E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe chronic plaque-type psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to severe psoriasis |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous 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 equivalent efficacy of GP2017 and Humira® in patients with moderate to severe chronic plaque-type psoriasis with respect to PASI75 response rate at Week 16 |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives:
•For treatment period 1: To compare PASI50, PASI75, PASI90 and PASI100 response rates of patients treated with GP2017 and Humira®
•For treatment period 2: to compare efficacy, safety and immunogenicity of pooled data from patients undergoing repeated switches (Groups 1b and 2b) with those from patients constantly treated with GP2017 (Group 1a) and Humira® (Group 2a)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients must be able to understand and communicate with the investigator and comply with the requirements of the study (including administration of s.c. injections) and must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed study consent according to local laws and regulations.
2.Men or women of at least 18 years of age at time of screening
3.Chronic plaque-type psoriasis diagnosed for at least 6 months before randomization
4.Moderate to severe psoriasis as defined at randomization by:
•PASI score of 12 or greater and,
•IGA score of 3 or greater (based on a scale of 0 - 4) and,
•Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater
5.Chronic plaque-type psoriasis patients who have previously received phototherapy or systemic psoriasis therapy at least once or who are candidates for such therapies in the opinion of the investigator.
6.Patient with the following laboratory values obtained during Screening :
a)hemoglobin ≥ 10g/dL
b)white blood count (WBC) ≥3,500/µl/);
c)platelet count ≥ 125,000/µl
d)neutrophils ≥ 2000/µl
e)AST, ALT and AP ≤ 2.5 xULN; .
f)serum creatinine level <176.8 μmol/L (2.0 mg/dL)
g)Negative test for serologic or virologic markers for active or latent Hepatitis B (HBV) and/or Hepatitis C (HCV) infections
h) Negative QuantiFERON®-TB Gold test (QFT)
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E.4 | Principal exclusion criteria |
1.Forms of psoriasis other than chronic plaque-type
2.Ongoing use of prohibited psoriasis treatments
3.Previous exposure to adalimumab
4.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG)
laboratory test (cut-off as defined by central laboratory)
5.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
6. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of treatment of adalimumab
7.Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator
significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy
8.Pre-existing or recent-onset of central of peripheral nervous system demyelinating disorders according to investigator's discretion and taking into account a neurological assessment; patients who are considered to
have an increased risk of developing a demyelinating disease
9.Significant cardiovascular problems, including but not limited to the following: uncontrolled hypertension (≥ 160 systolic/95 diastolic mm Hg), congestive heart failure with known decreased left ventricular
ejection fraction
10.Bi-directional chest X-ray, chest high resolution computerized tomography (HR-CT) scan or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process obtained within 12 weeks prior to randomization, and evaluated by a qualified physician. If subjects do not have an image available at the time of screening, a bi-directional chest X-ray must be done prior to randomization after it is fairly certain the patient meets the other inclusion/exclusion criteria in order to minimize unnecessary exposure to X-ray radiation for patients.
11.History of an ongoing, chronic or recurrent infectious disease. History of active TB. Presence of latent (inactive) TB detected by imaging or by the QuantiFERON®-TB Gold test (QFT) at screening.
12.Active systemic infections during the last two weeks (exception: common cold) prior to randomization and any infections that reoccur on a regular basis; patients with a history or evidence of opportunistic infections
13.Past medical history record of infection with human immunodeficiency virus (HIV)
14.History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months before screening, and except for carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed)
15.Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the PASI 75 response rate (proportion of subjects showing at least a 75% improvement PASI at Week 16 in Treatment Period 1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 16 of Treatment Period 1 |
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E.5.2 | Secondary end point(s) |
Treatment Period 1:
•PASI 50, 75, 90 and 100 response rates at Weeks 1, 3, 5, 7, 9, 11, 13, 15, 16, and 17
•Percentage change from baseline in PASI scores at Weeks 1, 3, 5, 7, 9, 11, 13, 15, 16, and 17
•IGA, i.e. proportion of patients achieving clear (0) or almost clear (1) disease state (scale of 0 – 4) at Weeks 1, 3, 5, 7, 9, 11, 13, 15, 16, and 17
•Change from baseline in IGA at Weeks 1, 3, 5, 7, 9, 11, 13, 15, 16, and 17
•Patient's health-related quality of life (HRQoL) as assessed with regard to relative changes in the DLQI, EQ-5DTM-5L and HAQ-DI© (PsA patients only) from baseline to Week 11 and 16; proportion of patients achieving a DLQI of 0 or 1 from baseline in Week 11 and 16.
Treatment Period 2:
•PASI 50, 75, 90 and 100 response rates at Weeks 23, 29, and 35
•Percentage change from Week 17 in PASI scores at Weeks 23, 29, and 35
•IGA, i.e. proportion of patients achieving clear (0) or almost clear (1) disease state (scale of 0 – 4) at Weeks 23, 29, and 35
•Change from Week 17 in IGA at Weeks 23, 29, and 35
•HRQoL as assessed with regard to changes in the DLQI and EQ-5DTM -5L and HAQ-DI© (only in patients with a medical history of PsA) from Week 17 to Weeks 23, 29, and 35; proportion of patients achieving a DLQI of 0 or 1 in Weeks 23, 29 and 35.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Multiple time points, main timepoints being week 17 and week 35 |
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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 | Yes |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 70 |
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 |
France |
Japan |
Romania |
Slovakia |
Germany |
India |
Lithuania |
Poland |
Russian Federation |
United States |
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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 | 7 |