Clinical trial NCT03849313: Pharmacokinetics, Safety and Tolerability Study of AVT02 to EU-approved and US-licensed Humira (Adalimumab)
Official title: Multicentre, Randomized, Double-Blind, 3-Arm, Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of AVT02 to EU-approved and US-licensed Humira® Administered as a Single Dose (40 mg Subcutaneous Injection) in Healthy Adult Volunteers (ALVOPA D FIRST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 arm trial
Primary purpose: BASIC_SCIENCE

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.

Detailed description: AVT02 is being developed as a biosimilar to Humira. EU-Humira and US-Humira have therefore been selected as the active control groups in this study.

This study is designed as a multi-center, randomised, double-blind, 3-arm parallel study of AVT02 compared to EU-Humira and US-Humira in healthy adult subjects. The study is designed to evaluate the PK, safety and tolerability of AVT02 compared to EU-Humira and US-Humira when administered as a single dose (40 mg) SC injection.

Subjects will be randomly assigned with a ratio of 1:1:1 to receive either AVT02 or EU-Humira or US-Humira on a single occasion on study Day 1. Both the site staff assessing the subjects and the subjects themselves will be blinded to the treatments being administered.

The study consists of a screening period, admission and treatment period, assessment period and end of study visit. Subjects will undertake a screening visit between Day -28 and Day -1 to determine eligibility in the study. Those subjects that meet the eligibility criteria will be admitted to the study site on the evening prior to dosing (Day -1) when continued eligibility will be assessed.

On Day 1 prior to dosing, baseline assessments will be performed. Subjects will then be dosed according to the randomization schedule. Following dosing, PK, safety and tolerability assessments will be performed according to the study schedule (Table 6Table 6). Subjects will remain confined to the study site from Day -1 to Day 3 (48 hours post-dose). Subjects will return to the study site on Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 12, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 and Day 57.

An end of study visit will occur at study Day 64 for final study assessments

Eligibility criteria: Inclusion Criteria:

* 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.
* 12-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.

Exclusion Criteria

* 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.
* Participation in a drug study within 60 days or 5 half-lives of the previous drug (if known), whichever is longer, prior to drug administration Note: Only the few inclusion/exclusion criteria are mentioned here. Subjects will be screened and randomized as per the full list of inclusion and exclusion criteria in the protocol.

Primary outcomes:
measure: Area under the plasma concentration-time curve AUC0-t
timeFrame: From baseline to day 64
measure: Maximum serum concentration
timeFrame: From baseline to day 64
measure: Area under the plasma concentration-time curve AUC0-inf
timeFrame: From baseline to day 64
Secondary outcomes:
measure: Pain, Tenderness, Erythema and Swelling
timeFrame: From baseline to over a 64 day period
measure: Anti Drug Antibodies (ADRs)
timeFrame: Baseline to over a 64 day period
measure: Adverse Events
timeFrame: From screening to day 64.
measure: Neutralizing Antibodies (NAbs)
timeFrame: From screening to day 64.
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust Limited
state: Chistchurch
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
Study officials:
affiliation: Auckland Clinical Studies Limited
name: Christian Schwabe
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.