E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe chronic plaque psoriasis |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
|
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 interchangeability of Hulio and Humira by examining adalimumab steady-state PK in a switching arm (following 3 switches between Humira and Hulio) as compared to a non-switching arm (receiving only Humira). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate other serum adalimumab PK parameters, efficacy, immunogenicity, safety, and tolerability, in the switching arm and the non-switching arm. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able to understand and voluntarily provide written informed consent to participate in the study 2. Aged 18 to 75 years, inclusive, at the time of Screening 3. Has moderate to severe chronic plaque psoriasis for at least 6 months prior to screening and that has involved body surface area (BSA) ≥10%, PASI ≥12, and static Physicians Global Assessment (sPGA) ≥3 (moderate) at Screening and at Baseline 4. Has stable disease for at least 2 months (i.e., without significant changes as defined by the principal investigator [PI] or designee) 5. Is a candidate for systemic therapy or phototherapy 6. Has a previous failure, inadequate response, intolerance, or contraindication to at least one conventional antipsoriatic systemic therapy, including methotrexate, cyclosporine, psoralen plus ultraviolet light A (PUVA), and ultraviolet light B (UVB) 7. Willing to follow the contraception requirement, based on the childbearing potential. |
|
E.4 | Principal exclusion criteria |
1. Has been diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, other skin conditions (e.g., eczema), or other systemic autoimmune disorder/ inflammatory disease at the time of the Screening visit that would interfere with evaluations of the effect of the study treatment of psoriasis 2. Prior and concomitant medications: Has prior use of any of the following medications within specified time periods or will require use during the study: a) Topical medications within 2 weeks of baseline (Week 1) b) PUVA phototherapy and/or UVB phototherapy within 4 weeks prior to Baseline visit c) Nonbiologic psoriasis systemic therapies (eg, cyclosporine, methotrexate, and acitretin) within 4 weeks prior to Baseline visit d) Any prior or concomitant adalimumab therapy, either approved or investigational e) Any systemic steroid in the 4 weeks prior to Baseline Visit 3. Has received live or attenuated vaccines during the 4 weeks prior to Screening or has the intention of receiving a live or attenuated vaccine at any time during the study 4. Other medical conditions: Known chronic or relevant acute TB; IGRA TB test or PPD skin test will be performed according to the labelling for Humira. If the result is positive, patients may participate in the trial if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active TB. If latent TB is confirmed, then treatment must have been initiated before treatment in the study and continued according to local country guidelines. 5. Has an underlying condition (including, but not limited to, metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal) which, in the opinion of the PI or designee, significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy. 6. Has a planned surgical intervention during the duration of the study and which, in the opinion of the PI or designee, will put the subject at further risk or hinder the subject’s ability to maintain compliance with study treatment and the visit schedule 7. Has any active and serious infection or history of infections. 8. Is positive for human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B surface antigen (HbsAg) or is positive for hepatitis B core antibody (HbcAb) at Screening 9. Has laboratory abnormalities, including but not limited to clinically significant hematological abnormalities, that, in the opinion of the PI or designee, could cause this study to be detrimental to the subject. 10. Has severe progressive or uncontrolled, clinically significant disease that in the judgment of the PI or designee renders the subject unsuitable for the study 11. Has a history of malignancy within 5 years except for adequately treated cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma 12. Has an active neurological disease, such as multiple sclerosis, Guillain-Barré syndrome, optic neuritis, and transverse myelitis, or a history of neurologic symptoms suggestive of central nervous system demyelinating disease 13. Has moderate to severe heart failure 14. Has a history of hypersensitivity to the active substance or to any of the excipients of Humira or Hulio 15. Is pregnant or nursing (lactating) woman 16. Has evidence (as assessed by the PI or designee using good clinical judgment) of alcohol or drug abuse or dependency up to 5 years prior to Screening. 17. Is unable to follow study instructions and comply with the protocol in the opinion of the PI or designee. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints include the assessment of below mentioned pharmacokinetic parameters: - AUCτ, 26-28 (Area under the adalimumab concentration-time curve [AUC] over the dosing interval of Week 26-28) - Cmax, 26-28 (Maximum observed adalimumab concentration during the dosing interval Week 26-28).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
AUCτ- over the dosing interval of Week 26-28 Cmax - during the dosing interval Week 26-28 |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are: 1. Other adalimumab PK parameters, including Tmax, 26-28 (Time to maximum observed adalimumab concentration during the dosing interval Week 26-28) and Cmin, 26-28 (Minimum observed adalimumab concentration during the dosing interval Week 26-28) and Ctrough obtained at scheduled PK sampling time points. 2. Proportion of Psoriasis Area and Severity Index (PASI) 50, PASI 75, PASI 90 and PASI 100 responders at Week 28 3. Proportion of static Physician’s Global Assessment (sPGA) success (clear or almost clear) at Week 28. 4. Safety measures characterized by type, incidence, severity, timing, seriousness and relatedness of treatment-emergent adverse events (TEAEs) including injection site reactions, hypersensitivity reactions, heart failure, malignancies, serious infections including tuberculosis (TB) and laboratory test abnormalities 5. Incidence of positive anti-drug antibody (ADA) and neutralizing antibody (NAb) response and ADA titers at Week 28 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. between Weeks 26 and 28 2. at Week 28 3. at Week 28 4. From first dose of study medication to last visit 5. at Week 28 |
|
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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 |
|
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
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 | 36 |
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
|
End of study will be considered when all the subjects complete the safety follow-up assessment period |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 6 |