A Phase I Study to Evaluate Pharmacokinetics, Efficacy and Safety of CT-P13 Subcutaneous in Patients With Active Crohn's Disease and Ulcerative Colitis

Study Overview
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Brief Summary
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Phase 1 randomized, open-label, multicenter, parallel-group study designed to evaluate efficacy, pharmacokinetics and safety between CT-P13 subcutaneous (SC) and CT-P13 intravenous (IV) in patients with active Crohn's Disease (CD) and active Ulcerative Colitis (UC).

Detailed Description
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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 1 randomized, open-label, multicenter, parallel-group study is designed to evaluate efficacy, pharmacokinetics and safety between CT-P13 SC and CT-P13 IV in patients with active CD and active UC.

Official Title
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An Open-label, Randomized, Parallel-Group, Phase I Study to Evaluate Pharmacokinetics, Efficacy and Safety Between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients With Active Crohn's Disease and Active Ulcerative Colitis

Conditions
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Crohn's Disease, Ulcerative Colitis (Part 2 Only)

Intervention / Treatment
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* Biological: CT-P13
* Biological: CT-P13
* Biological: CT-P13
* Biological: CT-P13
* Biological: CT-P13
* Biological: CT-P13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has active Crohn's disease with a score on the Crohn's disease activity index between 220 and 450 points. Patient has active Ulcerative colitis as defined by a total Mayo score between 6 and 12 points (Part 2 only). Exclusion Criteria: Patient who has previously received a biological agent for the treatment of CD and UC and/or a tumor necrosis factor-alpha (TNFα) inhibitor for the treatment of other disease Patient who has allergies to any of the excipients of infliximab or any other murine and/or human proteins or patient with a hypersensitivity to immunoglobulin product Patient who has a current or past history of infection with HIV, hepatitis B, or hepatitis C (carriers of hepatitis B and hepatitis C are not permitted to enrol into the study, but past hepatitis B resolved can be enrolled) Patient who has acute infection requiring oral antibiotics within 2 weeks or parenteral injection of antibiotics within 4 weeks prior to the first administration of the study drug, other serious infection within 6 months prior to the first administration of study drug or recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug Patient who has an indeterminate result for interferon-γ release assay (IGRA) or latent tuberculosis (TB) at Screening. For Part 2, if IGRA result is indeterminate at Screening, 1 retest will be possible during the screening. If the repeated IGRA result is negative, the patient can be included in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1: CT-P13 IV 5 mg/kg<br>CT-P13 IV (Infliximab), 5 mg/kg by IV infusion every 8 weeks (Part 1) | Biological: CT-P13<br>* CT-P13 (5 mg/kg) by IV infusion administered as a 2-hour IV infusion per dose every 8 weeks (Part 1)<br>* Other names: Infliximab;|
| Experimental: Cohort 2: CT-P13 SC 120 mg<br>CT-P13 SC (Infliximab), 120 mg by SC injection every 2 weeks (Part 1) | Biological: CT-P13<br>* CT-P13 (120 mg) by single SC injection every 2 weeks (Part 1)<br>* Other names: Infliximab;|
| Experimental: Cohort 3: CT-P13 SC 180 mg<br>CT-P13 SC (Infliximab), 180 mg by SC injection every 2 weeks (Part 1) | Biological: CT-P13<br>* CT-P13 (180 mg) by double SC 90 mg injections every 2 weeks (Part 1)<br>* Other names: Infliximab;|
| Experimental: Cohort 4: CT-P13 SC 240 mg<br>CT-P13 SC (Infliximab), 240 mg by SC injection every 2 weeks (Part 1) | Biological: CT-P13<br>* CT-P13 (240 mg) by double SC 120 mg injections every 2 weeks (Part 1)<br>* Other names: Infliximab;|
| Experimental: Arm 1: CT-P13 SC 120/240 mg<br>CT-P13 SC (Infliximab), either 120 mg or 240 mg every 2 weeks by SC injection (Part 2) | Biological: CT-P13<br>* CT-P13 (120 mg) by single SC injection every 2 weeks in patients with body weight less than 80 kg, and CT-P13 (240 mg) by double SC 120 mg injections in patients with body weight at or above 80 kg based on body weight at Week 6 (Part 2)<br>* Other names: Infliximab;|
| Active Comparator: Arm 2: CT-P13 IV 5 mg/kg<br>CT-P13 IV (Infliximab), 5 mg/kg by IV infusion every 8 weeks up to Week 22. CT-P13 IV was switched to either 120 mg or 240 mg of CT-P13 SC (Infliximab) treatment, and further doses with CT-P13 SC were given up to Week 54. (Part 2) | Biological: CT-P13<br>* CT-P13 (5 mg/kg) by IV infusion administered as a 2-hour IV infusion per dose every 8 weeks up to Week 22. From Week 30, CT-P13 (120 mg) by single SC injection every 2 weeks in patients with body weight less than 80 kg, and CT-P13 (240 mg) by double SC 120 mg injections in patients with body weight at or above 80 kg based on body weight at Week 30 (Part 2)<br>* Other names: Infliximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive Statistics of Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1) | For Part 1, the primary PK endpoint of the AUCτ 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 of Group A or B for PK monitoring visit period (Week 22 to Week 30). Therefore, AUCτ was calculated at Week 22 for Cohort 1: CT-P13 IV 5 mg/kg, Weeks 22 and 26 for Group A of SC cohorts, and Week 24 and 28 for Group B of SC cohorts. | Week 22, 24, 26 and 28 | 
| Analysis of Covariance Model (ANCOVA) of Observed Ctrough,week22 (Pre-dose Level at Week 22) (Part 2) | For Part 2, the primary endpoint was to demonstrate that CT-P13 SC is non-inferior to CT-P13 IV, in terms of pharmacokinetics, as determined by the observed Ctrough,week22 (pre-dose level at Week 22). | Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive Statistics for Actual Value of Crohn's Disease Activity Index (CDAI) Score (Part 2 - CD) | For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics for actual value of CDAI score up to Week 54 between the CT-P13 SC and CT-P13 IV treatment groups in active CD patients. The total CDAI scores range from 0 to over 600 with higher scores indicating increased severity of disease. The index is the sum of 8 components multiplied by the relevant weight factor; number of liquid or very soft stools (x2), abdominal pain (x5), general well-being (x7), CD complications (x20), taking lomotil/opiates for diarrhea (x30), abdominal mass (x10), deviation of hematocrit (x6), and percentage deviation from standard weight (x1). Efficacy assessments were done prior to each study drug administrations. Results up to Week 6 in both arms represent efficacy resulting from CT-P13 IV (5 mg/kg) loading dose treatment. | up to Week 54 | 
| Proportion of Patients Achieving Clinical Response According to CDAI-100 Criteria (Part 2 - CD) | For evaluation of efficacy, the secondary endpoint was defined as proportion of patients achieving clinical response according to CDAI-100 criteria up to Week 54 between the CT-P13 SC and CT-P13 IV treatment groups in active CD patients. Efficacy assessments were done prior to each study drug administrations. Results up to Week 6 in both arms represent efficacy resulting from CT-P13 IV (5 mg/kg) loading dose treatment. Responder according to CDAI-100 criteria was defined as a decrease in CDAI score of 100 points or more from the baseline value. | up to Week 54 | 
| Descriptive Statistics for Actual Value of Partial Mayo Score (Part 2 - UC) | For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics for actual value of partial Mayo score up to Week 54 between the CT-P13 SC and CT-P13 IV treatment groups in active UC patients. The partial Mayo scores range from 0-9 with higher scores indicating increased severity of disease. The index is sum of the 3 subscores, each which range from 0 to 3; stool frequency, rectal bleeding and physician's global assessment. Efficacy assessments were done prior to each study drug administrations. Results up to Week 6 in both arms represent efficacy resulting from CT-P13 IV (5 mg/kg) loading dose treatment. | up to Week 54 | 
| Proportion of Patients Achieving Clinical Response According to the Partial Mayo Score (Part 2 - UC) | For evaluation of efficacy, the secondary endpoint was defined as proportion of patients achieving clinical response according to the partial Mayo score up to Week 54 between the CT-P13 SC and CT-P13 IV treatment groups in active UC patients. Efficacy assessments were done prior to each study drug administrations. Results up to Week 6 in both arms represent efficacy resulting from CT-P13 IV (5 mg/kg) loading dose treatment. Responder according to partial Mayo score was defined as a decrease from baseline in partial Mayo score of at least 2 points, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1. | up to Week 54 | 
| Descriptive Statistics of Observed Ctrough (Trough Concentration [Before the Next Study Drug Administration]) of Infliximab (Part 2) | For evaluation of pharmacokinetics (PK), the secondary endpoint was defined as the analysis of trough concentration 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 enrolled patient received CT-P13 IV infusions at Weeks 0 and 2. Patients in SC group were administered with CT-P13 SC at Week 6 and every 2 weeks thereafter up to Week 54. Patients in IV group were administered with CT-P13 IV at Week 6 and every 8 weeks thereafter up to Week 22. Then, CT-P13 IV was switched to CT-P13 SC at Week 30, and further doses with CT-P13 SC were given up to Week 54. 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. All patients in PK population were analyzed according to the treatment they received. | up to Week 54 | 
| Descriptive Statistics for Actual Value in Fecal Calprotectin Concentration (Pharmacodynamic Parameter) (Part 2) | For evaluation of pharmacodynamic (PD), the secondary endpoint was defined as concentration of Fecal Calprotectin (FC) between 2 treatment groups up to Week 54. The fecal samples for FC were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. All enrolled patients received CT-P13 IV infusions at Weeks 0 and 2. Then, patients in CT-P13 SC group were administered with CT-P13 SC at Week 6 and every 2 weeks thereafter up to Week 54. Patients in the CT-P13 IV group were administered with CT-P13 IV at Week 6 and every 8 weeks thereafter up to Week 22 (Weeks 14 and 22). And then, CT-P13 IV was switched to CT-P13 SC based on body weight at Week 30, and further doses with CT-P13 SC were given up to Week 54. All patients in the PD population were analyzed according to the treatment they received. | up to Week 54 |