| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic plaque-type psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inflammatory skin disorder with itchy, well-demarcated circular-to-oval bright red/pink elevated lesions with overlying white or silvery scale, distributed over extensor body surfaces and the scalp. |
|
| 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 |
| The primary objective of the study is to demonstrate equivalence in measures of efficacy between M923 (test) and EU-licensed Humira (referred to as the Reference Protein Product (EU RPP) in subjects with moderate to severe chronic plaque-type psoriasis. |
|
| E.2.2 | Secondary objectives of the trial |
1. Evaluate the continued efficacy safety, immunogenicity, and tolerability of M923 compared with EU RPP
2. Evaluate the transition from EU RPP to M923 based on safety and immunogenicity compared with continuous use of EU RPP
3. Evaluate concentrations over time |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects must be ≥ 18 years old at the time of screening
2. Must be able to understand and communicate with the investigator and comply with the requirements of the study (including administration of SC injections at
home) and must give a written, signed, and dated informed consent before any
study-related activity is performed. Where relevant, a legal representative will
also sign the informed study consent according to local laws and regulations
3. Chronic plaque-type psoriasis diagnosed for at least 6 months before screening
4. Stable plaque-type psoriasis, defined as no significant change in lesional area or
severity, for a period of 2 months or more before screening
5. History of receipt of or candidate for systemic therapy or phototherapy with active
plaque-like psoriasis despite topical therapy
6. Moderate to severe psoriasis at screening and baseline (Visit 2), defined as:
a. PASI score ≥ 12
b. sPGA score ≥ 3 (based on a scale of 0 - 5)
c. Body Surface Area (BSA) affected by plaque-type psoriasis ≥ 10%
7. Must be willing and able to self-administer SC injections or have a caregiver available to administer injections
8. Male subjects must either abstain from sexual intercourse or use a condom in addition to having their female partner use another form of contraception such as an intra-uterine device, barrier method (eg, diaphragm or sponge; female condom not permitted) with spermicide, oral
contraceptive, injectable progesterone, sub-dermal implant, unless their partners
are infertile or surgically sterile from the time of the first administration of IP
until completion of study procedures. Alternatively, male subjects may have been vasectomized, with confirmation of sterility.
9. Female subjects must have a negative pregnancy test at screening and baseline
and must not be lactating. Female subjects must also meet one of the conditions
below for the entire duration of the study:
a. Abstain from sexual intercourse
b. Use a method of contraception, as described for female partners in Inclusion Criterion 8, and have their male partner use a condom until 5 months after the last administration of the IP
c. Be of non-childbearing potential, confirmed at screening by fulfilling 1 of
the following criteria:
i. Postmenopausal, defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with
follicle-stimulating hormone levels drawn during screening within the laboratory-defined postmenopausal range or postmenopausal with amenorrhea for at least 24 months and on hormonal replacement therapy.
ii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, bilateral tubal ligation (BTL; with no subsequent pregnancy at least 1 year from BTL), or bilateral salpingectomy |
|
| E.4 | Principal exclusion criteria |
1. Presence of forms of psoriasis other than chronic plaque-type (eg, pustular, erythrodermic, or guttate psoriasis)
2. History of or current drug-induced psoriasis (eg, from beta-blockers or lithium).
3. Presence of other skin conditions, including skin infections, which would interfere
with assessment of psoriasis
4. Presence of chronic or ongoing medical conditions other than psoriasis for which
systemic corticosteroids were used in the last year prior to screening, eg, asthma
5. Presence of other inflammatory conditions other than psoriasis or psoriatic
arthritis, eg, rheumatoid arthritis, gout, inflammatory bowel disease
6. Subject must have no major deviations regarding concomitant medication, such as prior use of systemic tumor necrosis factor (TNF) inhibitor therapy, investigational or licensed (ie, other investigational biosimilar TNF inhibitor therapy exposure is not permitted), or 2 or more non-TNF biologic therapies required concomitantly
7. Ongoing use of prohibited psoriasis treatments (eg, prohibited topical
corticosteroids, systemic corticosteroids, ultraviolet (UV) therapy including excessive
sun exposure, immunosuppressant therapy, including MTX); washout periods
detailed in Section 10.4 must be followed
8. Ongoing use of other non-psoriasis prohibited treatments; washout periods
detailed in Section 10.4 must be followed. All other prior non-psoriasis concomitant treatments must be on a stable dose for at least 4 weeks before baseline (Visit 2)
9. All other prior non-psoriasis concomitant treatments must be on a stable dose for
at least 4 weeks before baseline
10. Laboratory abnormalities at screening deemed clinically significant by the investigator and/or:
a. Hemoglobin < 8 g/dL for women or 8.5 g/dL for men
b. White blood cell count < 3.5 x 109/L
c. Platelet count < 120 x 109/L
d. Aspartate transaminase or alanine transaminase > 1.5 times the upper limit of
normal
e. Creatinine > 1.5 mg/dL if < 65 years old, or > upper limit of normal if ≥ 65
years old
11. Severe, progressive, or uncontrolled renal, hepatic, metabolic, hematologic,
gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease, including
pleural effusions or ascites, which in the opinion of the investigator or sponsor
pose an unacceptable safety risk
12. History of latex allergy
13. History of or current signs or symptoms or diagnosis of a demyelinating disorder
14. History of or current Class III or IV New York Heart Association congestive heart
failure
15. History or current signs, symptoms, or diagnosis of lymphoproliferative disorders,
lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma
16. Current malignancy or history of any malignancy except adequately treated or
excised non metastatic basal cell or squamous cell cancer of the skin or cervical
carcinoma in situ; no more than 3 lifetime basal cell and squamous cell carcinomas permitted
17. Chronic infections, recurrent infections (3 or more of the same infection requiring
anti-infective treatment in any rolling 12 month period); any recent infection
requiring hospitalization or any infection requiring parenteral anti-infective
therapy within 30 days or oral infective therapies within 14 days of baseline (Visit
2); herpes zoster within 6 months of baseline or more than 2 lifetime episodes of
herpes zoster; or history of systemic fungal infection or opportunistic infection
(eg, coccidiomycosis, histoplasmosis, toxoplasmosis)
18. History of or presence of human immunodeficiency virus (HIV), or Hepatitis B
(HBV) or C virus (HCV)
19. History of active tuberculosis (TB) or untreated or inadequately treated latent TB. Subject must have a negative QuantiFERON, T-spot or purified protein derivative (PPD), and a radiograph or comparable imaging with negative finding for TB or other similar infections at the Screening visit or within 3 months prior to Screening visit
20. Subject has been exposed to an IP within 30 days prior to enrollment or is
scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
21. Subject is a family member or employee of the investigator or site staff or study
team |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary outcome measure is the Psoriasis Area and Severity Index 75%
improvement (PASI75) response rate at Week 13 in subjects treated with M923 vs
Humira. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
1. Proportion of subjects with response by static Physician Global Assessment (sPGA) of clear or almost clear (6-point scale) at Week 16 in subjects treated with M923 vs EU RPP
2. PASI50, PASI75, PASI90, and sPGA response rates over time in subjects treated with M923 or EU RPP
3. Absolute PASI score over time in subjects treated with M923 and EU RPP
4. Health-related quality of life during treatment with M923 and EU RPP based on
the Dermatology Life Quality Index (DLQI) and the EuroQoL 5-Dimension
Health Status Questionnaire (EQ-5D-5L)
Safety:
1. Clinical safety and tolerability of M923 compared with EU RPP as
assessed by vital signs, clinical laboratory results, electrocardiograms (ECGs),
and AEs (including serious AEs [SAEs], withdrawal from the study besause of an AE, discontinuation of study-specific therapy because of an AE, and injection site reactions)
2. Clinical safety and tolerability of the transitions between EU RPP and M923 (occurring twice in arm B2) compared with continuous use of EU RPP (arm B1)
Pharmacokinetics and Immunogenicity:
1. Exposure to M923 and EU RPP assessed as serum levels collected periodically throughout the treatment period
2. Immunogenicity of M923 and EU RPP assessed as proportion experiencing
seroconversion, titer of anti-drug antibody (ADA) levels over time, and neutralizing ADA
3. Immunogenicity, as evidenced by the presence of ADAs, following the transition from EU RPP to M923 compared with continuous use of EU RPP assessed as proportion of subjects experiencing seroconversion; titer of ADA levels over time, and neutralizing ADA over time |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Over the course of the study;
|
|
| 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 | 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 | No |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | Yes |
| 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 | 56 |
| 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 |
| Czech Republic |
| Estonia |
| Germany |
| Hungary |
| Latvia |
| Poland |
| Serbia |
| Slovakia |
| Turkey |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 20 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 20 |
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