E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate that CT P13 is equivalent to Remicade up to Week 30, in terms of efficacy as determined by clinical response according to the American College of Rheumatology (ACR) definition of a 20% improvement (ACR20). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate long term efficacy, pharmacokinetics, pharmacodynamics, and overall safety of CT P13 in comparison with Remicade reference product up to Week 54. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is male or female aged 18 to 75 years old, inclusive. 2. Patient was diagnosed with active RA according to the revised 1987 ACR classification criteria [Arnett et al 1987] for at least 1 year prior to Screening. 3. Patients have active disease as defined by the presence of 6 or more swollen joints, and 6 or more tender joints, and at least two of the following: morning stiffness lasting at least 45 minutes, an erythrocyte sedimentation rate greater than 28 mm/h, and a serum C reactive protein (CRP) concentration greater than 2.0 mg/dL (Maini et al 1999). 4. Patients who have 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 Screening. 5. Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (eg, barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings), and intrauterine devices) during the course of the study and for 6 months following discontinuation of study treatments (excluding women who are not of childbearing potential and men who have been sterilized). 6. Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to study entry must agree to use 2 medically accepted methods of contraception as per inclusion criterion 5. 7. Menopausal females must have experienced their last period more than 12 months prior to study entry to be classified as not of childbearing potential. 8. Patients have adequate renal and hepatic function at Screening as defined by the following clinical chemistry results: • Serum creatinine <1.7 × upper limit of normal (ULN) or an estimated creatinine clearance level >75 mL/min • Serum alanine aminotransferase <2 × ULN • Serum aspartate aminotransferase <2 × ULN 9. Patients are permitted to receive both oral glucocorticoids equivalent to ≤10 mg daily prednisolone and nonsteroidal anti-inflammatory drugs, if they have received a stable dose for at least 4 weeks prior to Screening. 10. Patients have 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 written instructions, and to comply with the requirements of the entire study. 11. 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 and understand this information, signed and dated the written informed consent before inclusion in the study.
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E.4 | Principal exclusion criteria |
1. Patients who have previously been administered a biological agent for the treatment of RA. 2. Patients who have allergies to any of the excipients of infliximab or any other murine and human proteins. 3. Patients who have a current or past history of chronic infection with hepatitis B, hepatitis C, or infection with human immunodeficiency virus -1 or-2 or who have a positive result to the screening test for those infections. 4. Patients who have a current diagnosis of TB or other severe or chronic infection (such as sepsis, abscess or opportunistic infections, or invasive fungal infection such as histoplasmosis) or a past diagnosis without sufficient documentation of complete resolution following treatment. 5. Patients who have had recent exposure to persons with active TB, or who have a positive result to the screening test for latent TB defined as a positive result of interferon-γ release assay with a negative examination of chest x-ray, and who have not received at least the first 30 days of country-specific TB therapy and do not intend to complete the entire course of that therapy. 6. Patients who have had any other serious infection not already excluded in the 6 months before Screening or have a history of chronic infection. 7. Patients who have a current or past history of drug or alcohol abuse. 8. Patients who have a medical history including one or more of the following conditions: • Bone marrow hypoplasia • Diabetes mellitus unless on a stable dosing regimen for at least 4 weeks prior to Screening • Any other inflammatory rheumatic disease and other chronic painful musculoskeletal or neuropathic conditions such as fibromyalgia • Any malignancy within the previous 5 years except completely excised and cured squamous carcinoma of the uterine cervix, cutaneous basal cell carcinoma, or squamous cell carcinoma • Congestive heart failure (New York Heart Association [NYHA] Class III/IV) or unstable angina • Organ transplantation • Severe physical incapacitation • Moderate, severe or very severe chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria • Previous diagnosis or symptoms suggestive of demyelinating disorders, including multiple sclerosis and Guillain-Barre syndrome • Any condition significantly affecting the nervous system (ie, nervous system damage) if it may interfere with the investigator’s assessment on disease activity scores including joint counts 9. Patients taking any of the following concomitant medications: • Corticosteroids, except oral glucocorticoids of maximum equivalent daily dose of 10 mg of prednisolone within 4 weeks prior to Screening • Disease-modifying antirheumatic drugs (DMARDs), other than methotrexate, within 4 weeks prior to Screening. Patients who discontinued leflunomide and have had successful chelation with 8 g of cholestyramine (3 times daily) for 11 days must wait 4 weeks prior to Screening. Patients who discontinued leflunomide and did not have cholestyramine washout must wait 12 weeks after last dose of leflunomide before Screening • Alkylating agents within 12 months prior to Screening 10. Patients who have participated in a study with an investigational drug within 6 months of Screening or who are currently receiving treatment with any other investigational drug or device. 11. Female patients who are currently pregnant or breastfeeding, or are planning to become pregnant or breastfeed within 6 months of the last dose of CT P13 or Remicade reference product. 12. Patients who have received a live or live attenuated vaccination within 8 weeks of Screening or who are scheduled to receive a live or live attenuated vaccination. Killed vaccines are acceptable during the study. 13. Patients who, in the opinion of their general practitioner or investigator, should not participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of patients achieving clinical response according to the ACR20 criteria at Week 30. A patient is defined as a responder according to ACR20 criteria if the following are fulfilled: •A decrease of at least 20% in the number of tender joints •A decrease of at least 20% in the number of swollen joints and •A 20% improvement in three of the following: •Patient’s assessment of pain on the VAS •Patient and physician global assessment of disease status (VAS) •Health assessment questionnaire estimate of physical ability •Serum CRP concentration •ESR
The VAS range is from 0 to 100 mm, with higher scores indicating poorer status or more severe pain.
For the derivation of ACR20 at Week 30 the following categories of patients are considered nonresponders: •Patients with an improvement according to the ACR criteria of less than 20% •Patients who discontinue the study prior to Week 30 except for safety reasons •Patients with missing or incomplete data for the evaluation of ACR20 at Week 30 •Patients with protocol prohibited changes in medication including initiation therapy with a new DMARD, increase in dose of RA medication (methotrexate or corticosteroid) and administration of intra articular corticosteroids in more than 1 joint •Patients requiring a surgical joint procedure during the study
This approach should also be used for other time points where ACR20 is derived.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 91 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |