Pharmacokinetics, Safety and Tolerability Study of AVT04 to EU Approved and US Licensed Stelara (Ustekinumab)

NCT04744363 | Completed Phase 1 FDA Drug

• 1 other identifier: AVT04-GL-101
• Study Type: interventional
• Target: 294
• Locations: 2 countries
• Sites: 4

Brief Summary

Protocol Title: A Phase 1, first-in-human, randomized, double-blind, single-dose, parallel-group, 3-arm study comparing the pharmacokinetic, safety, tolerability, and immunogenicity profiles of AVT04, EU approved Stelara®, and US-licensed Stelara® in healthy adult subjects Short Title: A first-in-human randomized, double-blind study to compare AVT04 with EU-approved Stelara and US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects Rationale: Alvotech (hereafter, the Sponsor) is developing AVT04 globally as a proposed biosimilar to the reference product Stelara (ustekinumab) for subcutaneous (SC) use. This is a first-in-human (FIH) clinical study with AVT04. The study aims to demonstrate pharmacokinetic (PK) similarity of the proposed biosimilar test product AVT04 and the reference products EU approved Stelara and US-licensed Stelara, in addition to evaluating the safety and tolerability of AVT04, when administered as a single 45 mg/0.5 mL SC dose.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve AUC0-inf

  Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-t) of AVT04, US Stelara EU Stelara

  From Baseline to day 92

• Maximum serum concentration

  Venous blood samples will be collected for measurement of serum concentration of AVT04, EU Stelara, US Stelara

  From Baseline to day 92

Secondary Outcomes (9)

• Ustekinumab serum concentration-time profile following single-dose administration

  From Baseline to day 92

• The secondary PK parameters to be assessed are: AUC0-t

  From Baseline to day 92

• Adverse Events

  From screening to day 92

• Immunogenicity assessments include ADAs and NAbs

  From screening to day 92

• The secondary PK parameters to be assessed are: Tmax

  From screening to day 92

Other Outcomes (1)

• The inflammatory cytokine biomarkers to be assessed include: IFN-γ, IL-22, IL-17, IL-5, IL-13, and IL-10

  From screening to day 92

Study Arms (3)

AVT04 45 mg SC

EXPERIMENTAL

Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen

Drug: Stelara PFS

US Stelara 45 mg SC

ACTIVE COMPARATOR

Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen

Drug: Stelara PFS

EU Stelara 45 mg SC

ACTIVE COMPARATOR

Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen

Drug: Stelara PFS

Interventions

Stelara PFS DRUG

Pre filled syringes filled with AVT04 and Stelara

Also known as: Ustekinumab

AVT04 45 mg SC; EU Stelara 45 mg SC; US Stelara 45 mg SC

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects are eligible to be included in the study only if all of the following criteria apply at any time starting from Screening up to Day 1 prior to IP administration:
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.
• Male or female subjects.
• Subjects must be 18 to 55 years old inclusive, at the time of signing the ICF.
• Have a body weight of 60.0 to 90.0 kg (inclusive) and body mass index (BMI) of 18.5 to 30.0 kg/m2 (inclusive).
• For Japanese subjects only Is a second-generation Japanese person living abroad and both parents and grandparents are of Japanese origin, OR Was born in Japan and both parents and grandparents are of Japanese origin.
• Medical history without major pathology, according to the PI's judgment.
• Resting supine systolic blood pressure (BP) of ≤140 mm Hg and diastolic BP of ≤90 mm Hg; other vital signs showing no clinically relevant deviations according to the PI's judgment.
• Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the PI.
• Glycated hemoglobin (HbA1c) ≤42 mmol/mol.
• Clinical safety laboratory results are within the reference ranges or showing no clinically relevant deviations as judged by the PI.
• Have a negative urine drug screen (opiates, methadone, cocaine, amphetamines \[including ecstasy and methamphetamines\], cannabinoids, barbiturates, and benzodiazepines) and a negative alcohol breath test.
• Tested negative for TB, hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), anti-hepatitis C virus (HCV) antibodies, and anti-human immunodeficiency virus (HIV) 1/2 antibodies at Screening.
• Nonsmoker or occasional smoker, ie, smokes ≤10 cigarettes (or equivalent of tobacco- or nicotine containing products) per week within 3 months of Screening, and ability and willingness to refrain from smoking during confinement at the study site.
• Ability and willingness to abstain from alcohol from 48 hours prior to drug administration, during confinement at the study site until discharge, and 24 hours prior to ambulatory visits.

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply at any time starting from Screening up to Day 1 prior to IP administration:
• Have a history of relevant drug and/or food allergies.
• Have a history of hypersensitivity to Stelara, AVT04, or their constituents.
• Have a known history of previous exposure to IL-12 and/or IL-23 inhibitors.
• Have any past or concurrent medical conditions that could potentially increase the subject's risks or that would interfere with the study evaluation, procedures, or study completion. Examples of these include medical history with evidence of clinically relevant pathology (eg, malignancies or demyelinating disorders).
• Presence of chronic obstructive pulmonary disease. Childhood asthma is allowed.
• Presence of type 1 or 2 diabetes mellitus.
• Have a known history of active or latent TB, except for subjects with documented and complete adequate treatment of TB or initiation (\>1 month) of adequate prophylaxis of latent TB, with an isoniazid-based regimen.
• Have resided or traveled in regions where tuberculosis and mycosis are endemic within 90 days before Screening, or who intend to visit such a region during the study period or within 3 months (12 weeks) after dosing.
• Any current active infections, including localized infections, or any recent history (within 1 week prior to study drug administration) of active infections (including severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] based on a positive COVID-19 polymerase chain reaction \[PCR\] nasopharyngeal swab test), cough or fever, or a history of recurrent or chronic infections.
• Participation in a clinical study with an IP within 60 days or 5 half-lives of that IP (if known), whichever is longer, prior to IP administration in the current study.
• Treatment with nontopical medications (including over-the-counter \[OTC\] medications and herbal remedies such as St. John's Wort extract) within 7 days or 5 half lives of the drug (whichever is longer) prior to IP administration, with the exception of multivitamins, vitamin C, food supplements and a limited amount of acetaminophen (up to 2 g in 24 hours, but \<1 g in 4 hours) or ibuprofen (\<1.2 g per day), which may be used throughout the study.
• Have received live vaccines during the past 4 weeks before Screening or have the intention to receive vaccination during the study period or within 13 weeks after dosing.
• Donation of more than 500 mL of blood within 8 weeks prior to drug administration.
• History of alcohol abuse (with an average intake exceeding 10 drinks/week for women and 15 drinks/week for men: 1 drink = 360 mL of beer, 150 mL of wine, or 45 mL of spirits) or drug addiction (including soft drugs like cannabis products).

Sponsors & Collaborators

• Alvotech Swiss AG: lead
• Iqvia Pty Ltd: collaborator

Study Sites (4)

Nucleus Network

Brisbane, Australia

Location

Nucleus Network Melbourne

Melbourne, 3004, Australia

Location

ACS

Auckland, 1010, New Zealand

Location

CCST

Christchurch, 8011, New Zealand

Location

Related Publications (1)

• Wynne C, Hamilton P, McLendon K, Stroissnig H, Smith M, Duijzings P, Ruffieux R, Otto H, Sattar A, Haliduola HN, Leutz S, Berti F. A randomized, double-blind, 3-arm, parallel study assessing the pharmacokinetics, safety, tolerability and immunogenicity of AVT04, an ustekinumab candidate biosimilar, in healthy adults. Expert Opin Investig Drugs. 2023 May;32(5):417-427. doi: 10.1080/13543784.2023.2215426. Epub 2023 May 23.

  PMID: 37212315 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

• Paul Duijzings, MSc

  Program Lead

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Blinded and unblinded site teams
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 1, first-in-human, randomized, double-blind, single-dose, parallel-group, 3-arm study comparing the pharmacokinetic, safety, tolerability, and immunogenicity profiles of AVT04, EU approved Stelara®, and US licensed Stelara® in healthy adult subjects

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: February 9, 2021
• Study Start: May 25, 2021
• Primary Completion: March 19, 2022
• Study Completion: March 19, 2022
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); AU (2)