Clinical trial NCT02714322: MYL-1401A Efficacy and Safety Comparability Study to Humira®
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Arthritis, Psoriatic
Keywords: Adalimumab
Biologics
Biosimilar
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mylan GmbH
First posted: 2016-03-21
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Subject has signed the informed consent form
2. Subject is aged 18 to 75 years, inclusive, at time of Screening
3. 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
4. Subject has had stable disease for at least 2 months (i.e. without significant changes as defined by the investigator)
5. Subject is a candidate for systemic therapy
6. Subject has had a previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy
7. Subject is naïve to adalimumab therapy, approved or investigational
8. For females of childbearing potential, a negative serum pregnancy test during Screening and a negative urine pregnancy test at Baseline

Exclusion Criteria:

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. Subject has a history of clinically significant hematological abnormalities, including cytopenias (e.g. thrombocytopenia, leukopenia)
10. Subject has severe progressive or uncontrolled, clinically significant disease that in the judgment of the investigator renders the subject unsuitable for the study
11. 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
12. 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
13. Subject has moderate-to-severe heart failure (New York Heart Association class III/IV)
14. Subject has a history of hypersensitivity to the active substance or to any of the excipients of Humira® or MYL-1401A
15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation
16. Evidence of alcohol or drug abuse or dependency at the time of Screening, for the 5 years prior to Screening or during the study
17. Subject is unable to follow study instructions and comply with the protocol in the opinion of the investigator

Primary outcomes:
measure: Percent improvement in PASI from Baseline
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Proportion of subjects showing at least a 75% improvement in PASI (PASI 75 response rate)
timeFrame: Week 12
measure: Number of subjects achieving static Physician's Global Assessment (sPGA) responses of clear (0) or almost clear (1)
timeFrame: Week 12
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Mylan Investigational Site 102
city: Plovdiv
country: Bulgaria
facility: Mylan Investigational Site 105
city: Sevlievo
country: Bulgaria
facility: Mylan Investigational Site 101
city: Sofia
country: Bulgaria
facility: Mylan Investigational Site 100
city: Sofia
country: Bulgaria
facility: Mylan Investigational Site 103
city: Tallinn
country: Estonia
facility: Mylan Investigational Site 107
city: Tallinn
country: Estonia
facility: Mylan Investigational Site 108
city: Tallinn
country: Estonia
facility: Mylan Investigational Site 109
city: Tallinn
country: Estonia
facility: Mylan Investigational site 110
city: Tartu
country: Estonia
facility: Mylan Investigational Site 106
city: Tartu
country: Estonia
facility: Mylan Investigational SIte 112
city: Budapest
country: Hungary
facility: Mylan Investigational Site 127
city: Budapest
country: Hungary
facility: Mylan Investigational Site 128
city: Debrecen
country: Hungary
facility: Mylan Investigational Site 125
city: Gyula
country: Hungary
facility: Mylan Investigational Site 129
city: Szekszárd
country: Hungary
facility: Mylan Investigational Site 126
city: Bialystok
country: Poland
facility: Mylan Investigational Site 131
city: Bialystok
country: Poland
facility: Mylan Investigational Site 137
city: Iwonicz-Zdroj
country: Poland
facility: Mylan Investigational Site 135
city: Krakow
country: Poland
facility: Mylan Investigational Site 140
city: Lodz
country: Poland
facility: Mylan Investigational Site 139
city: Olsztyn
country: Poland
facility: Mylan Investigational Site 133
city: Poznan
country: Poland
facility: Mylan Investigational Site 138
city: Warsaw
country: Poland
facility: Mylan Investigational Site 136
city: Wroclaw
country: Poland
facility: Mylan Investigational Site 130
city: Wroclaw
country: Poland
facility: Mylan Investigational Site 132
city: Wroclaw
country: Poland
facility: Mylan Investigational Site 134
city: Kazan
country: Russian Federation
facility: Mylan investigational site 156
city: Penza
country: Russian Federation
facility: Mylan Investigational site 155
city: Ryazan
country: Russian Federation
facility: Mylan Investigational Site 148
city: St. Petersburg
country: Russian Federation
facility: Mylan Investigational Site 149
city: Kharkiv
country: Ukraine
facility: Mylan Investigational site 159
city: Uzhhorod
country: Ukraine
facility: Mylan investigational site 161
Study officials:
affiliation: Mylan
name: Abhijit Barve, MD
role: STUDY_CHAIR
References: