| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 |
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| 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 |
Primary Objective:
• To compare the pharmacokinetics (PK) between patients receiving Humira® and patients undergoing repeated switches (Sw) between Humira and AVT02.
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| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• To descriptively compare efficacy between patients receiving Humira and patients undergoing repeated Sw between Humira and AVT02.
• To descriptively compare safety between patients receiving Humira and patients undergoing repeated Sw between Humira and AVT02.
• To descriptively compare the incidence of antibody presence between patients receiving Humira and patients undergoing repeated Sw between Humira and AVT02.
• The objective of the optional Extension Phase is to collect safety and immunogenicity data in patients with moderate to severe active plaque psoriasis treated with AVT02.
Exploratory Objective:
• To assess ex vivo immunogenicity in a subset of patients by T cell proliferation and cytokine production assay.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient has signed the informed consent form and documentation as required by relevant competent authorities and is able to understand and adhere to the visit schedule and study requirements.
2. Patient is male or female aged 18 to 75 years, inclusive, at the time of Screening.
3. Patients 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 Baseline (Week 1/Day 1).
4. Patient has had stable disease for at least 2 months (ie, without significant changes as defined by the Investigator or designee).
5. Patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.
6. Patient is naive to adalimumab therapy, approved or investigational.
7. 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:
a. No evidence of active TB on chest radiograph within 3 months prior to the first dose of study drug.
b. Documented history of treatment of TB or adequate prophylaxis initiation with an isoniazid-based regimen > 1 month prior to receiving study drug in accordance with local recommendations.
c. No known exposure to active TB after most recent prophylaxis.
d. Asymptomatic at Screening and Baseline.
Investigators should check with the medical monitor before enrolling such subjects.
8. 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 Baseline (Week 1/Day 1).
9. 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.
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| E.4 | Principal exclusion criteria |
Exclusion Criteria:
1. 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 treatment of psoriasis.
2. 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 Baseline (Week 1/Day 1).
b. PUVA phototherapy and/or UVB phototherapy within 4 weeks prior to the Baseline (Week 1/Day 1).
c. Nonbiologic psoriasis systemic therapies (eg, cyclosporine, methotrexate, and acitretin) within 4 weeks prior to the Baseline (Week 1/Day 1).
d. Any prior or concomitant adalimumab therapy, either approved or investigational.
e. Any systemic steroid in the 4 weeks prior to Screening.
f. Investigational agent(s) within 90 days or 5 half-lives (whichever is longer) before Baseline (Week 1/Day 1) (Refer to the table in protocol section 3.3.2 for approved/marketed products).
3. Patient has received live or attenuated vaccines during the 4 weeks prior to Screening or intends to receive a live or attenuated vaccine at any time during the study.
4. Patient has an 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 or designee, significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
5. Patient has a planned surgical intervention during the duration of the study and which, in the opinion of the Investigator or designee, will put the subject at further risk or hinder the patient’s ability to maintain compliance with study treatment and the visit schedule.
6. Has any active and serious infection or history of infections as follows:
a. Any active infection:
i. For which non-systemic anti-infective were used within 4 weeks prior to randomization. Note: patients receiving topical antibiotics for facial acne do not need to be excluded.
ii. 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 subject.
c. Invasive fungal infection or mycobacterial infection.
d. Opportunistic infections, such as listeriosis, legionellosis, or pneumocystis.
7. Patient is positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B surface antigen (HBsAg) and/or is positive for hepatitis B core antibody.
8. Patient has severe progressive or uncontrolled, clinically significant disease that in the judgment of the Investigator or designee renders the subject unsuitable for the study.
9. 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.
10. Patient has an active neurological disease, such as multiple sclerosis, Guillain-Barré syndrome, optic neuritis, and transverse myelitis, or a history of neurologic symptoms suggestive of central nervous system demyelinating disease.
11. Patient has moderate to severe heart failure (New York Heart Association [NYHA] Class III/IV).
12. Patient has a history of hypersensitivity to the active substance or to any of the excipients of Humira or AVT02.
13. Patient is pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation.
14. 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.
15. Is unable to follow study instructions and comply with the protocol in the opinion of the Investigator or designee.
16. Patient has a history of clinically significant hematological abnormalities, including cytopenias (eg, thrombocytopenia, leukopenia).
17. Has a laboratory abnormality that, in the opinion of the Investigator or designee, could cause this study to be detrimental to the subject. 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 and/or alanine aminotransferase that is persistently ≥ 2.5 × 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).
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint:
• Area under the concentration-time curve over the dosing interval from Week 26 to Week 28 (AUCtau, 26-28) and the maximum concentration over the dosing interval of from Week 26 to Week 28 (Cmax, 26-28).
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
Secondary Endpoints:
PK Endpoints
• Time to maximum concentration (Tmax) during the dosing interval from Week 26 to Week 28.
• Trough concentration (Ctrough) over the dosing interval from Week 26 to Week 28.
• Ctrough after each switch at Weeks 12, 16, and 20.
• Ratio of Ctrough after the last administration of study drug at Week 26 to Week 12.
• Ctrough after last administration of study drug at Week 26 in patients who are PASI75 responders and anti-drug antibody negative at Week 12.
Efficacy Endpoints
• Percent improvement in PASI from Week 1 to Week 28.
• Percent improvement in PASI from Week 12 to Week 28.
• Change in Dermatology Life Quality Index (DLQI) from Week 1 to Week 28.
• Change in DLQI from Week 12 to Week 28.
• Number and percentage of patients achieving sPGA responses of clear (0) or almost clear (1) at Weeks 12 and 28.
Safety Endpoints
• Incidence, type, and severity of adverse events (AEs) including adverse drug reactions (ADR).
• Incidence and severity of injection site reactions (ISR).
Immunogenicity Endpoints
• Comparison of antidrug antibodies in Group 1 (AVT02/Humira/AVT02) and Group 2 (Humira only) in the Switching Module at Baseline, Weeks 12, 16, 20, 26, and 28.
Exploratory Endpoint:
Ex vivo immunogenicity by T-cell proliferation and cytokine production will be assessed in a subset of patients at Weeks 1 (Baseline), 12, 16 and 28.
Extension Phase Endpoints:
• Incidence, type, and severity of AEs including ADR.
• Incidence and severity of ISR.
• Detection of antidrug antibodies to AVT02 at Weeks 42 and 52.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK Endpoints: weeks 12-28.
Efficacy Endpoints: weeks 1-28.
Safety Endpoints: throughout the study.
Immunogenicity Endpoints: weeks 1, 12, 16, 20, 26 and 28.
Exploratory Endpoints: weeks 1, 12, 16, 28.
Extention phase Endpoints: trough Weeks 28-52. |
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| 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 | 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
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| 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 |
| LeadInPeriod: W1-12–Open Label; Switching Module: W12-28–Double Blind; Extension: W28-52-Open-Label |
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| 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 | Yes |
| E.8.2.3.1 | Comparator description |
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| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 |
| Georgia |
| Russian Federation |
| Ukraine |
| Iceland |
| Poland |
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| 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
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| The EoS visit is planned for Week 52 (ie, 2 weeks after the final study drug administration at Week 50). |
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| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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