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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03849313
Recruitment Status : Completed
First Posted : February 21, 2019
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
Alvotech Swiss AG

Tracking Information
First Submitted Date  ICMJE February 4, 2019
First Posted Date  ICMJE February 21, 2019
Last Update Posted Date June 29, 2020
Actual Study Start Date  ICMJE March 20, 2019
Actual Primary Completion Date February 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2019)
  • Area under the plasma concentration-time curve AUC0-t [ Time Frame: From baseline to day 64 ]
    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
  • Maximum serum concentration [ Time Frame: From baseline to day 64 ]
    Venous blood samples will be collected for measurement of serum concentration of AVT02, EU Humira, US-Humira
  • Area under the plasma concentration-time curve AUC0-inf [ Time Frame: From baseline to day 64 ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2019)
  • Pain, Tenderness, Erythema and Swelling [ Time Frame: From baseline to over a 64 day period ]
    The injection sites will be monitored for pain, tenderness, erythema and swelling. Each injection site reaction will be categorised using the Injection Site Intensity Grading Scheme. All four outcome measures mentioned in the title will be measured from this one scheme.
  • Anti Drug Antibodies (ADRs) [ Time Frame: Baseline to over a 64 day period ]
    Formation of Anti Drug Antibody will be measured through a validated assay.
  • Adverse Events [ Time Frame: From screening to day 64. ]
    Adverse events will be coded using MedDRA and grouped by system organ class and preferred term and summarised, by treatment group at the time of onset of the AE. The summary tables will present the number and percentage of total subjects and number of events, by system organ class and by preferred term. Injection related reactions will be listed and summarised by reaction using frequency counts and percentage, by treatment group.
  • Neutralizing Antibodies (NAbs) [ Time Frame: From screening to day 64. ]
    Formation of neutralizing antibodies measured through a validated system
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Safety and Tolerability Study of AVT02 to EU-approved and US-licensed Humira (Adalimumab)
Official Title  ICMJE 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)
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
3 arm trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind
Primary Purpose: Basic Science
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE Drug: Adalimumab

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

Other Name: Humira ATC code L04AB04
Study Arms  ICMJE
  • Experimental: AVT02 100mg/mL
    Biosimilar Adalimumab AVT02
    Intervention: Drug: Adalimumab
  • Active Comparator: EU-Humira 100mg/mL
    EU Approved Adalimumab originator Humira
    Intervention: Drug: Adalimumab
  • Active Comparator: US-Humira 100mg/mL
    US licensed Adalimumab originator Humira
    Intervention: Drug: Adalimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 20, 2019)
390
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 22, 2020
Actual Primary Completion Date February 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03849313
Other Study ID Numbers  ICMJE AVT02-GL-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alvotech Swiss AG
Study Sponsor  ICMJE Alvotech Swiss AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christian Schwabe Auckland Clinical Studies Limited
PRS Account Alvotech Swiss AG
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP