Hulio Interchangeability to Humira®, Comparing Pharmacokinetics, Efficacy, Safety and Immunogenicity

Study Overview
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Brief Summary
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Hulio is a monoclonal antibody currently approved as a biosimilar to European Union approved and United States (US)-Licensed Humira. This is a multicenter, randomized blinded, parallel group, interchangeability study in subjects with moderate to severe chronic plaque psoriasis, undergoing repeated switches between Humira and Hulio. The study is designed to confirm the pharmacokinetic equivalence of alternating between the use of Humira and Hulio and, Humira without such alternation or switch, in accordance with the US Food and Drug Administration Guidance for Industry, Considerations in Demonstrating Interchangeability with a Reference Product. The study will also assess safety, efficacy and immunogenicity between these two groups.

Official Title
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A Multicenter, Randomized, Blinded, Parallel Group, Interchangeability Study in Moderate to Severe Chronic Plaque Psoriasis Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity Between Subjects Receiving Humira® Pre Filled Syringe (40 mg) Continuously and Subjects Undergoing Repeated Switches Between Humira® Pre Filled Syringe (40 mg) and Hulio Pre-filled Syringe (40 mg)

Conditions
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Moderate Chronic Plaque Psoriasis, Severe Chronic Plaque Psoriasis

Intervention / Treatment
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* Biological: Humira 40 MG in Prefilled Syringe
* Biological: Hulio 40 MG in Prefilled Syringe / Humira 40 MG in Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: Able to understand and voluntarily provide written informed consent to participate in the study Aged 18 to 75 years, inclusive, at the time of Screening Has moderate to severe chronic plaque psoriasis for at least 6 months prior to screening and that has involved body surface area ≥10%, PASI ≥12, and static Physicians Global Assessment (sPGA) ≥3 (moderate) at Screening and at Baseline Has stable disease for at least 2 months (i.e., without significant changes as defined by the principal investigator [PI] or designee) Is a candidate for systemic therapy or phototherapy Has a previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy, including methotrexate, cyclosporine, psoralen plus ultraviolet light A (PUVA), and ultraviolet light B (UVB) Willing to follow the contraception requirement, based on the childbearing potential. Exclusion Criteria: Subjects must not be enrolled in the study if they meet any of the following criteria: 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 Prior and concomitant medications: Has prior use of any of the medications specified in the CTP within specified time periods or will require use during the study: 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 Other medical conditions: Known chronic or relevant acute TB 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 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 Has any active and serious infection or history of infections 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 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. The subjects should be excluded if they have the following laboratory abnormalities Hemoglobin <9 g/dL Platelet count <100 000/mm3 White blood cell count <3000 cells/mm3 Aspartate aminotransferase and/or alanine aminotransferase that is persistently ≥2.5 × the upper limit of normal. (Persistently indicates elevated transaminases, at least on two separate occasions) Creatinine clearance <50 mL/min (Cockcroft Gault formula) Has severe progressive or uncontrolled, clinically significant disease that in the judgment of the PI or designee renders the subject unsuitable for the study Has moderate to severe heart failure (New York Heart Association [NYHA] Class III/IV) Has a history of hypersensitivity to the active substance or to any of the excipients of Humira or Hulio Is pregnant or nursing (lactating) woman 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 Is unable to follow study instructions and comply with the protocol in the opinion of the PI or designee.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Humira continuously<br>Subjects receive Humira continuously both during Run-in period and Randomized interchangeable treatment period. Run-in Period: Subjects will receive Humira (initial dose of 80 mg [2 × 40 mg]; Day 1 administered subcutaneously (SC), followed by 40 mg SC given every other week starting 1 week after the initial dose (last dose at Week 10). Randomized interchangeable treatment period: Subjects continue to receive Humira (40 mg every other week) until Week 26 | Biological: Humira 40 MG in Prefilled Syringe<br>* Humira (40 mg every other week)<br>|
| Experimental: Repeated switches Humira - Hulio<br>Subjects will receive Humira in Run-in period & undergo repeated switches between Humira Hulio during randomized interchangeable treatment period Randomized interchangeable treatment period: Subjects undergo repeated switches between Humira and Hulio between week 12 to week 26. Hulio (40 mg every other week) at Week 12 and Week 14 Humira (40 mg every other week) at Week 16 and Week 18, and Hulio (40 mg every other week) at Week 20, Week 22, Week 24 and Week 26. | Biological: Hulio 40 MG in Prefilled Syringe / Humira 40 MG in Prefilled Syringe<br>* • Subjects will receive Humira (initial dose of 80 mg [2 × 40 mg]; Day 1 administered subcutaneously (SC), followed by 40 mg SC given every other week starting 1 week after the initial dose (last dose at Week 10). Hulio (40 mg every other week) at Week 12 and Week 14 Humira (40 mg every other week) at Week 16 and Week 18, and Hulio (40 mg every other week) at Week 20, Week 22, Week 24 and Week 26.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoints: Pharmacokinetics (PK) - AUC | AUCτ, 26-28 (Area under the adalimumab concentration-time curve [AUC] over the dosing interval of Week 26-28) | Week 26 - 28 | 
| Primary Endpoints: Pharmacokinetics (PK) - Cmax | Cmax, 26-28 (Maximum observed adalimumab concentration during the dosing interval Week 26-28). | Week 26 - 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adalimumab, pharmacokinetics, plaque psoriasis