| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Chronic Plaque Psoriasis |
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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] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
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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 the pharmacokinetics (PK) similarity between patients receiving Humira continuously and those who alternate between Humira and CT-P17 in terms of area under the concentration-time curve over the dosing interval of Week 25-27 (AUCtau, 25-27) and maximum serum concentration during the dosing interval of Week 25-27 (Cmax, 25-27) |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate additional PK, efficacy and overall safety including immunogenicity |
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| 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 75 years old, both inclusive.
2. Patient has had a diagnosis of chronic plaque psoriasis for at least 24 weeks prior to the first administration of the study drug (Day 1).
3. Patient has stable moderate to severe plaque psoriasis with or without psoriatic arthritis at both Screening and at the time of the first administration of the study drug (Day 1) as defined by:
• Psoriasis Area and Severity Index (PASI) score of 12 or greater and
• Static Physician’s Global Assessment (sPGA) score of 3 or greater and
• Body Surface Area (BSA) affected by plaque psoriasis of 10% or greater.
4. Patient who is a candidate for systemic therapy or phototherapy.
5. Patient (or legal guardian, if applicable) is informed of the full nature and purpose of the study, including possible risks and side effects, is able 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.
6. Female patient who is considered of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) must agree to use highly effective methods of contraception consistent with local regulations during the course of the study and at least 20 weeks following discontinuation of study drug (excluding women who are not of childbearing potential). Examples include the following:
a) Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives associated with inhibition of ovulation
b) Intrauterine device or intrauterine hormone-releasing system
c) 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.
Male patient who is sexually active with a woman of childbearing potential must agree to use the highly effective method described as above or medically acceptable methods of contraception (e.g., male or female condom AND additional hormonal or barrier method by female partner) consistent with local regulations during the study and for 20 weeks following discontinuation of study drug. If patient or their partner has been surgically sterilized for less than 24 weeks prior to the date of informed consent form (ICF), they also must agree to use method(s) of contraception as described above. Postmenopausal female patients must have experienced their last menses more than 1 year prior to the date of ICF
without an alternative medical cause to be classified as not of childbearing potential. |
|
| E.4 | Principal exclusion criteria |
A patient meeting any of the following criteria will be excluded from the study:
1. Patient diagnosed with forms of psoriasis other than chronic plaque (e.g., pustular, erythrodermic or guttate psoriasis) or medication-induced psoriasis (e.g., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).
2. Patient who has previously received investigational or licensed product of tumor necrosis factor (TNF) α inhibitor for any purposes.
3. Patient who has prior exposure to 2 or more biologic agents. Patient with 1 prior biologic agent which is not classified as TNF-α inhibitor (e.g., interleukin [IL]-17, IL-12/23, IL-23 blocker) can be enrolled after 5 half-lives prior to the first administration of the study drug (Day 1).
4. Patient who has allergies to any of the excipients of study drug or materials of device or any other murine and human proteins, or patient with a hypersensitivity to immunoglobulin products.
5. Patient who currently has, or has a history of, any of the following infections:
a) A known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active or carrier state) or syphilis. However, a patient with past hepatitis B virus and/or hepatitis C virus is allowed if resolved.
b) Recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug (Day 1).
c) 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.
d) 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 before Day 1.
6. Patient who currently has, or has a history of, any of the following tuberculosis (TB) conditions:
a) 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.
b) Patient who has had exposure to a person with active TB such as first-degree family members or co-workers.
c) 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.
7. Patient who has a medical condition including one or more of the following:
a) Classified as Class III obesity by WHO classification (body mass index ≥40 kg/m2)
b) Diabetes mellitus considered by the investigator to be clinically significant and uncontrolled, even after insulin treatment.
c) Uncontrolled hypertension (as defined by systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥100 mmHg).
d) Active ongoing inflammatory or autoimmune disease other than chronic plaque psoriasis and psoriatic arthritis, that may confound the evaluation of the effect of the study drug.
e) History of a known malignancy within the previous 5 years prior to the first administration of the study drug (Day 1) except completely excised and cured squamous carcinoma of the uterine cervix in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma.
f) New York Heart Association class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina or clinically significant electrocardiogram [ECG] abnormalities), or myocardial infarction within 24 weeks prior to the first administration of the study drug (Day 1).
g) History of organ transplantation, including corneal graft/transplantation.
h) Any underlying condition (e.g., metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) that, in the opinion of the investigator, significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.
"Refer to the protocol for full list of exclusion criteria"
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The following PK parameters will be assessed between Week 25 and Week 27:
• Area under the concentration-time curve over the dosing interval (AUCtau, 25-27)
• Maximum serum concentration during the dosing interval (Cmax, 25-27) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The following PK parameter will be assessed between Week 25 and Week 27:
• Time to maximum serum concentration during the dosing interval (Tmax, 25-27)
The following PK parameter will be assessed up to Week 52:
• Trough concentration (Ctrough)
The following efficacy endpoints will be assessed until Week 52:
• Mean % improvement from baseline in PASI score
• Proportion of patients achieving at least 50/75/90/100% improvement from baseline in PASI (PASI 50/75/90/100)
• Proportion of patients with an sPGA score on a 5-point scale of clear (0) or almost clear (1)
Safety Endpoints:
Safety assessments will be performed on AEs (including serious AEs), AEs of special interest (injection site reactions, hypersensitivity including anaphylaxis, infections, malignancy, demyelinating diseases, heart failure, and lupus-like syndrome), immunogenicity, vital signs and weight measurement, ECGs, physical examination findings, IGRA, chest X-ray, sign and symptoms of TB, hepatitis B and hepatitis C and HIV status, pregnancy testing, clinical laboratory analyses and prior and concomitant medications monitored throughout the study. Adverse events will be recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 30 |
| 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 | No |
| 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
|
| An EOS visit will occur at Week 52 for patients who completed study treatment. An EW visit will occur if a patient early discontinues from the study for any reason, and every effort should be made to have the patient return to study center for the next planned visit after the last dose of study drug for the assessments planned at the EOS visit. |
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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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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