| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Moderate to severe active rheumatoid arthritis (RA) diagnosed according to the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria (Aletaha
et al., 2010) for at least 24 weeks, who have inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). |
|
| E.1.1.1 | Medical condition in easily understood language |
| moderate to severe active rheumatoid arthritis (RA) |
|
| 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 | 23.1 |
| 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 |
|
| 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 evaluate usability of AI assessed by patient (POST-self-injection assessment questionnaire
[SIAQ]) at Week 2 |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate additional usability of AI up to Week 2
To evaluate efficacy, safety and immunogenicity up to Week 12 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each patient must meet all of the following criteria to be enrolled in this study:
1. Patient is male or female aged 18 to 70 years old, both inclusive.
2. Patient with a body weight of <100 kg.
3. Patient must be able and willing to self-administer SC injections.
4. 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).
5. Patient must have moderate to severe disease activity as defined by all of the following at Screening:
• 6 or more swollen joints (of 66 assessed)
• 6 or more tender joints (of 68 assessed)
• either an ESR ≥28 mm/hour or a serum C-reactive protein (CRP) concentration ≥1.0 mg/dL
(≥10 mg/L)
6. Patient who has been receiving oral or parenteral MTX for at least 12 weeks and who has been on a
stable dose and route of MTX between 10 to 25 mg/week for at least 8 weeks prior to the first administration of the study drug (Day 1).
7. 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 ≤2.0 × ULN
• Serum aspartate aminotransferase ≤2.0 × ULN
• Serum total bilirubin ≤1.5 × ULN
8. Patient has the following hematology laboratory test results at Screening:
• Absolute neutrophil count ≥2,000/mm3 (2.0×103/μL)
•Platelet count ≥100,000/mm3 (100.0×103/μL)
9. Patient and their partner of childbearing potential must agree to use following highly effective
method of contraception consistent with local regulations throughout the study and for 6 months
after the last dose of assigned treatment. 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
(i.e., a man is fertile after puberty unless permanently sterile by bilateral orchidectomy or a woman
is fertile, following menarche and until becoming postmenopausal unless permanently sterile).
-Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives
associated with inhibition of ovulation
- Intrauterine device or system
- True abstinence, when this is in line with the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods),
declaration of abstinence for the duration of exposure to investigational drug, and withdrawal are not acceptable methods of contraception.
- Double contraceptive methods (e.g., male condom in addition to use of hormonal or barrier method in female); for male patient with his female partner of childbearing potential only.
If patient or their partner has been surgically sterilized for less than 24 weeks prior to the date of
informed consent, they must agree to use any medically acceptable methods of contraception.
Postmenopausal females must have experienced their last menstrual period more than 1 year prior to
the date of informed consent without an alternative medical cause to be classified as not of
childbearing potential.
10. 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 with date prior to participation in the study. |
|
| E.4 | Principal exclusion criteria |
1. Patient who has previously received investigational or licensed product; targeted synthetic DMARD(s) for the treatment of RA and/or an interleukin-6 (IL-6) inhibitor for any purposes.
2. Patient who has previously received more than 1 biologic agents approved for the treatment of RA.
3. 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.
4. Patient who currently has, or has a history of, any of the following infections:
• A known infection with hepatitis B or 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 prior to the first administration of the study drug (Day 1), or a serious infection associated with hospitalization and/or which required parenteral injection of antibiotics within 24 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. However, a patient who has a past diagnosis with sufficient documentation of complete resolution of the infection can be enrolled in the study.
• Patient has active tuberculosis, latent TB (defined as a positive result for interferon-γ release assay [IGRA] with no active lesion in examination of chest X-ray without any sign or symptom of TB), a history of active TB , had close contact with a person with active TB or traveled to areas within a high incidence of TB within 8 weeks prior to study drug administration, or has plans to travel to an area with a high incidence of TB during the study period. If the result of IGRA is indeterminate at the screening, retest will be allowed only once during the screening period. If the repeated IGRA result is again indeterminate or positive, the patient will be excluded from the study. If the repeated IGRA result is negative, the patient can be included in the study.
5. Patient who has received or plans to receive any of the following prohibited medications or
treatment:
• Intra-articular corticosteroids within 4 weeks prior to the first administration of the study
drug (Day 1). A patient is permitted to receive either oral or parenteral glucocorticoids (≤10 mg daily of prednisone/prednisolone or equivalent) and non-steroidal antiinflammatory drug, if they have received a stable dose for at least 4 weeks prior to the first administration of the study drug (Day 1) and the same dose must be maintained during the study period. In addition, a patient is permitted to receive low-potency topical, inhaled,otic, and ophthalmic glucocorticoid preparations provided, if the preparations are
administered per the instructions on the product label.
• Conventional DMARDs, other than MTX, including hydroxychloroquine, chloroquine, or
sulfasalazine within 4 weeks prior to the first administration of the study drug (Day 1). A
patient who discontinued leflunomide and have had successful chelation with 8 g of
cholestyramine (3 times daily) for 11 days must wait 4 weeks after the last dose of
cholestyramine prior to the first administration of the study drug (Day 1). A patient who
discontinued leflunomide and did not have cholestyramine washout must wait 12 weeks
after the last dose of leflunomide prior to the first administration of the study drug (Day 1)
• Any other investigational device or medical product within 4 weeks prior to the first
administration of the study drug (Day 1) or 5 half-lives, whichever is longer
• Alkylating agents within 1 year prior to the first administration of the study drug (Day 1)
• Herbal treatment within 2 weeks prior to the first administration of the study drug (Day 1)
• Live or live-attenuated vaccine within 4 weeks prior to the first administration of the study
drug (Day 1), or any planned live or live-attenuated vaccination during the study period
• Any surgical procedure, including bone or joint surgery or synovectomy (including joint
fusion or replacement) within 12 weeks prior to the first administration of the study drug
(Day 1) or planned during the study period
6. Severe physical incapacitation.
7. Female patient who is currently pregnant or breastfeeding, or plans to become pregnant or
breastfeed within 6 months of the last dose of study drug. Male patient who is planning to donate
sperm or father a child within 6 months of the last dose of study drug.
8. Patient who currently abuses alcohol or drugs or has a history of alcohol or drug abuse within
1 years from Screening.
9. Patient is vulnerable.
10. Patient who, in the opinion of the investigator, should not participate in the study.
Please refer to the protocol to see the whole list of exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The usability of AI as assessed by patients rating using POST-Self-Injection Assessment Questionnaire (SIAQ) at Week 2. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• The usability of AI as assessed by patients rating using PRE- and POST-SIAQ
• The usability of AI as assessed by patients rating using PRE-SIAQ
• The observer rating of successful self-injection of AI using self-injection assessment checklist
• Change from baseline in disease activity score (DAS) 28 (C-reactive protein [CRP] and
erythrocyte sedimentation rate [ESR]) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• The usability of AI as assessed by patients rating using PRE- and POST-SIAQ at Week 0.
• The usability of AI as assessed by patients rating using PRE-SIAQ at Week 2.
• The observer rating of successful self-injection of AI using self-injection assessment checklist at
Weeks 0 and 2.
• Change from baseline in disease activity score (DAS) 28 (C-reactive protein [CRP] and
erythrocyte sedimentation rate [ESR]) up to Week 12. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Usability of Subcutaneous Auto-injector of CT-P47 in Patients with Moderate to Severe Active Rheumatoid Arthritis |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
The end of trial is defined as the date that the final database lock with
no further database change for the final CSR. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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