Active Rheumatoid Arthritis MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Code: CT-P13
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Sponsors
Celltrion, Inc
Eligibility
Sex/Gender
All
Inclusion 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 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
Exclusion criteria
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 ei
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) ; 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) ; 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 ; 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. Primary pharmacokinetic assessment will be done at steady state between Week 22 and 30 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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: Secondary Endpoints for Part 1 The following secondary PK endpoints will be assessed between Week 22 and Week 30: •AUCss8W -Total exposure over the 8 weeks interval from Week 22 to Week 30 •Cmax-Observed maximum serum concentration after study drug administration •Tmax-Time of observed maximum serum concentration •T1/2-Terminal half life •Ctrough-Trough concentration (concentration before the next study drug administration) •MRT-Mean residence time •CL-Clearance after IV dosing •CL/F-Apparent clearance after SC dosing •BA-Bioavailability (absolute and/or relative) •AUCt/DN-Dose normalized total exposure over dosing interval (=AUCt/total dose administered) •Cmax/DN-Dose normalized peak exposure (=Cmax/total dose administered) The following secondary PK endpoint will be assessed up to Week 54: •Ctrough-Trough concentration (concentration before the next study drug administration) | — |
Countries
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
Public ContactSung Young Lee
Celltrion, Inc
Outcome results
None listed