MYL-1401A Efficacy and Safety Comparability Study to Humira®

Study Overview
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Brief Summary
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To assess the equivalence of MYL-1401A to Humira® with regards to efficacy in subjects with moderate-to-severe chronic plaque psoriasis

Detailed Description
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Eligible subjects will be randomly assigned based on predefined stratification factors of weight, geographic region, and presence of psoriatic arthritis: Randomization is 2:1 to MYL-1401A or Humira®, respectively. The study will be conducted in the outpatient setting and comprises 3 periods: a screening period of up to 4 weeks, a 52-week treatment period, and a safety follow-up for 8 weeks. A subject will be considered to have completed the study once they have completed the 52-week treatment period and the 8-week follow-up visit.

Official Title
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Multicenter, Double-Blind, Randomized, 2-Arm, Parallel-Group, Equivalence Study Evaluating Efficacy and Safety Similarity of Mylan Adalimumab (MYL-1401A) Compared With Humira® in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis

Conditions
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Psoriasis, Arthritis, Psoriatic

Intervention / Treatment
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* Biological: MYL-1401A (Adalimumab)
* Biological: Humira® (Adalimumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed the informed consent form Subject is aged 18 to 75 years, inclusive, at time of Screening Subject has had moderate-to-severe chronic plaque psoriasis for at least 6 months Subject has involved BSA ≥10%, PASI ≥12, and sPGA ≥3 (moderate) at Screening and at Baseline Subject has had stable disease for at least 2 months (i.e. without significant changes as defined by the investigator) Subject is a candidate for systemic therapy Subject has had a previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy Subject is naïve to adalimumab therapy, approved or investigational For females of childbearing potential, a negative serum pregnancy test during Screening and a negative urine pregnancy test at Baseline Exclusion Criteria: Subject 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 on psoriasis Subject has used any of the following medications within specified time periods or will require their use during the study: Topical medications within 2 weeks before the end of the screening period oral psoralen with ultraviolet A (PUVA) phototherapy and/or ultraviolet B (UVB) phototherapy within 4 weeks before the end of the screening period Nonbiologic systemic therapies within 4 weeks before the end of the screening period (e.g. cyclosporine, methotrexate, and acitretin) Any prior or concomitant adalimumab therapy, approved or investigational Any other investigational agent within 90 days or 5 half-lives of Screening (whichever is longer) Any systemic steroid in the 4 weeks before the end of the screening period Note: Low-potency topical corticosteroids applied to the palms, soles, face, and intertriginous areas are permitted during study participation Subject has received live vaccines during the 4 weeks prior to Screening or has the intention of receiving a live vaccine at any time during the study Subject has a positive test for tuberculosis (TB) during Screening or a known history of active or latent TB, except documented and complete adequate treatment of TB or initiation (>1 month) of adequate prophylaxis of latent TB, with an isoniazid-based regimen Subjects with a positive purified protein derivative (PPD) and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Interferon-γ release assays (IGRA) Subjects with a positive PPD test without a history of Bacillus Calmette-Guérin vaccination or subjects with a positive or indeterminate IGRA are allowed if they have all of the following: No symptoms or signs of active TB, including a negative chest x-ray within 3 months prior to the first dose of study treatment Documented history of completion of adequate treatment of TB or initiation (>1 month) of adequate prophylaxis of latent TB, with an isoniazid-based regimen prior to receiving study treatment in accordance with local recommendations 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 subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy Subject has a planned surgical intervention during the duration of the study except those related to the underlying disease and which, in the opinion of the investigator, will not put the subject at further risk or hinder the subject's ability to maintain compliance with study treatment and the visit schedule Subject has an active and serious infection or history of infections as follows: Any active infection: For which nonsystemic anti-infectives were used within 4 weeks prior to randomization. Requiring hospitalization or systemic anti-infectives within 8 weeks prior to randomization Recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject Invasive fungal infection or mycobacterial infection Opportunistic infections, such as listeriosis, legionellosis, or pneumocystis Subject is positive for human immunodeficiency virus, hepatitis C virus antibody or hepatitis B surface antigen (HBsAg) or is positive for hepatitis B core antibody and negative for HBsAg at Screening Subject has a history of clinically significant hematological abnormalities, including cytopenias (e.g. thrombocytopenia, leukopenia) Subject has severe progressive or uncontrolled, clinically significant disease that in the judgment of the investigator renders the subject unsuitable for the study Subject has history of malignancy within 5 years except adequately treated cutaneous squamous or basal cell carcinoma, in situ cervical cancer or in situ breast ductal carcinoma Subject has active neurological disease such as multiple sclerosis, Guillain-Barré syndrome, optic neuritis, transverse myelitis, or history of neurologic symptoms suggestive of central nervous system demyelinating disease Subject has moderate-to-severe heart failure (New York Heart Association class III/IV) Subject has a history of hypersensitivity to the active substance or to any of the excipients of Humira® or MYL-1401A Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation Evidence of alcohol or drug abuse or dependency at the time of Screening, for the 5 years prior to Screening or during the study Subject is unable to follow study instructions and comply with the protocol in the opinion of the investigator

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 |
| --- | --- |
| Experimental: MYL-1401A (Adalimumab)<br>MYL-1401A initial dose of 80 mg administered subcutaneously (sc), followed by 40 mg sc given every other week starting 1 week after the initial dose | Biological: MYL-1401A (Adalimumab)<br>* MYL-1401A initial dose of 80 mg administered subcutaneously (sc), followed by 40 mg sc given every other week starting 1 week after the initial dose<br>|
| Active Comparator: Humira® (Adalimumab)<br>Humira® initial dose of 80 mg administered subcutaneously (sc), followed by 40 mg sc given every other week starting 1 week after the initial dose | Biological: Humira® (Adalimumab)<br>* Humira® initial dose of 80 mg administered sc, followed by 40 mg sc given every other week starting 1 week after the initial dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent improvement in PASI from Baseline |  | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects showing at least a 75% improvement in PASI (PASI 75 response rate) |  | Week 12 | 
| Number of subjects achieving static Physician's Global Assessment (sPGA) responses of clear (0) or almost clear (1) |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adalimumab, Biologics, Biosimilar