| 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 |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| 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 assess the equivalence by Psoriasis Area and Severity Index (PASI) of AVT02 to EU-approved Humira with regards to efficacy at Week 16 in patients with moderate-to-severe chronic plaque psoriasis |
|
| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• To compare the efficacy of AVT02 and EU-approved Humira in patients with moderate-to-severe chronic plaque psoriasis at Visits 8, 12, 16, 24, 32, 42, and 50
• To compare steady-state pharmacokinetics of AVT02 and EU approved Humira
• To compare the safety, tolerability, and immunogenicity of AVT02 and EU-approved Humira at Weeks 16, 24, 32, 42, and 50
Exploratory Objectives:
• To compare the efficacy of AVT02 and EU-approved Humira in patients with psoriatic arthritis (PsA) at Week 12
• Change from Baseline (BL) in Routine Assessment of Patient Index Data 3 (RAPID3) at Week 12 (only for PsA)
• To assess ex-vivo immunogenicity by T-cell proliferation and cytokine production in a subset of patients at Weeks 1, 8, and 16
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Patient has signed the Informed Consent Form (ICF) and is able to understand and adhere to the visit schedule and study requirements.
2.Patient is male or female, 18 to 75 years of age, inclusive, at time of Screening.
3.Patient with moderate-to-severe chronic plaque psoriasis who has involved body surface area (BSA) ≥ 10% (Palm Method), ≥ 12 on the PASI, and static Physicians Global Assessments (sPGA) ≥ 3 (moderate) at Screening and at BL.
4.Patient has had stable psoriatic disease for at least 2 months (ie, without significant changes as defined by the Investigator or designee).
5.Patient is a candidate for systemic therapy and the patient has a previous failure, inadequate response, intolerance, or contraindication to at least 1 systemic antipsoriatic therapy including, but not limited to, methotrexate, cyclosporine, psoralen plus ultraviolet light A (PUVA), and ultraviolet light B (UVB).
6.Patient has a negative QuantiFERON test for tuberculosis (TB) during Screening.
Note: Patients with an indeterminate QuantiFERON test are allowed if they have all of the following:
•No evidence of active TB on chest radiograph within 3 months prior to the first dose of study drug.
•Documented history of adequate prophylaxis initiation prior to receiving study drug in accordance with local recommendations.
•No known exposure to active TB after most recent prophylaxis.
•Asymptomatic at Screening and BL.
Investigators should check with the medical monitor before enrolling such subjects.
7.Women of childbearing potential (except those who are postmenopausal for more than 2 years or if surgically sterile) must have a negative serum pregnancy test during Screening and negative urine pregnancy test at BL.
Sexually active women of childbearing potential must agree to use highly effective contraception (sterilization, hormonal contraception pills or injection or implants, sterilization and abstinence) for the duration of the study and until 6 months after the last dose of the study drug.
Male patients must agree to use contraception for the duration of the study and agree not to donate sperm during and for 6 months after the last dose of study drug.
|
|
| E.4 | Principal exclusion criteria |
1.Patient has prior use of 2 or more biologics for treatment of PsO
2.Patient diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, other skin conditions (eg, 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 drug on psoriasis
3.Patient has prior use of any of the following medications within specified time periods or will require use during the study:
a)Topical medications within 2 weeks of BL (Week 1)
b)PUVA phototherapy and/or UVB phototherapy within 4 weeks prior to the BL Visit
c)Nonbiologic psoriasis systemic therapies (eg, cyclosporine, methotrexate, and acitretin) within 4 weeks prior to the BL Visit
d)Any prior or concomitant or biosimilar adalimumab therapy, either approved or investigational
e)Any systemic steroid in the 4 weeks prior to BL. Specified washout periods are as follows:
1.Investigational agent(s) within 90 days or 5 half-lives (whichever is longer) before BL (Week 1) (Refer to Table 1 for approved/marketed products)
4.Patient has received live or attenuated vaccines during the 4 weeks prior to Randomization or has the intention of receiving a live or attenuated vaccine at any time during the study. Patients who test positive for TB must be treated for 1 month prior to taking part in the study. Investigators should check with the medical monitor before enrolling patients receiving active treatment for TB
5.Patient has any concurrent condition which, in the opinion of the Investigator, significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy
6.Patient 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 patient at further risk or hinder the patient’s ability to maintain compliance with study drug and the visit schedule
7.Patient has an active and serious infection or history of infections as follows:
a)Any active infection
1)For which nonsystemic anti-infectives were used within 4 weeks prior to Randomization. Note: Patients receiving topical antibiotics for facial acne do not need to be excluded
2)Which required hospitalization or systemic anti-infective within 8 weeks prior to Randomization
b)Recurrent or chronic infections or other active infection that, in the opinion of the Investigator or designee, might cause this study to be detrimental to the patient
c)Invasive fungal infection or mycobacterial infection
d)Opportunistic infections, such as listeriosis, legionellosis, or pneumocystis.
8.Patient is positive for human immunodeficiency virus, hepatitis C virus antibody, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
9.Patient has severe progressive or uncontrolled, clinically significant disease that in the judgment of the Investigator renders the patient unsuitable for the study
10.Patient has a history of malignancy within 5 years except for adequately treated cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma
11.Patient 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
12.Patient has moderate-to-severe heart failure (New York Heart Association [NYHA] class III/IV)
13.Patient has a known history of allergic reactions attributed to compounds of similar chemical or biologic composition to active substance or to any of the excipients of Humira or AVT02
14.Patient is a pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation
15.Patient exhibits evidence (as assessed by the Investigator or designee using good clinical judgment) of active substance abuse (alcohol or drugs) within 6 months of Screening that may impact patient’s ability to participate in the study
16.Patient has clinically significant hematological abnormalities, including cytopenias (eg, thrombocytopenia, leukopenia) within 3 months prior to Screening
17.Patient has a laboratory abnormality that, in the opinion of the Investigator or designee, could cause this study to be detrimental to the patient. The following laboratory abnormalities should be carefully considered:
a)Hemoglobin < 9 g/dL
b)Platelet count < 100,000/mm3
c)White blood cell count < 3000 cells/mm3
d)Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) that is persistently ≥ 2 × the upper limit of normal. (Persistently indicates at least on 2 occasions separated by a number of days)
e)Creatinine clearance < 50 mL/min (Cockcroft-Gault formula)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| •Percent improvement in Psoriasis Area and Severity Index (PASI) from BL to Week 16 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Percent improvement in PASI from BL to Week 8, 12, 24, 32, 42, and 50
•PASI 50, PASI 75, PASI 90, and PASI 100 response rate at Weeks 16, 24, and 50
•Number and percentage of patients achieving sPGA responses of clear (0) or almost clear (1) at Weeks 16, 24, and 50
•Change from BL in quality of life as measured by Dermatology Life Quality Index (DLQI) scores at Weeks 16, 24, and 50
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 |
| Immunogenicity, Tolerability |
|
| 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 | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| 2 stages: 1-15 weeks, 16-50 weeks. |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
| Estonia |
| Georgia |
| Poland |
| Russian Federation |
| Ukraine |
|
| 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
|
| The end-of-study visit at Week 54 (ie, 6 weeks after receiving the final dose of study drug). |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
