Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03849313
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Alvotech Swiss AG

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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Adalimumab Phase 1

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


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 390 participants
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
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)
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: AVT02 100mg/mL
Biosimilar Adalimumab AVT02
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

Active Comparator: EU-Humira 100mg/mL
EU Approved Adalimumab originator Humira
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

Active Comparator: US-Humira 100mg/mL
US licensed Adalimumab originator Humira
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




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Neutralizing Antibodies (NAbs) [ Time Frame: From screening to day 64. ]
    Formation of neutralizing antibodies measured through a validated system



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03849313


Contacts
Layout table for location contacts
Contact: Roshan Director, Clinical Operations, MSc +41786595945 roshan.dias@alvotech.com

Locations
Layout table for location information
Australia, New South Wales
Scientia Clinical Research Recruiting
Sydney, New South Wales, Australia, 2031
Contact: James Kuo, MD         
New Zealand
Christchurch Clinical Studies Trust Limited Recruiting
Christchurch, Chistchurch, New Zealand, 8011
Contact: Chris Wynne, MD         
Contact: Mark Warner         
Auckland Clinical Studies Recruiting
Auckland, New Zealand
Contact: Christian Schwabe, MD         
Sponsors and Collaborators
Alvotech Swiss AG

Layout table for additonal information
Responsible Party: Alvotech Swiss AG
ClinicalTrials.gov Identifier: NCT03849313     History of Changes
Other Study ID Numbers: AVT02-GL-101
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents