<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04453137</url>
  </required_header>
  <id_info>
    <org_study_id>AVT02-GL-302</org_study_id>
    <nct_id>NCT04453137</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic, Efficacy, Safety, and Immunogenicity of AVT02 With Moderate to Severe Chronic Plaque Psoriasis</brief_title>
  <official_title>Multicenter, Double-Blind, Randomized, Parallel-group, Study Evaluating PK, Efficacy, Safety, and Immunogenicity in Patients With Plaque Psoriasis Receiving Humira® or AVT02 Followed by a Safety Extension Phase of AVT02</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alvotech Swiss AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alvotech Swiss AG</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pharmacokinetic, Efficacy, Safety, and Immunogenicity Between Patients with Moderate to&#xD;
      Severe Chronic Plaque Psoriasis Receiving Humira® and Patients with Moderate to Severe&#xD;
      Chronic Plaque Psoriasis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized, double-blind, parallel-group study to evaluate PK,&#xD;
      efficacy, safety, and immunogenicity between patients with moderate to severe chronic plaque&#xD;
      psoriasis receiving Humira and patients with moderate to severe chronic plaque psoriasis&#xD;
      undergoing repeated switches between Humira and AVT02, followed by an optional safety&#xD;
      Extension Phase.&#xD;
&#xD;
      AVT02-GL-302 study is composed of 3 parts:&#xD;
&#xD;
      LeadIn Period: Week 1-12 - OpenLabel Treatment Switching Module: Week 12-28 - DoubleBlind&#xD;
      Treatment Optional Extension Phase: Week 28-52 - OpenLabel Treatment&#xD;
&#xD;
      Lead-In Period:&#xD;
&#xD;
      After successfully completing Screening activities, patients will be enrolled in the LeadIn&#xD;
      Period.&#xD;
&#xD;
      During the LeadIn Period, patients will receive Humira (initial dose of 80 mg [2 × 40 mg]&#xD;
      administered subcutaneously [SC], followed by 40 mg SC given every other week starting 1 week&#xD;
      after the initial dose). At Week 12, responsive patients (Psoriasis Area and Severity Index&#xD;
      [PASI] ≥ 75 [PASI75]) will be randomly assigned in a 1:1 ratio to either of the following&#xD;
      groups for participation in the Double-Blind Switching Module.&#xD;
&#xD;
      Switching Module:&#xD;
&#xD;
      Group 1: patients undergo repeated switches (Sw) of AVT02 and Humira from Week 12 until Week&#xD;
      26:&#xD;
&#xD;
      Sw1-AVT02 (40 mg every other week) for 4 weeks (2 injections), Sw2-Humira (40 mg every other&#xD;
      week) for 4 weeks (2 injections), Sw3-AVT02 (40 mg every other week) for 8 weeks (4&#xD;
      injections). Group 2: patients continue to receive Humira 40 mg every other week from Week 12&#xD;
      until Week 26 (8 injections) The last study treatment administration in the Double-Blind&#xD;
      Switching Module is at Week 26. The last study assessment is at Week 28 for both groups. The&#xD;
      end-of-study (EoS) visit for the interchangeability (IC) part of study is planned at Week 28&#xD;
      (ie, 2 weeks after the last study treatment administration, EoS IC).&#xD;
&#xD;
      Extension Phase:&#xD;
&#xD;
      At Week 28, after the EoS IC visit, responsive patients (PASI ≥ 50 [PASI50]) will be offered&#xD;
      to continue with the optional open-label Extension Phase (Weeks 28 to 52). AVT02 40 mg will&#xD;
      be administered every other week starting from Week 28 (after completing EoS IC assessments),&#xD;
      ending with the final study drug administration at Week 50. The EoS visit is planned for Week&#xD;
      52.&#xD;
&#xD;
      The clinical study report (CSR) for the IC part of the study will include the data from the&#xD;
      OpenLabel Lead-In Period and Double-Blind Switching Module.&#xD;
&#xD;
      The Extension Phase CSR will include the data from the additional 24-week Open-Label&#xD;
      Extension Phase (Weeks 28 to 52).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Actual">November 16, 2021</completion_date>
  <primary_completion_date type="Actual">May 31, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Open label lead-in phase, followed by blinded 1:1 randomization with open label extension phase.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve over the dosing interval from Week 26 to Week 28 (AUCtau,26-28)</measure>
    <time_frame>Week 26 to Week 28</time_frame>
    <description>Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUCtau, 26-28) of AVT02 and Humira</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum concentration over the dosing interval from Week 26 to Week 28 (Cmax, 26-28)</measure>
    <time_frame>Week 26 to Week 28</time_frame>
    <description>Venous blood samples will be collected for measurement of serum concentration of AVT02 and Humira</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Psoriasis Area and severity index</measure>
    <time_frame>Week 1 to Week 28 and week 12 to Week 28</time_frame>
    <description>Percent (%) improvement of PASI from Week 1 to Week 28 and from Week 12 to Week 28</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">567</enrollment>
  <condition>Plaque Psoriasis</condition>
  <arm_group>
    <arm_group_label>Humira 40 mg/mL (Adalimumab Originator)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>During the LeadIn Period, patients will receive Humira (initial dose of 80 mg [2 × 40 mg] administered subcutaneously [SC], followed by 40 mg SC given every other week starting 1 week after the initial dose). At Week 12, responsive patients (Psoriasis Area and Severity Index [PASI] ≥ 75 [PASI75]) will be randomly assigned in a 1:1 ratio to either of the following groups for participation in the Double-Blind Switching Module.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IC - Humira 40 mg/mL (Adalimumab Originator)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients continue to receive Humira 40 mg every other week from Week 12 until Week 26 (8 injections)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients undergo repeated switches (Sw) of AVT02 and Humira from Week 12 until Week 26:&#xD;
Sw1-AVT02 (40 mg every other week) for 4 weeks (2 injections),&#xD;
Sw2-Humira (40 mg every other week) for 4 weeks (2 injections),&#xD;
Sw3-AVT02 (40 mg every other week) for 8 weeks (4 injections).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVT02 40 mg/mL (Adalimimab Biosimilar)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At Week 28, after the EoS IC visit, responsive patients (PASI ≥ 50 [PASI50]) will be offered to continue with the optional open-label Extension Phase (Weeks 28 to 52). AVT02 40 mg will be administered every other week starting from Week 28 (after completing EoS IC assessments), ending with the final study drug administration at Week 50. The EoS visit is planned for Week 52.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab originator</intervention_name>
    <description>Subcutaneous injection every other week</description>
    <arm_group_label>Humira 40 mg/mL (Adalimumab Originator)</arm_group_label>
    <arm_group_label>IC - Humira 40 mg/mL (Adalimumab Originator)</arm_group_label>
    <arm_group_label>IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab biosimilar</intervention_name>
    <description>Subcutaneous injection every other week</description>
    <arm_group_label>AVT02 40 mg/mL (Adalimimab Biosimilar)</arm_group_label>
    <arm_group_label>IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)</arm_group_label>
    <other_name>AVT02</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient has signed the informed consent form and documentation as required by relevant&#xD;
             competent authorities and is able to understand and adhere to the visit schedule and&#xD;
             study requirements.&#xD;
&#xD;
          2. Patient is male or female aged 18 to 75 years, inclusive, at the time of Screening.&#xD;
&#xD;
          3. Patients with moderate-to-severe chronic plaque psoriasis who has involved body&#xD;
             surface area (BSA) ≥ 10% (Palm Method), ≥ 12 on the PASI, and static Physicians Global&#xD;
             Assessments (sPGA) ≥ 3 (moderate) at Screening and at Baseline (Week 1/Day 1).&#xD;
&#xD;
          4. Patient has had stable disease for at least 2 months (ie, without significant changes&#xD;
             as defined by the Investigator or designee).&#xD;
&#xD;
          5. Patients with moderate to severe chronic plaque psoriasis who are candidates for&#xD;
             systemic therapy or phototherapy, and when other systemic therapies are medically less&#xD;
             appropriate.&#xD;
&#xD;
          6. Patient is naive to adalimumab therapy, approved or investigational.&#xD;
&#xD;
          7. Patient has a negative QuantiFERON test for tuberculosis (TB) during Screening. Note:&#xD;
             Patients with an indeterminate QuantiFERON test are allowed if they have all of the&#xD;
             following:&#xD;
&#xD;
               1. No evidence of active TB on chest radiograph within 3 months prior to the first&#xD;
                  dose of study drug.&#xD;
&#xD;
               2. Documented history of treatment of TB or adequate prophylaxis initiation with an&#xD;
                  isoniazid-based regimen &gt; 1 month prior to receiving study drug in accordance&#xD;
                  with local recommendations.&#xD;
&#xD;
               3. No known exposure to active TB after most recent prophylaxis.&#xD;
&#xD;
               4. Asymptomatic at Screening and Baseline. Investigators should check with the&#xD;
                  medical monitor before enrolling such subjects.&#xD;
&#xD;
          8. Women of childbearing potential (except those who are postmenopausal for more than 2&#xD;
             years or if surgically sterile) must have a negative serum pregnancy test during&#xD;
             Screening and negative urine pregnancy test at Baseline (Week 1/Day 1).&#xD;
&#xD;
          9. Sexually active women of childbearing potential must agree to use highly effective&#xD;
             contraception (sterilization, hormonal contraception pills or injection or implants,&#xD;
             sterilization and abstinence) for the duration of the study and until 6 months after&#xD;
             the last dose of the study drug. Male patients must agree to use contraception for the&#xD;
             duration of the study and agree not to donate sperm during and for 6 months after the&#xD;
             last dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis,&#xD;
             medication-induced psoriasis, other skin conditions (eg, eczema), or other systemic&#xD;
             autoimmune disorder inflammatory disease at the time of the Screening visit that would&#xD;
             interfere with evaluations of the effect of the study treatment of psoriasis.&#xD;
&#xD;
          2. Patient has prior use of any of the following medications within specified time&#xD;
             periods or will require use during the study:&#xD;
&#xD;
               1. Topical medications within 2 weeks of Baseline (Week 1/Day 1). PUVA phototherapy&#xD;
                  and/or UVB phototherapy within 4 weeks prior to the Baseline (Week 1/Day 1).&#xD;
&#xD;
               2. Nonbiologic psoriasis systemic therapies (eg, cyclosporine, methotrexate, and&#xD;
                  acitretin) within 4 weeks prior to the Baseline (Week 1/Day 1).&#xD;
&#xD;
               3. Any prior or concomitant adalimumab therapy, either approved or investigational.&#xD;
&#xD;
               4. Any systemic steroid in the 4 weeks prior to Screening.&#xD;
&#xD;
               5. Investigational agent(s) within 90 days or 5 half-lives (whichever is longer)&#xD;
                  before Baseline (Week 1/Day 1) (Refer to the following table for&#xD;
                  approved/marketed products).&#xD;
&#xD;
             Specified washout periods are as follows:&#xD;
&#xD;
               -  Adalimumab: not allowed&#xD;
&#xD;
               -  Alefacept, Briakinumab, Brodalumab, Golimumab: 24 weeks&#xD;
&#xD;
               -  Ustekinumab: 15 weeks&#xD;
&#xD;
               -  Etanercept , Secukinumab , Infliximab , Certolizumab, Pegol: 12 weeks&#xD;
&#xD;
               -  Cyclosporine: 4 weeks&#xD;
&#xD;
               -  Methotrexate: 4 weeks&#xD;
&#xD;
               -  PUVA-UVA/UVB: 4 weeks&#xD;
&#xD;
               -  Oral retinoid: 4 weeks&#xD;
&#xD;
               -  Corticosteroids IM - IV - oral - intra-articular for psoriatic arthritis: 4 weeks&#xD;
&#xD;
               -  Topical psoriasis treatments (except in face, eyes, scalp, palms, soles, and&#xD;
                  genital area and except only mild potency steroids in these areas): 2 weeks&#xD;
&#xD;
          3. Patient has received live or attenuated vaccines during the 4 weeks prior to Screening&#xD;
             or intends to receive a live or attenuated vaccine at any time during the study.&#xD;
&#xD;
          4. Patient has an underlying condition (including, but not limited to, metabolic,&#xD;
             hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or&#xD;
             gastrointestinal) which, in the opinion of the Investigator or designee, significantly&#xD;
             immunocompromises the subject and/or places the subject at unacceptable risk for&#xD;
             receiving an immunomodulatory therapy.&#xD;
&#xD;
          5. Patient has a planned surgical intervention during the duration of the study and&#xD;
             which, in the opinion of the Investigator or designee, will put the subject at further&#xD;
             risk or hinder the patient's ability to maintain compliance with study treatment and&#xD;
             the visit schedule.&#xD;
&#xD;
          6. Has any active and serious infection or history of infections as follows:&#xD;
&#xD;
               1. Any active infection:&#xD;
&#xD;
                    -  For which non-systemic anti-infective were used within 4 weeks prior to&#xD;
                       randomization. Note: patients receiving topical antibiotics for facial acne&#xD;
                       do not need to be excluded.&#xD;
&#xD;
                    -  Which required hospitalization or systemic anti-infective within 8 weeks&#xD;
                       prior to randomization.&#xD;
&#xD;
               2. Recurrent or chronic infections or other active infection that, in the opinion of&#xD;
                  the Investigator or designee, might cause this study to be detrimental to the&#xD;
                  subject.&#xD;
&#xD;
               3. Invasive fungal infection or mycobacterial infection.&#xD;
&#xD;
               4. Opportunistic infections, such as listeriosis, legionellosis, or pneumocystis.&#xD;
&#xD;
          7. Patient is positive for human immunodeficiency virus, hepatitis C virus antibody, or&#xD;
             hepatitis B surface antigen (HBsAg) and/or is positive for hepatitis B core antibody.&#xD;
&#xD;
          8. Patient has severe progressive or uncontrolled, clinically significant disease that in&#xD;
             the judgment of the Investigator or designee renders the subject unsuitable for the&#xD;
             study.&#xD;
&#xD;
          9. Patient has a history of malignancy within 5 years except for adequately treated&#xD;
             cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast&#xD;
             ductal carcinoma.&#xD;
&#xD;
         10. Patient has an active neurological disease, such as multiple sclerosis, Guillain-Barré&#xD;
             syndrome, optic neuritis, and transverse myelitis, or a history of neurologic symptoms&#xD;
             suggestive of central nervous system demyelinating disease.&#xD;
&#xD;
         11. Patient has moderate to severe heart failure (New York Heart Association [NYHA] Class&#xD;
             III/IV).&#xD;
&#xD;
         12. Patient has a history of hypersensitivity to the active substance or to any of the&#xD;
             excipients of Humira or AVT02.&#xD;
&#xD;
         13. Patient is pregnant or nursing (lactating) woman, where pregnancy is defined as the&#xD;
             state of a female after conception and until the termination of gestation.&#xD;
&#xD;
         14. Patient exhibits evidence (as assessed by the Investigator or designee using good&#xD;
             clinical judgment) of active substance abuse (alcohol or drugs) within 6 months of&#xD;
             Screening that may impact patient's ability to participate in the study.&#xD;
&#xD;
         15. Is unable to follow study instructions and comply with the protocol in the opinion of&#xD;
             the Investigator or designee.&#xD;
&#xD;
         16. Patient has a history of clinically significant hematological abnormalities, including&#xD;
             cytopenias (eg, thrombocytopenia, leukopenia).&#xD;
&#xD;
         17. Has a laboratory abnormality that, in the opinion of the Investigator or designee,&#xD;
             could cause this study to be detrimental to the subject. The following laboratory&#xD;
             abnormalities should be carefully considered:&#xD;
&#xD;
               1. Hemoglobin &lt; 9 g/dL.&#xD;
&#xD;
               2. Platelet count &lt; 100,000/mm3.&#xD;
&#xD;
               3. White blood cell count &lt; 3000 cells/mm3.&#xD;
&#xD;
               4. Aspartate aminotransferase and/or alanine aminotransferase that is persistently ≥&#xD;
                  2.5 × the upper limit of normal. (Persistently indicates at least on 2 occasions&#xD;
                  separated by a number of days).&#xD;
&#xD;
               5. Creatinine clearance &lt; 50 mL/min (Cockcroft-Gault formula).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Feldman, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>9901</name>
      <address>
        <city>Tbilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - 9904</name>
      <address>
        <city>Tbilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 9902</name>
      <address>
        <city>Tbilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 9903</name>
      <address>
        <city>Tbilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3501</name>
      <address>
        <city>Reykjavik</city>
        <country>Iceland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 4803</name>
      <address>
        <city>Gdańsk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 4804</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 4807</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 4806</name>
      <address>
        <city>Toruń</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wromedica Centrum Zdrowia</name>
      <address>
        <city>Wrocław</city>
        <zip>51-685</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - 4808</name>
      <address>
        <city>Wrocław</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 4805</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7001</name>
      <address>
        <city>Kemerovo</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7005</name>
      <address>
        <city>Krasnodar</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7003</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7004</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7006</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 7002</name>
      <address>
        <city>Saratov</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3805</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3807</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3801</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3806</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss Ag - Site 3802</name>
      <address>
        <city>Rivne</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3804</name>
      <address>
        <city>Uzhgorod</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alvotech Swiss AG - Site 3803</name>
      <address>
        <city>Zaporizhzhya</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Georgia</country>
    <country>Iceland</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04453137
org study id: AVT02-GL-302
nct id: NCT04453137
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pharmacokinetic, Efficacy, Safety, and Immunogenicity Between Patients with Moderate to
      Severe Chronic Plaque Psoriasis Receiving Humira® and Patients with Moderate to Severe
      Chronic Plaque Psoriasis
This is a multicenter, randomized, double-blind, parallel-group study to evaluate PK,
      efficacy, safety, and immunogenicity between patients with moderate to severe chronic plaque
      psoriasis receiving Humira and patients with moderate to severe chronic plaque psoriasis
      undergoing repeated switches between Humira and AVT02, followed by an optional safety
      Extension Phase.

      AVT02-GL-302 study is composed of 3 parts:

      LeadIn Period: Week 1-12 - OpenLabel Treatment Switching Module: Week 12-28 - DoubleBlind
      Treatment Optional Extension Phase: Week 28-52 - OpenLabel Treatment

      Lead-In Period:

      After successfully completing Screening activities, patients will be enrolled in the LeadIn
      Period.

      During the LeadIn Period, patients will receive Humira (initial dose of 80 mg [2 × 40 mg]
      administered subcutaneously [SC], followed by 40 mg SC given every other week starting 1 week
      after the initial dose). At Week 12, responsive patients (Psoriasis Area and Severity Index
      [PASI] ≥ 75 [PASI75]) will be randomly assigned in a 1:1 ratio to either of the following
      groups for participation in the Double-Blind Switching Module.

      Switching Module:

      Group 1: patients undergo repeated switches (Sw) of AVT02 and Humira from Week 12 until Week
      26:

      Sw1-AVT02 (40 mg every other week) for 4 weeks (2 injections), Sw2-Humira (40 mg every other
      week) for 4 weeks (2 injections), Sw3-AVT02 (40 mg every other week) for 8 weeks (4
      injections). Group 2: patients continue to receive Humira 40 mg every other week from Week 12
      until Week 26 (8 injections) The last study treatment administration in the Double-Blind
      Switching Module is at Week 26. The last study assessment is at Week 28 for both groups. The
      end-of-study (EoS) visit for the interchangeability (IC) part of study is planned at Week 28
      (ie, 2 weeks after the last study treatment administration, EoS IC).

      Extension Phase:

      At Week 28, after the EoS IC visit, responsive patients (PASI ≥ 50 [PASI50]) will be offered
      to continue with the optional open-label Extension Phase (Weeks 28 to 52). AVT02 40 mg will
      be administered every other week starting from Week 28 (after completing EoS IC assessments),
      ending with the final study drug administration at Week 50. The EoS visit is planned for Week
      52.

      The clinical study report (CSR) for the IC part of the study will include the data from the
      OpenLabel Lead-In Period and Double-Blind Switching Module.

      The Extension Phase CSR will include the data from the additional 24-week Open-Label
      Extension Phase (Weeks 28 to 52).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open label lead-in phase, followed by blinded 1:1 randomization with open label extension phase.
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Area under the concentration-time curve over the dosing interval from Week 26 to Week 28 (AUCtau,26-28)
time frame: Week 26 to Week 28
description: Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUCtau, 26-28) of AVT02 and Humira
measure: Maximum concentration over the dosing interval from Week 26 to Week 28 (Cmax, 26-28)
time frame: Week 26 to Week 28
description: Venous blood samples will be collected for measurement of serum concentration of AVT02 and Humira
measure: Psoriasis Area and severity index
time frame: Week 1 to Week 28 and week 12 to Week 28
description: Percent (%) improvement of PASI from Week 1 to Week 28 and from Week 12 to Week 28
arm group label: Humira 40 mg/mL (Adalimumab Originator)
arm group type: Active Comparator
description: During the LeadIn Period, patients will receive Humira (initial dose of 80 mg [2 × 40 mg] administered subcutaneously [SC], followed by 40 mg SC given every other week starting 1 week after the initial dose). At Week 12, responsive patients (Psoriasis Area and Severity Index [PASI] ≥ 75 [PASI75]) will be randomly assigned in a 1:1 ratio to either of the following groups for participation in the Double-Blind Switching Module.
arm group label: IC - Humira 40 mg/mL (Adalimumab Originator)
arm group type: Active Comparator
description: patients continue to receive Humira 40 mg every other week from Week 12 until Week 26 (8 injections)
arm group label: IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)
arm group type: Experimental
description: patients undergo repeated switches (Sw) of AVT02 and Humira from Week 12 until Week 26:
Sw1-AVT02 (40 mg every other week) for 4 weeks (2 injections),
Sw2-Humira (40 mg every other week) for 4 weeks (2 injections),
Sw3-AVT02 (40 mg every other week) for 8 weeks (4 injections).
arm group label: AVT02 40 mg/mL (Adalimimab Biosimilar)
arm group type: Experimental
description: At Week 28, after the EoS IC visit, responsive patients (PASI ≥ 50 [PASI50]) will be offered to continue with the optional open-label Extension Phase (Weeks 28 to 52). AVT02 40 mg will be administered every other week starting from Week 28 (after completing EoS IC assessments), ending with the final study drug administration at Week 50. The EoS visit is planned for Week 52.
intervention type: Biological
intervention name: Adalimumab originator
description: Subcutaneous injection every other week
arm group label: Humira 40 mg/mL (Adalimumab Originator)
arm group label: IC - Humira 40 mg/mL (Adalimumab Originator)
arm group label: IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)
other name: Humira
intervention type: Biological
intervention name: Adalimumab biosimilar
description: Subcutaneous injection every other week
arm group label: AVT02 40 mg/mL (Adalimimab Biosimilar)
arm group label: IC - Humira/AVT02 40 mg/mL (Adalimimab Biosimilar)
other name: AVT02
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Steven Feldman, MD, PhD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
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country: Georgia
country: Iceland
country: Poland
country: Russian Federation
country: Ukraine
responsible party type: Sponsor
mesh term: Psoriasis
mesh term: Adalimumab
sharing ipd: No