| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic skin inflammatory disease |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| 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 |
| The primary objective of this study is to assess the equivalence of MYL-1401A to Humira® with regards to efficacy at Week 16 in subjects with moderate-to-severe chronic plaque psoriasis. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To compare the efficacy of MYL-1401A and Humira® in subjects with moderate to severe chronic plaque psoriasis at Weeks 16, 24, and 52.
• To compare the safety and tolerability of MYL-1401A and Humira®
• To compare the immunogenicity of MYL-1401A and Humira®
• To assess steady-state pharmacokinetics of MYL-1401A and Humira® |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each subject must meet all of the following criteria to be enrolled in this study:
1. Subject has signed the ICF and documentation as required by relevant competent authorities and is able to understand and adhere to the visit schedule and study requirements
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
a) 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 or phototherapy
6. Subject has had a previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy (e.g. methotrexate, cyclosporine, psoralen plus ultra violet [UV] A [PUVA], UVB)
7. Subject is naïve to adalimumab therapy, approved or investigational 8. For female subjects of childbearing potential, a negative serum pregnancy test during Screening and a negative urine pregnancy test at Baseline
Note: Childbearing potential is defined as any female subject who has experienced menarche and is not postmenopausal (defined as amenorrhea for at least 12 consecutive months), or has not undergone surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (however, women who have been surgically sterilized by bilateral oophorectomy or bilateral tubal ligation within the last 6 months must also have a negative pregnancy test at Screening to be considered of nonchildbearing potential). All other women will be considered to be of childbearing potential and must be using an acceptable contraceptive method as described in detail in Exclusion Criterion no. 9.
9. Fertile male and female subjects participating in heterosexual relations must be willing to use adequate contraception (i.e. 2 effective methods, one of which must be a physical barrier method) from Screening until 5 months after their last dose of study treatment; or must be sexually inactive by abstinence, which is consistent with the preferred and usual lifestyle of the subject
a) Effective forms of contraception are a condom, an established form of hormonal contraception, a diaphragm or cervical/vault cap or an intrauterine device. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
b) Sterile males and females and subjects who have same-sex sexual relations do not have to use contraception. Sterile males and females must be surgically sterile for at least 6 months or postmenopausal (females) at least 2 years. |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria will be excluded from the study:
Skin disease related:
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
Prior and concomitant medications:
2. Subject has used any of the following medications within specified time periods or will require their use during the study:
a) Topical medications within 2 weeks of Screening
b) PUVA phototherapy and/or UVB phototherapy within 4 weeks of Screening
c) Nonbiologic systemic therapies within 4 weeks of Screening (e.g. cyclosporine, methotrexate, and acitretin)
d) Any prior or concomitant adalimumab therapy, approved or investigational
e) Any other investigational agent within 90 days or 5 half-lives of Screening (whichever is longer)
f) Any systemic steroid in the 4 weeks prior to Screening
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
Other medical conditions:
4. Subject has a positive test for 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
A positive test for TB during Screening is defined as either:
- Positive purified protein derivative test (≥5 mm of induration at 48 to 72 hours after test is placed) OR- Positive IGRA.
Refer to protocol for Note Positive IGRA conditions.
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 any 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. Note: Subjects receiving topical antibiotics for facial acne do not need to be excluded.
- 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 HIV or HCV antibody or HBsAg or is positive for HBcAb 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 a laboratory abnormality that, in the opinion of the investigator, could cause this study to be detrimental to the subject (focus on Hemoglobin, Platelet count,, White blood cell count, ASAT/ALAT, Creatinine clearance)
11. Subject has severe progressive or uncontrolled, clinically significant disease that in the judgment of the investigator renders the subject unsuitable for the study
12. 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
13. 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
14. Subject has moderate to severe heart failure (NYHA class III/IV)
15. Subject has a history of hypersensitivity to the active substance or to any of the excipients of Humira® or MYL-1401A
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation
17. Evidence (as assessed by the investigator using good clinical judgment) of alcohol or drug abuse or dependency at the time of Screening, for the 5 years prior to Screening or during the study
18. Subject is unable to follow study instructions and comply with the protocol in the opinion of the investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the proportion of subjects showing at least a 75% improvement in PASI (PASI 75 response rate) at Week 16. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- The key secondary efficacy endpoints are:
• Percent improvement in PASI from Baseline to Week 16
• Number and percentage of subjects achieving sPGA responses of clear (0) or almost clear (1) at Week 16
- The additional secondary efficacy endpoints are:
• PASI 75 response rate at Weeks 24 and 52
• PASI 50, 90, and 100 response rates at Weeks 16, 24, and 52
• Percent improvement in PASI from Baseline to Weeks 24 and 52
• Number and percentage of subjects achieving sPGA responses of clear (0) or almost clear (1) at Weeks 24 and 52
• Change from Baseline in percentage of BSA involvement at Weeks 16, 24, and 52
• Change from Baseline in quality of life as measured by DLQI scores at Weeks 16, 24, and 52
- The safety endpoints are:
• Frequency, type and severity of AEs, including ADRs
• Frequency and severity of ISRs
• Detection of antidrug antibodies to MYL-1401A or Humira® at Weeks 4, 8, 12, 16, 24, 42, 52, and follow-up
• Routine safety parameters, including laboratory safety, vital sign measurements, 12 lead ECG and chest x-ray results, and physical examination findings
- Pharmacokinetic Endpoint
The PK endpoint is the serum trough concentrations of MYL-1401A and Humira®.
- The exploratory endpoints are:
• Concentration of PD marker hs-CRP at Week 16
• Change from Baseline in RAPID3 at Week 12 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be assessed during the whole study till Follow-up visit (Weeks 4, 8, 12, 16, 24, 42, 52, and follow-up). Please note not all endpoints will be assessed on each of the visits.
|
|
| 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 | 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 | 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 | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| After Week 24, the study will have a single-blind design. |
|
| 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 | 2 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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 |
| Canada |
| Estonia |
| Germany |
| Hungary |
| India |
| Poland |
| Russian Federation |
| Ukraine |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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