E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Active Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
To demonstrate that CT-P17 is equivalent to Humira, in terms of efficacy as determined by clinical response according to the ACR definition of a 20% improvement (ACR20) at Week 24. |
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E.2.2 | Secondary objectives of the trial |
To evaluate additional efficacy, PK, pharmacodynamics (PD), and overall safety, including immunogenicity and biomarker. |
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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, both inclusive.
2. Patient has had a diagnosis of RA according to the 2010 ACR/EULAR classification criteria (Aletaha et al., 2010) for at least 24 weeks prior to the first administration of the study drug (Day 1).
3. Patient who has active disease as defined by the presence of 6 or more swollen joints (of 66 assessed), 6 or more tender joints (of 68 assessed) and either an erythrocyte sedimentation rate (ESR) >28 mm/hour or a serum C-reactive protein (CRP) concentration >1.0 mg/dL (>10 mg/L) at Screening.
4. Patient who has been receiving oral or parenteral MTX at a dose of between 12.5 to 25 mg/week, or 10 mg/week if intolerant to a higher dose, and who has been on a stable dose and route of MTX for at least 4 weeks prior to the first administration of the study drug (Day 1).
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) (SI [Système International d'Unités] units: 0.84 mL/s)
• Serum alanine aminotransferase ≤3.0 × ULN
• Serum aspartate aminotransferase ≤3.0 × ULN
• Serum total bilirubin ≤1.5 × ULN
6. Patient has the following hematology laboratory test results at Screening:
• Hemoglobin >8.0 g/dL (SI units: >80 g/L or 4.96 mmol/L)
• Absolute neutrophil count ≥1.5 × 10Exp3 cells/μL (SI units: ≥1.5 × 10Exp9 cells/L)
• Platelet count ≥75 × 10Exp3 cells/μL (SI units: ≥ 75 × 10Exp9 cells/L)
7. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of the study, including possible risks and side effects, has the ability to cooperate with the investigator and is given ample time and opportunity to read and understand verbal and/or written instructions, and signs the written informed consent form (ICF) with date prior to participation in the study.
8. Patient and their partner of childbearing potential must agree to use a highly effective method of contraception throughout the study and for 6 months after the last dose of assigned treatment. Examples include the following:
• Hormonal contraceptives (combined or progestogen-only) associated with inhibition of ovulation.
• Intrauterine devices.
• Sexual abstinence (not periodically, but for the entire period of risk).
A man or woman is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. Male and female patients and their partners who have been surgically sterilized for less than 24 weeks 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 1 year prior to the date of informed consent to be classified as not of childbearing potential.
9. Patient must be able and willing to self-administer SC injections or designate a qualified person(s) to administer SC injection. |
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E.4 | Principal exclusion criteria |
1. Patient who has previously received investigational or licensed product; biologic or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) (e.g., tofacitinib, baricitinib) for the treatment of RA and/or tumor necrosis factor (TNF) α inhibitor for any purposes.
2. Patient who has allergies to any of the excipients of study drug or any other murine and human proteins, or patient with a hypersensitivity to immunoglobulin products.
3. Patient who currently has, or has a history of, any of the following infections: - A known infection with hepatitis B (active or carrier of hepatitis B), hepatitis C, or infection with human immunodeficiency virus (HIV). However, a patient with past hepatitis B virus is allowed if resolved. -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 1). - Recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug (Day 1). - Past or current granulomatous infections or other severe or chronic infections (such as sepsis, abscess, opportunistic infections, or invasive fungal infections such as histoplasmosis). A patient who has a past diagnosis with sufficient documentation of complete resolution of the infection can be enrolled in the study. - Other serious infections within 24 weeks prior to the first administration of the study drug (Day 1).
4. Patient who currently has, or has a history of, any of the following TB conditions: - Patient who has a history of TB or a current diagnosis of TB. A patient who has a previous diagnosis of active TB cannot be enrolled in the study even if there is sufficient documentation of complete resolution of active TB.Patient who has had exposure to a person with active TB such as first-degree family members or co-workers. - Patient who has an indeterminate result for interferon-γ release assay (IGRA) or latent TB (defined as a positive result of IGRA with a negative examination of chest X-ray) at Screening. A patient who has a previous diagnosis of latent TB cannot be enrolled despite sufficient documentation of prophylaxis. If the result of the IGRA is indeterminate at Screening, 1 retest will be possible during the Screening period. If the repeated IGRA result is indeterminate again or positive, the patient will be excluded from the study. If the repeated IGRA result is negative, the patient can be enrolled in the study.
Refer to Protocol for the complete list of Exclusion Criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving clinical response (according to the ACR20 criteria) at Week 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints:
- ACR20 (except for Week 24), ACR50 and ACR70
- Individual components of the ACR
- Hybrid ACR response
- DAS28 (CRP) and DAS28 (ESR)
- Individual components of the DAS28
- EULAR response
- Simplified disease activity index (SDAI) and clinical disease activity index (CDAI)
- SF-36 version 2
-Joint damage progression based on radiographic evaluations
Pharmacokinetic Assessment:
- Ctrough Trough concentration (concentration prior to the next study drug administration)
Pharmacodynamic Assessment:
Secondary Endpoints
The following PD endpoints will be assessed up to Week 48:
-CRP
-ESR
- Rheumatoid factor (RF)
- Anti-cyclic citrullinated peptide (anti-CCP) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints will be assessed up to Week 48.
Pharmacokinetic Assessment. endpoint will be assessed up to Week 52.
Pharmacodynamic Assessment. endpoints will be assessed up to Week 48:
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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 | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 |
Bulgaria |
Hungary |
Lithuania |
Peru |
Poland |
Ukraine |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |