominal pain upper  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  3/175 (1.71%) 
Diarrhoea  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  2/12 (16.67%)  4/168 (2.38%)  1/175 (0.57%) 
Flatulence  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  0/175 (0.00%) 
Gastritis  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  1/168 (0.60%)  0/175 (0.00%) 
Nausea  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  1/12 (8.33%)  4/168 (2.38%)  2/175 (1.14%) 
General disorders             
Localized injection site reaction  1 [1]  0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%)  2/12 (16.67%)  30/168 (17.86%)  22/175 (12.57%) 
Influenza like illness  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Pyrexia  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  2/12 (16.67%)  0/168 (0.00%)  2/175 (1.14%) 
Infections and infestations             
Bronchitis  1  0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%)  0/12 (0.00%)  7/168 (4.17%)  4/175 (2.29%) 
Latent tuberculosis  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  8/168 (4.76%)  10/175 (5.71%) 
Oral herpes  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  7/168 (4.17%)  4/175 (2.29%) 
Upper respiratory tract infection  1  2/13 (15.38%)  1/11 (9.09%)  1/12 (8.33%)  2/12 (16.67%)  9/168 (5.36%)  13/175 (7.43%) 
Urinary tract infection  1  0/13 (0.00%)  2/11 (18.18%)  1/12 (8.33%)  0/12 (0.00%)  9/168 (5.36%)  9/175 (5.14%) 
Viral upper respiratory tract infection  1  2/13 (15.38%)  0/11 (0.00%)  1/12 (8.33%)  3/12 (25.00%)  13/168 (7.74%)  16/175 (9.14%) 
Angular cheilitis  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Cystitis  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  3/175 (1.71%) 
Influenza  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  3/175 (1.71%) 
Otosalpingitis  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Pharyngitis  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  3/168 (1.79%)  2/175 (1.14%) 
Rhinitis  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  1/168 (0.60%)  2/175 (1.14%) 
Vaginal infection  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  2/168 (1.19%)  1/175 (0.57%) 
Wound infection  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Injury, poisoning and procedural complications             
Infusion related reaction  1 [2]  2/13 (15.38%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  2/168 (1.19%)  9/175 (5.14%) 
Limb injury  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Spinal fracture  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Thoracic vertebral fracture  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Systemic injection reaction  1 [3]  0/13 (0.00%)  1/11 (9.09%)  1/12 (8.33%)  0/12 (0.00%)  2/168 (1.19%)  3/175 (1.71%) 
Delayed hypersensitivity  1 [4]  0/13 (0.00%)  2/11 (18.18%)  2/12 (16.67%)  0/12 (0.00%)  5/168 (2.98%)  1/175 (0.57%) 
Investigations             
Alanine aminotransferase increased  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  8/168 (4.76%)  11/175 (6.29%) 
Aspartate aminotransferase increased  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  3/168 (1.79%)  7/175 (4.00%) 
Blood creatine phosphokinase increased  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  3/168 (1.79%)  2/175 (1.14%) 
Electrocardiogram abnormal  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Gamma-glutamyltransferase increased  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  3/168 (1.79%)  3/175 (1.71%) 
Glucose urine  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Transaminases increased  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  1/168 (0.60%)  3/175 (1.71%) 
Weight decreased  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Beta-2 glycoprotein antibody positive  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Musculoskeletal and connective tissue disorders             
Rheumatoid arthritis  1  4/13 (30.77%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  8/168 (4.76%)  8/175 (4.57%) 
Arthralgia  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  2/168 (1.19%)  1/175 (0.57%) 
Muscular weakness  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Musculoskeletal pain  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Nervous system disorders             
Headache  1  1/13 (7.69%)  1/11 (9.09%)  0/12 (0.00%)  1/12 (8.33%)  7/168 (4.17%)  11/175 (6.29%) 
Radiculopathy  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Reproductive system and breast disorders             
Cervical polyp  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Rhinitis allergic  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  0/175 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  0/168 (0.00%)  1/175 (0.57%) 
Dermatitis atopic  1  0/13 (0.00%)  0/11 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  0/168 (0.00%)  0/175 (0.00%) 
Erythema  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  2/168 (1.19%)  1/175 (0.57%) 
Night sweats  1  0/13 (0.00%)  0/11 (0.00%)  0/12 (0.00%)  1/12 (8.33%)  0/168 (0.00%)  1/175 (0.57%) 
Rash  1  1/13 (7.69%)  0/11 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/168 (0.60%)  2/175 (1.14%) 
Vascular disorders             
Hypertension  1  0/13 (0.00%)  1/11 (9.09%)  0/12 (0.00%)  0/12 (0.00%)  3/168 (1.79%)  4/175 (2.29%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
[1]
General disorders and administration site conditions; preferred term reported as injection site reaction
[2]
Infusion related reaction occurred between start of administration and 24 hours from the end of IV infusion (including placebo for Part 2)
[3]
Systemic injection reaction occurred between start of administration and 24 hours from the SC injection (including placebo for Part 2)
[4]
Delayed hypersensitivity occurred after 24 hours from the study drug administration
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: SungHyun Kim
Organization: Celltrion. Inc.
Phone: +82 32 850 5778
EMail: SungHyun.Kim@celltrion.com
Layout table for additonal information
Responsible Party: Celltrion
ClinicalTrials.gov Identifier: NCT03147248    
Other Study ID Numbers: CT-P13 3.5 (SC)
2016-002125-11 ( EudraCT Number )
First Submitted: May 7, 2017
First Posted: May 10, 2017
Results First Submitted: December 9, 2019
Results First Posted: April 8, 2020
Last Update Posted: April 8, 2020