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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 25 November 2019
Main ID:  EUCTR2016-002125-11-HU
Date of registration: 11/07/2016
Prospective Registration: Yes
Primary sponsor: Celltrion, Inc
Public title: Evaluating efficacy, pharmacokinetics and safety between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients with Active Rheumatoid Arthritis
Scientific title: A Randomized, Parallel-Group, Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients with Active Rheumatoid Arthritis
Date of first enrolment: 08/09/2016
Target sample size: 258
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002125-11
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: yes
Other trial design description: Part 1 is open; placebo double blind, double dummy design is introduced in Part 2 only
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: yes
Other: no
Number of treatment arms in the trial: 4
 
Phase:  Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Bosnia and Herzegovina Bulgaria Chile Czech Republic Estonia Hungary Italy
Korea, Republic of Latvia Lithuania Mexico Peru Poland Russian Federation Slovakia
South Africa Spain Ukraine
Contacts
Name: Sung Young Lee   
Address:  23, Academy-ro 22014 Yeonsu-gu, Incheon Korea, Republic of
Telephone: +82328506532
Email: SungYoung.Lee@celltrion.com
Affiliation:  Celltrion, Inc
Name: Sung Young Lee   
Address:  23, Academy-ro 22014 Yeonsu-gu, Incheon Korea, Republic of
Telephone: +82328506532
Email: SungYoung.Lee@celltrion.com
Affiliation:  Celltrion, Inc
Key inclusion & exclusion criteria
Inclusion criteria:
1. Patient is male or female aged 18 to 75 years old, inclusive.
2. Patient has a diagnosis of RA according to the 2010 ACR/EULAR classification criteria [Aletaha et al. 2010] for at least 6 months prior to the first administration of the study drug (Day 0).
3. Patient has active disease as defined by the presence of 6 or more swollen joints (of 28 assessed), 6 or more tender joints (of 28 assessed), and a serum CRP concentration > 0.6 mg/dL at Screening. Unexplained or unexpected Screening CRP value that does not match the clinical activity of RA according to the investigator’s assessment or recent test can be retested once within the Screening period.
4. Patient who has completed at least 3 months of treatment of oral or parenteral dosing with methotrexate between 12.5 to 25 mg/week and on stable dosing with methotrexate between 12.5 to 25 mg/week for at least 4 weeks prior to the first administration of the study drug (Day 0).
5. Patient has adequate renal and hepatic function at Screening as defined by the following clinical chemistry results:
• Serum creatinine <1.5 × upper limit of normal (ULN) or an estimated creatinine clearance level >50 mL/min (by Cockcroft-Gault formula)
• Serum alanine aminotransferase <2.5 × ULN
• Serum aspartate aminotransferase <2.5 × ULN
• Serum total bilirubin <2 × ULN
6. Patient has the following hematology laboratory test results at Screening:
• Hemoglobin =8.5 g/dL (SI [Système International d'Unités] units: =85 g/L or 5.28 mmol/L)
• White blood cell count =3.5 × 103 cells/µL (SI units: =3.5 × 109 cells/L)
• Neutrophil count =1.5 × 103 cells/µL (SI units: =1.5 × 109 cells/L)
• Platelet count =100 × 103 cells/µL (SI units: =100 × 109 cells/L)
7. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study.
8. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read or understand this information, signed and dated the written informed consent before inclusion in the study.
9. For both male and female patients, the patient and their partners of childbearing potential agree to use one of the following medically acceptable methods of contraception during the course of the study and for 6 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilized):
• Barrier contraceptives (male condom, female condom, or diaphragm with a spermicidal gel)
• Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings)
• Intrauterine device
Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use any medically acceptable methods of contraception.
Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not of childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 208
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1.Patient who has previously received a biological agent for the treatment of RA
2.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.
3.Patient who has a current or past history of following infection:
•Current or past history of chronic infection with hepatitis C or HIV-1 or-2 or current infection with hepatitis B
•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 (Day 0)
•Other serious infection within 6 months prior to the first administration of the study drug (Day 0)
•Recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug (Day 0)
•Past or current granulomatous infections or other severe or chronic infection
4.Patient who has a medical condition including one or more of the following:
•Classified as obese (body mass index =35 kg/m2)
•Uncontrolled diabetes mellitus, even after insulin treatment
•Uncontrolled hypertension (as defined by systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg)
•Any other inflammatory or rheumatic diseases
•History of any malignancy within the 5 years prior to the first administration of the study drug (Day 0)except completely excised and cured squamous carcinoma of the uterine cervix in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma
•History of lymphoma or lymphoproliferative disease or bone marrow hyperplasia
•NYHA class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina or clinically significant electrocardiogram [ECG] abnormalities), or myocardial infarction within the 6 months prior to the first administration of the study drug (Day 0)
•History of organ transplantation, including corneal graft/transplantation
•Any uncontrolled, clinically significant respiratory disease, including but not limited to chronic obstructive pulmonary disease, asthma, bronchiectasis, or pleural effusion.
•Previous diagnosis or symptoms suggestive of demyelinating disorders, including multiple sclerosis and Guillain-Barré syndrome
•Severe physical incapacitation (unable to perform routine self-care, has RA ACR functional status class 4 or who cannot benefit from medication
•Any conditions significantly affecting the nervous system if it may interfere with the investigator’s assessment on disease activity scores including joint counts
•Any other serious acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results.
5.Patient who has received or has plan to receive any of following prohibited medications or treatment:
•Any biological agents for the treatment of RA
•Intra-articular corticosteroids within 4 weeks prior to the first administration of the study drug (Day 0). Patient is permitted to receive either oral or parenteral glucocorticoids (=10 mg daily of prednisone/prednisolone or equivalent), and nonsteroidal anti-inflammatory drug, if they have received a stable dose for at least 4 weeks prior to the first administration of the study drug (Day 0). In addition, patients are permitted to receive low potency topical, otic, and ophthalmic glucocorticoid preparations provided the preparat


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Active Rheumatoid Arthritis
MedDRA version: 19.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Intervention(s)

Product Code: CT-P13
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: CT-P13
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: CT-P13
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: CT-P13
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: REMSIMA
Product Code: CT-P13
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: CT-P13
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)
Main Objective: Part 1
• To find the optimal dose of CT-P13 SC over the first 30 weeks as determined by the area under the concentration-time curve (AUCt) at steady state between Week 22 and Week 30
Part 2
• To demonstrate that CT P13 SC is noninferior to CT-P13 IV at Week 22, in terms of efficacy, as determined by clinical response according to change from baseline in disease activity measured by Disease Activity Score using 28 joint counts (DAS28) (CRP)
Primary end point(s): Efficacy Assessments: Primary Endpoint for Part 2
• Change from baseline in disease activity measured by DAS28 (CRP) at Week 22

Pharmacokinetic Assessments: Primary Endpoint for Part 1
The following primary PK endpoint will be assessed at steady state between Week 22 and 30:
• AUCt Area under the concentration-time curve at steady state between Week 22 and Week 30
Secondary Objective: Part 1
• To evaluate efficacy, pharmacokinetics (PK), pharmacodynamics (PD) and overall safety of CT P13 SC in comparison with CT-P13 IV up to Week 54
Part 2
• To evaluate efficacy, PK, PD and overall safety of CT-P13 SC in comparison with CT-P13 IV (over the first 30 weeks)
• To evaluate efficacy, PK, PD and overall safety of CT-P13 SC up to Week 54
Tertiary Objective for Part 2
• To evaluate biomarkers (optional)
Timepoint(s) of evaluation of this end point: Primary efficacy will be assessed by change from baseline in disease activity measured by DAS28 (CRP) at Week 22.
Secondary Outcome(s)
Secondary end point(s): Efficacy Assessments: Secondary Endpoints for both Part 1 and Part 2
The following secondary efficacy endpoints will be assessed:
• Individual components of the DAS28
• DAS28 (CRP) and DAS28 (ESR)
• Individual components of the ACR
• ACR 20, 50 and 70
• Hybrid ACR response
• Proportion of patients with a good response, defined according to the EULAR response criteria
• SDAI and CDAI
• Health assessment questionnaire (HAQ)
36-item short form health survey (SF-36) (Part 2 only)

Pharmacokinetic Assessments: Secondary Endpoints for Part 1
The following secondary PK endpoints will be assessed between Week 22 and Week 30:
• Cmax Observed maximum serum concentration
• MRT Mean residence time
• CL Clearance after IV dosing
• CL/F Apparent clearance after SC dosing
• BA Bioavailability (absolute and/or relative)

The following secondary PK endpoint will be assessed up to Week 54:
• Ctrough Trough concentration

Secondary Endpoints for Part 2
The following secondary PK endpoints will be assessed between Week 22 and Week 30:
• AUCt Area under the concentration-time curve at steady state between Week 22 and Week 30
• Cmax Observed maximum serum concentration

The following secondary PK endpoint will be assessed up to Week 54:
Ctrough Trough concentration

Pharmacodynamic Assessments:
Secondary Endpoints for both Part 1 and Part 2
The following PD parameters for CT-P13 SC and CT-P13 IV will be determined as secondary PD endpoints (up to Week 54):
• Rheumatoid Factor (RF)
• Anti-cyclic citrullinated peptide (anti-CCP)
• CRP
• ESR

Biomarker Assessment (Optional for Part 2): For patients who sign a separate informed consent form for the biomarker assessment, a blood sample for evaluation of any necessary genotypes will be collected before dosing on Day 0 of Week 0. These genes will include, but are not limited to Fc?RIIIa.

Safety assessments will be performed on immunogenicity, hypersensitivity monitoring (including delayed hypersensitivity monitoring), vital sign measurements (including blood pressure, heart and respiratory rates and body temperature), weight, interferon-? release assay, chest x-ray, hepatitis B and C and HIV-1 and -2 status, physical examination findings, ECGs, AEs (including serious AEs), adverse events of special interest (infusion related reactions/hypersensitivity/anaphylactic reactions, delayed hypersensitivity, injection site reactions, infection and malignancies), clinical laboratory analyses, pregnancy testing, local site pain using 100 mm Visual Analogue Scale (VAS), signs and symptoms of TB and previous and concomitant medications.
In case of delayed hypersensitivity occurred after 24 hours of study drug administration, including serum sickness-like reactions (myalgia with fever or rash, arthralgia, lymphadenopathy, skin eruption or edema), following assessments will be additionally performed to determine Serum Sickness during the study period;
• Immunogenicity
• Clinical Laboratory Analyses
• Complement (C3, C4) and Total Haemolytic Complement
Timepoint(s) of evaluation of this end point: Secondary efficacy will be assessed at the time points specified in the schedule of events
The secondary PK endpoint evaluations will be conducted during the Treatment Period up to Week 54, with blood samples for analysis obtained at the time points specified in the schedule of events.
Efficacy, pharmacodynamics, safety and biomarkers assessments will be performed at the time points specified in the schedule of events.
Secondary ID(s)
2016-002125-11-LV
CT-P13-3.5
Source(s) of Monetary Support
Celltrion, Inc
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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