Efficacy, Safety, and Immunogenicity of AVT04 With Moderate-to-Severe Chronic Plaque Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 3

Summary: 
      Safety and Efficacy study of AVT04 (Alvotech Biosimilar to Ustekinumab), in patients with
      moderate to severe plaque psoriasis
    

Detailed description: 
      AVT04 is a fully human immunoglobulin class G1κ monoclonal antibody that specifically binds
      to the shared p40 protein subunit of IL-12 and IL-23 and therefore inhibits their activites

      AVT04 is being developed to be a biosimilar with the European Union (EU)-licensed drug
      Stelara® (hereafter referred to as Stelara) ustekinumab, Anatomical Therapeutic Chemical
      code: L04AC05) injection for subcutaneous (SC) and intravenous use. Stelara is an anti-IL-12
      and anti-IL-23 monoclonal antibody approved for various indications. Indications approved in
      the EU11 and United States (US)12 include: PsO in adult and pediatric patients, psoriatic
      arthritis, Crohn's disease, and ulcerative colitis. Indications approved in the People's
      Republic of China include PsO and Crohn's disease.13 Approval status may differ in other
      geographic regions.

      This is a multicenter, double-blind, randomized, active control clinical study to compare the
      efficacy, safety, and immunogenicity of AVT04 versus Stelara in patients with moderate to
      severe chronic PsO.

      The active period of Study AVT04-GL-301 comprises 2 stages:

        -  Stage 1: Primary Efficacy Assessment (Day 1 to Week 15)

        -  Stage 2: Long Term Efficacy and Safety Assessment (Week 16 to 52) Stage 1 On Day 1,
           after successfully completing Screening activities, eligible patients will be randomized
           into Groups 1 and 2, in a 1:2 ratio (AVT04:Stelara), and begin Stage 1.

      Patient randomization will be stratified by presence or absence of previous biologic
      treatment, by region; ie, Europe or China, and by body weight category (≤80 kg vs >80 kg).

        -  Group 1: Patients will receive an initial dose of AVT04 45 mg administered SC, followed
           by 45 mg 4 weeks later.

        -  Group 2: Patients will receive an initial loading dose of Stelara, 45 mg administered
           SC, followed by 45 mg 4 weeks later.

      Stage 2

      At Week 16:

      Patients who were initially randomized in Group 1 (AVT04) will continue to receive AVT04 45
      mg SC every 12 weeks at Weeks 16, 28, and 40 (unless withdrawn from the study).

      Patients who were initially randomized in Group 2 (Stelara) will be re-randomized into Groups
      2A and 2B, in a 1:1 ratio:

        -  Group 2A: Patients will begin receiving AVT04 45 mg SC every 12 weeks, at Weeks 16, 28,
           and 40 (unless withdrawn from the study).

        -  Group 2B: Patients will continue to receive Stelara 45 mg SC every 12 weeks, at Weeks
           16, 28, and 40 (unless withdrawn from the study).

      At Week 28:

        -  Non-responsive patients (PASI improvement <50% compared to BL) will be encouraged to
           continue in the study for safety analyses, per the Schedule of Assessments (SoA) (Table
           7.1), but will not receive further study drug.

        -  Responsive patients (PASI improvement ≥50% compared to BL) will continue in the study.

      At Week 40: All patients who are still in the study (except Week 28 non-responsive patients)
      will receive the final study drug administration.

      At Week 52 (EoS/ET): All patients will undergo final efficacy and safety assessment.
    

Intervention name(s): Stelara; AVT04
Intervention type(s): Drug; Drug
Intervention description(s): AVT04 or Stelara (45 mg/5ml) will be administered as a subcutaneous injection in the thigh or abdomen per the approved dosing regimen for moderate to severe chronic PsO for patients with a body weight ≤100 kg.11,12; AVT04 or Stelara (45 mg/5ml) will be administered as a subcutaneous injection in the thigh or abdomen per the approved dosing regimen for moderate to severe chronic PsO for patients with a body weight ≤100 kg.11,12
Intervention MeSH terms: Ustekinumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment