E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque Psoriasis |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Plaque Psoriasis |
|
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 | 19.0 |
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 |
To demonstrate the therapeutic equivalence of ONS-3010 (adalimumab biosimilar) compared to Humira (adalimumab) in patients with plaque psoriasis |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability, and immunogenicity of ONS-3010 compared to Humira in patients with plaque psoriasis |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A pharmacodynamic sub-study of
A Randomized, Double-Blind, Multicenter, Equivalence Study of ONS-3010 and Humira® for the Treatment of Patients with Moderate to Severe Plaque Psoriasis (ONS-3010-002)
and
A Randomized, Double-Blind, Multicenter Extension Study Comparing Long-Term Safety and Efficacy, including Interchangeability (Switch), of ONS-3010 and Humira® in Patients with Plaque Psoriasis (ONS-3010-003)
This sub-study is intended to investigate the pharmacodynamic effects of ONS3010 and adalimumab (Humira ®). In order to quantify the effects innovative techniques will be applied including novel, circulating biomarkers, skin surface biomarkers via transdermal analysis patches, ex vivo biomarkers after stimulation of whole blood with LPS/Aluminium, three-dimensional photographs of target lesions and total body photography for a digital, computer-aided psoriasis severity assessment. |
|
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to participate in
the study:
1. Men or women at least 18 years of age at the time of screening
2. Chronic plaque-type psoriasis diagnosed for at least 6 months before
randomization and stable for at least 2 months before screening.
Patients will be considered to have stable disease if there have been no
new lesions while other lesions remain significantly the same, even if the
affected surface area is extensive.
3. Moderate to severe psoriasis as defined at screening and baseline by
meeting all of the following criteria:
o PASI score of 12 or greater
o sPGA score of 3 or greater (based on a scale of 0 to 5)
o BSA affected by plaque-type psoriasis of 10% or greater
4. Chronic plaque-type psoriasis patients who have previously received
phototherapy or systemic psoriasis therapy at least once or who are
candidates for such therapies in the opinion of the Investigator
5. Women of childbearing potential and all males must use an acceptable
form of birth control throughout the study. Women of childbearing
potential must agree to continue using birth control for 5 months after
the last dose. Acceptable methods of birth control include surgery
(bilateral tubal ligation, vasectomized partner), hormonal contraceptive
(oral, patch, injectable, implantable, intravaginal), intrauterine device,
or double physical barrier such as condom plus diaphragm. Postmenopausal status for >1 year will also satisfy this requirement. Also, males are not to donate sperm during the study or for 16 weeks after the last dose.
6. Ability and willingness to self-administer study drug
7. Ability to read and understand the informed consent form and provide written consent |
|
E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria are ineligible to participate in this study:
1. Forms of psoriasis other than chronic plaque-type
2. Drug-induced psoriasis
3. Ongoing use of prohibited psoriasis treatments. Washout periods prior to baseline (first dose of study drug) for prior psoriasis treatments are as follows:
o ≥2 weeks for topical medications and ultraviolet B (UVB) phototherapy
o ≥4 weeks for psoralen plus ultraviolet A (UVA) phototherapy
o ≥4 weeks for nonbiologic systemic therapies
o ≥12 weeks for other biologic therapies
o ≥12 months for alkylating agents
4. Exposure to live or live-attenuated vaccines within 8 weeks prior to the screening visit
5. Previous exposure to adalimumab
6. Treatment with an investigational agent within 12 weeks or 5 half-lives of the drug prior to screening, whichever is longer
7. Prior treatment with TNF inhibitors with lack of efficacy as per clinical judgment (primary failure)
8. Major surgery within 8 weeks prior to screening or planned to take place during the study period
9. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of study treatment
10. History of cancer or lymphoproliferative disease (other than successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix)
11. History of neurological symptoms suggestive of central nervous system demyelinating disease
12. Acute infection requiring treatment with parenteral antibiotics within 4 weeks prior to baseline (first dose of study drug) or oral/topical antibiotics within 2 weeks prior to baseline
13. History of human immunodeficiency virus 1 or 2, hepatitis B, or hepatitis C
14. Presence of chronic or acute infection at screening, including positive result for active TB or untreated latent TB (eg, positive QuantiFERON® test result without any prior history of active or latent TB, and without evidence of active infection), where the patient is not willing to undergo prophylactic treatment (see Section 11.3)
15. History of chronic infection or infections within the past 2 years requiring hospitalization or administration of intravenous antibiotics (without evidence of a cure)
16. Known hypersensitivity or history of anaphylactoid reaction(s) to adalimumab or its excipients
17. Presence of New York Heart Association (NYHA) Class III/IV heart failure (see Section 11.5)
18. History of congestive heart failure, recent cerebrovascular accident, or any other condition that, in the opinion of the Investigator, would put the patient at risk by participation in the study
19. History of clinically significant cardiac, respiratory (except for mild asthma), renal, hepatic, hematologic, gastrointestinal, neurologic, or psychiatric disease or disorder, or any other uncontrolled medical illness
20. Pregnant, a positive pregnancy test, or intending to become
pregnant during or within 5 months after completion of the study, or
breastfeeding
21. Impaired bone marrow or hepatic or renal function, including the
following:
o Hemoglobin <7.14 mmol/L (11.5 g/dL) for males or <6.21 mmol/L
(10.0 g/dL) for females, absolute neutrophil count <1.5 x 10^9/L (1500
cells/μL), platelets <100 x 10^9/L (100,000/μL)
o Total bilirubin ≥1.5 x ULN, excluding cases where elevated bilirubin
can be attributed to Gilbert's syndrome
o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
≥1.5 x ULN
o Creatinine ≥1.5 x ULN |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the PASI 75 response rate at Week 17. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy Endpoints
The secondary efficacy endpoints are as follows:
• PASI 75 and PASI 90 response rates over time
• PASI value and change in PASI from baseline at each visit
• Change from baseline in sPGA at each visit
• Percentage of patients with sPGA of 0 (clear) or 1 (almost clear) at
each visit
• Change from baseline in DLQI at each visit
Safety Endpoints
The safety endpoints of this study are as follows:
• Incidence of TEAEs and SAEs
• Incidence of adverse events (AEs) of special interest:
o Serious infections, including tuberculosis and other opportunistic
infections
o Malignancies
o Injection site reactions
o Hypersensitivity reactions including anaphylaxis
o Liver enzyme elevations
o Demyelinating diseases
o Lupus-like syndromes
o Heart failure
o Hematologic reactions
• Incidence of circulating ADAs
• Incidence of neutralizing antibodies
• Clinically significant changes in laboratory values |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PASI 75 and PASI 90 response rates over time
• PASI value and change in PASI from baseline at each visit
• Change from baseline in sPGA at each visit
• Percentage of patients with sPGA of 0 (clear) or 1 (almost clear) at each visit
• Change from baseline in DLQI at each visit
|
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Australia |
Bulgaria |
Canada |
Chile |
France |
Germany |
Hungary |
Mexico |
Netherlands |
New Zealand |
Poland |
Romania |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
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 | 3 |
E.8.9.1 | In the Member State concerned days | 7 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 7 |