Pharmacokinetics, Safety and Tolerability Study of AVT02 to EU-approved and US-licensed Humira (Adalimumab)

NCT03849313 | Completed Phase 1

• 1 other identifier: AVT02-GL-101
• Study Type: interventional
• Target: 390
• Locations: 2 countries
• Sites: 3

Brief Summary

This study has been designed as a multicentre, randomised, double-blind study of AVT02 in healthy adult subjects. The study will assess the PK, safety and tolerability of AVT02 compared to EU-Humira and US licenced Humira (US-Humira), when administered as a single 40 mg SC dose.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

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

  Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-t) of AVT02, US-Humira EU Humira

  From baseline to day 64

• Maximum serum concentration

  Venous blood samples will be collected for measurement of serum concentration of AVT02, EU Humira, US-Humira

  From baseline to day 64

• 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-inf) of AVT02, US-Humira EU Humira

  From baseline to day 64

Secondary Outcomes (4)

• Pain, Tenderness, Erythema and Swelling

  From baseline to over a 64 day period

• Anti Drug Antibodies (ADRs)

  Baseline to over a 64 day period

• Adverse Events

  From screening to day 64.

• Neutralizing Antibodies (NAbs)

  From screening to day 64.

Study Arms (3)

AVT02 100mg/mL

EXPERIMENTAL

Biosimilar Adalimumab AVT02

Drug: Adalimumab

EU-Humira 100mg/mL

ACTIVE COMPARATOR

EU Approved Adalimumab originator Humira

Drug: Adalimumab

US-Humira 100mg/mL

ACTIVE COMPARATOR

US licensed Adalimumab originator Humira

Drug: Adalimumab

Interventions

Adalimumab DRUG

AVT02, a proposed similar biological product (biosimilar) of Humira which contains adalimumab . Adalimumab is a recombinant, fully human monoclonal immunoglobulin G1 (IgG1) antibody that binds specifically and with high affinity to the soluble and transmembrane forms of tumor necrosis factor (TNF)-α thereby inhibiting the binding of TNF-α with its receptor, and inhibiting TNF -α's biological function. Tumor necrosis factor-α is a naturally occurring cytokine that is key to normal inflammatory and immune responses. Elevated levels of TNF-α are found in the synovial fluid of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis patients and psoriasis plaques and play an important role in both the pathologic inflammation and joint destruction that are hallmarks of these inflammatory diseases

Also known as: Humira ATC code L04AB04

AVT02 100mg/mL; EU-Humira 100mg/mL; US-Humira 100mg/mL

Eligibility Criteria

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

You may qualify if:

• Male or female healthy adult subjects willing to sign a patient information and consent form (PICF) and able to undergo protocol related procedures.
• Age: 18 to 55 years, inclusive.
• Body Mass Index (BMI): 18.5 to 32.0 kg/m2.
• No history or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator would pose a risk to subject safety.
• Resting supine systolic blood pressure of ≤150 mmHg and diastolic blood pressure of ≤90 mmHg. Other vital signs showing no clinically relevant deviations according to the investigator's judgment.
• lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator.
• Negative urine drug screen and negative alcohol breath test at screening and admission.

You may not qualify if:

• Subjects will be excluded from the study if one or more of the following criterion are applicable:
• Evidence of clinically relevant pathology
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) used in study.
• Known history of previous exposure to adalimumab or other anti TNF-alpha molecules.
• Subjects with a recent (within 6 months of dosing) infection requiring hospitalisation or intravenous antibiotic use.
• Subjects with a recent (within 4 weeks of dosing) infection requiring oral or systemic antibiotics.
• Subject with a history of recurrent or chronic infections.
• Subject has a positive test for tuberculosis (TB) during screening or a known history of active or latent TB, except documented and complete adequate treatment of TB.
• Having received live vaccines during the 4 weeks before screening or have the intention to receive vaccination during the study.

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (3)

Scientia Clinical Research

Sydney, New South Wales, 2031, Australia

Location

Christchurch Clinical Studies Trust Limited

Christchurch, Chistchurch, 8011, New Zealand

Location

Auckland Clinical Studies

Auckland, New Zealand

Location

Related Publications (1)

• Wynne C, Schwabe C, Lemech C, Stroissnig H, Dias R, Sobierska J, Guenzi E, Otto H, Sattar A, Kay R, Haliduola HN, Berti F. A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST). Expert Opin Investig Drugs. 2022 Sep;31(9):965-976. doi: 10.1080/13543784.2022.2035359. Epub 2022 Feb 10.

  PMID: 35107050 DERIVED

MeSH Terms

Interventions

Adalimumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christian Schwabe

  Auckland Clinical Studies Limited

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3 arm trial

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 21, 2019
• Study Start: March 20, 2019
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: May 4, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); AU (1)