Efficacy, Safety, and Immunogenicity of AVT04 With Moderate-to-Severe Chronic Plaque Psoriasis

NCT04930042 | Completed Phase 3

• 1 other identifier: AVT04-GL-301
• Study Type: interventional
• Target: 581
• Locations: 4 countries
• Sites: 30

Brief Summary

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

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (1)

• Psoriasis Area and Severity Index (PASI)

  Percent (%) change in Psoriasis Area and Severity Index (PASI)

  Baseline to week 12

Secondary Outcomes (2)

• PASI 50, 75, 90 and 100 response rates

  Baseline to week 52

• PASI percent improvement

  Baseline to week 52

Study Arms (2)

AVT04 45 mg SC

EXPERIMENTAL

Test Product: AVT04 (ustekinumab) Initial loading dose of 45 mg followed by 45 mg SC once every 12 weeks starting 4 weeks after the initial loading dose administered SC. Injected as subcutaneous in thigh and abdomen.

Drug: AVT04

EU Stelara 45 mg SC

ACTIVE COMPARATOR

Comparator ref product: EU Stelara (ustekinumab) Initial loading dose of 45 mg followed by 45 mg SC once every 12 weeks starting 4 weeks after the initial loading dose administered SC. Injected as subcutaneous in thigh and abdomen.

Drug: Stelara

Interventions

Stelara DRUG

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

EU Stelara 45 mg SC

AVT04 DRUG

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 45 mg SC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has signed the informed consent form (ICF) and documentation as required by relevant competent authorities and is able to understand and adhere to the visit schedule and study requirements.
• Chinese patients shall be recruited in Mainland China.
• Patient is male or female, aged 18 to 75 years old, inclusive, at time of Screening.
• Patient weighs ≤100 kg at Screening and at BL.
• Patient has had moderate to severe chronic PsO for at least 6 months.
• Patient has involved body surface area (BSA) ≥10%, PASI ≥12, and sPGA ≥3 (moderate) at Screening and at BL.
• Patient has had stable psoriatic disease for at least 2 months (ie, without significant changes as defined by the investigator or designee) prior to Screening.
• Patient is a candidate for systemic therapy because the patient has had 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).
• 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 patients.
• Patient is naïve to ustekinumab therapy, approved or investigational.

You may not qualify if:

• Patient diagnosed with psoriatic arthritis, 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.
• Patient has prior use of any of the following medications within specified time periods or will require use during the study:
• Topical medications within 2 weeks of BL visit (except low- to mid-potency topical corticosteroids on face, eyes, scalp, palms, soles, and genital area; only).
• PUVA phototherapy and/or UVB phototherapy within 4 weeks prior to the BL visit.
• Nonbiologic psoriasis systemic therapies (eg, cyclosporine, methotrexate, and acitretin) within 4 weeks prior to the BL visit.
• Any systemic steroid in the 4 weeks prior to the BL visit.
• Any oral traditional Chinese medicine (TCM) 4 weeks prior to the BL visit or any topical TCM 2 weeks prior to the BL visit.
• Investigational agent(s) within 90 days or 5 half-lives (whichever is longer) before BL visit.
• Other systemic biologics within 90 days or 5 half-lives (whichever is the longer) before BL visit.
• Any therapeutic agent targeting IL-12, IL-17 or IL-23 at any time. Specified washout periods for approved/marketed products are provided in Table 5.1.
• Table 5.1: Approved/Marketed Products Medication or Therapy Washout before BL Biologic Therapies, including but limited to: Adalimumab Etanercept Secukinumab Infliximab Certolizumab pegol Alefacept Briakinumab Guselkumab Brodalumab 12 weeks 8 weeks 12 weeks 12 weeks 24 weeks 24 weeks 24 weeks 13 weeks 13 weeks Any kinase inhibitor for any reason (eg, tofacitinib citrate) 1 day Any phosphodiesterase type 4 inhibitor (eg, apremilast \[Otezla\]) 4 weeks Cyclosporine 4 weeks Methotrexate 4 weeks PUVA-UVA/UVB 4 weeks Topical psoriasis treatments (examples include vitamin D analogs, topical steroids, polifenols, etc) (except low- to mid-potency topical corticosteroids on face, eyes, scalp, palms, soles, and genital area; only) 2 weeks Oral retinoids 4 weeks Corticosteroids IM - IV - oral - intraarticular 4 weeks Drugs that may cause new onset or exacerbation of psoriasis (including, but not limited to, beta blockers, lithium, and anti-malarials) 6 months1 TCM (oral) TCM (topical) 4 weeks 2 weeks Abbreviations: BL = Baseline; IM = intramuscular; IV = intravenous; PUVA = psoralen plus ultraviolet light A; TCM = traditional Chinese medicine; UVA = ultraviolet light A; UVB = ultraviolet light B. 1 Unless the patient has been on a stable dose for at least 6 months prior to BL Visit without exacerbation of psoriasis.
• Patient has received live or attenuated vaccines during the 4 weeks prior to BL visit or has the intention of receiving a live or attenuated vaccine at any time during the study.
• Note: Inactivated (non-live and non-attenuated) vaccines are allowed.
• 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 patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.
• 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 or designee, will not put the patient at further risk or hinder the patient's ability to maintain compliance with study drug and the visit schedule.

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (30)

North Estonia Medical Centre

Tallinn, 13419, Estonia

Location

Innomedica OU

Tallinn, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

Aleksandre Aladashvili Clinic, LLC

Tbilisi, 0102, Georgia

Location

J.S.C. Curatio

Tbilisi, 0114, Georgia

Location

LEPL The First University Clinic of Tbilisi State Medical University

Tbilisi, 0141, Georgia

Location

Scientific Research National Center of Dermatology and Venereology LLC

Tbilisi, 0159, Georgia

Location

Health Institute LLC

Tbilisi, 0160, Georgia

Location

David Abuladze Georgian-Italian Clinic LTD

Tbilisi, 0179, Georgia

Location

ClinicMed Daniluk, Nowak Spolka Jawna

Bialystok, 15879, Poland

Location

Centrum Badan Klinicznych PI-House Sp. Z o.o

Gdansk, 80546, Poland

Location

Centrum Medyczna ALL-MED

Krakow, 30033, Poland

Location

SGD SC

Krakow, 31147, Poland

Location

DERMED Centrum Medyczne Sp. z o.o.

Lodz, 90265, Poland

Location

Dermoklinika Centrum Medyczne s.c. M.Kierstan, J. Narbutt, A. Lesiak

Lodz, 90436, Poland

Location

ETYKA Osrodek Badan Klinicznych

Olsztyn, 11041, Poland

Location

Kliniczny Szpital Wojewódzki Nr. 1 im. Fryderyka Chopina, Klinika Detmatologii

Rzeszów, 35055, Poland

Location

MICS Centrum Medyczne Toruń

Torun, 87100, Poland

Location

Medycyna Kliniczna

Warsaw, 00874, Poland

Location

Klinika Ambroziak Dermatologia

Warsaw, 02953, Poland

Location

Royalderm Agnieszka Nawrocka

Warsaw, 02962, Poland

Location

DermMedica Sp. z o.o

Wroclaw, 51318, Poland

Location

WroMedica I. Bielicka, A. Strzalkowska s.c.

Wroclaw, 51685, Poland

Location

Communal nonprofit enterprise ,,City Dermatovenereological Dispensary #2,, Kharkiv city council

Kharkiv, 61038, Ukraine

Location

Private Medical Center Medical Clinic Blagomed LLC

Kyiv, 01023, Ukraine

Location

National Medical University named after O.O.Bohomolets

Kyiv, 01601, Ukraine

Location

Treatment and Diagnostic Center of private enterprise "Asclepius"

Lviv, 79000, Ukraine

Location

Municipal Enterprise "Rivne Regional Dermatology and Venereology Dispensary" of Rivne Regional Council

Rivne, 33028, Ukraine

Location

Treatment and Diagnostic Center of private enterprise "Asclepius"

Uzhhorod, 88000, Ukraine

Location

Military Hospital (Military Unit A3309) of Military-Medical Clinical Center of Eastern Region

Zaporizhzhya, 69063, Ukraine

Location

Related Publications (1)

• Feldman SR, Reznichenko N, Berti F, Duijzings P, Ruffieux R, Otto H, Haliduola HN, Leutz S, Stroissnig H. Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Expert Opin Biol Ther. 2023 Jul-Dec;23(8):759-771. doi: 10.1080/14712598.2023.2235263. Epub 2023 Jul 12.

  PMID: 37435850 DERIVED

MeSH Terms

Conditions

Psoriasis

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Steve Feldmann, MD, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: June 18, 2021
• Study Start: June 3, 2021
• Primary Completion: December 28, 2021
• Study Completion: October 11, 2022
• Last Updated: February 2, 2023

Record last verified: 2022-05

Locations

GE (6); UA (7); PL (14); ES (3)