Skip to main content
OpenTrials
Completed

NCT Number: NCT03579823

Comparative Safety, Tolerability, Pharmacokinetic Study of AVT02 (100MG/ML) and Humira (100MG/ML) in Healthy Volunteers

Adalimumab is an immunosuppressive drug that belongs to the family of anti-TNF agents. It contains a monoclonal antibody produced by biotechnology. It is designed to bind to tumor necrosis factor (TNF), a substance that is involved in several auto-immune processes. By binding to TNF, adalimumab blocks its activity, reducing the severity of various chronic inflammatory diseases including Rheumatoid Arthritis, Plaque Psoriasis and others.

Often, the high cost of biologic products may preclude access to the treatment to a big portion of the population worldwide. A biosimilar product that provides comparable safety and efficacy at more affordable cost would fulfill a broader medical need.

Humira has been available on the market for several years. Recently, a higher concentration (100 mg/mL) formulation has been introduced in major markets. Alvotech is developing AVT02, that is a proposed biosimilar of adalimumab containing high concentration (100 mg/mL) of active ingredient.

The objective of this clinical trial is to assess the similarity of AVT02 (100 mg/mL) with Humira (100 mg/mL), in terms of tolerability, safety (including immunogenicity) and compare the pharmacokinetics in healthy volunteers.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy Volunteers

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Nucleus Network

Melbourne, Victoria, 3004, Australia

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Main Inclusion Criteria:

  • Male and female healthy adult subjects willing to sign an Informed Consent Form and able to undergo protocol related procedures.
  • Age: 18 to 55 years, inclusive.
  • Body Mass Index (BMI): 19.0 to 30.0 kg per m2.
  • Medical history without major pathology, at the discretion of Principal Investigator.
  • 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 Principal Investigator's judgment.
  • Computerised 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Principal Investigator.
  • Subjects who do not smoke tobacco products or use nicotine replacement therapy or e-cigarettes.

Main Exclusion Criteria:

  • Evidence of clinically relevant pathology.
  • Unable to follow protocol instructions in the opinion of the Principal Investigator.
  • History of relevant drug and or food allergies.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
  • Known history of previous exposure to adalimumab or other anti-TNF-alpha molecules.
  • Any past or concurrent medical conditions potentially increasing the subject's risks, or would have interfered with the study evaluation, procedures, or study completion. Examples of these include medical history with evidence of clinically relevant pathology (e.g., malignancies, demyelinating disorders, herpes zoster, or hepatic, gallbladder or pancreatic diseases).
  • Presence of chronic obstructive pulmonary disease. Asthma in the childhood is allowed.
  • Evidence of a recent, within 6 months, infection requiring hospitalisation or intravenous antibiotic use.
  • 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.
  • Positive for Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HbcAb), anti- Hepatitis C virus antibodies (HCV), or anti-human immunodeficiency virus (HIV) 1 on 2 antibodies at screening.
  • Impaired liver function
  • Any persons who are an employee of the Principal Investigator, clinical centre, clinical research organisation or Sponsor, a relative of an employee of the clinical centre, the Investigator, Clinical Research Organization (CRO) or the Sponsor.
  • Other inclusion/exclusion criteria may apply.

Treatment and study plan

Adalimumab 100 MG/ML [Humira]

Drug

prefilled syringe at a concentration of 100MG/ML and delivering 40MG of adalimumab, as a single dose on day 1 day 1

AVT02 100MG/ML

Drug

prefilled syringe at a concentration of 100MG/ML delivering 40MG of AVT02, as a single dose on day 1 day 1

Primary outcomes

  1. Change from baseline blood pressure at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Measurement of blood pressure (systolic and diastolic in mm Hg)

  2. Change from baseline heart rate at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Measure of heart rate (beats per minute)

  3. Change from baseline body temperature at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing

    Measurement of oral temperature (Celsius degree)

  4. Change from baseline electrocardiogram at 1, 2, 5, 9, 64 days post dosing

    Time frame: Predose and 1, 2, 5, 9, 64 days post dosing

    Analysis of 12-lead electrocardiogram

  5. Change from baseline red blood cells at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure red blood cells count, (unit/mm3)

  6. Change from baseline haemoglobin at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure haemoglobin (g/L)

  7. Change from baseline white blood cells at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure white blood cells count, (unit/mm3)

  8. Change from baseline platelets at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure platelets count, (unit/mm3)

  9. Change from baseline blood gamma glutamyl transferase at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure gamma glutamyl transferase (UI/L)

  10. Change from baseline blood aspartate aminotransferase at 2, 3, 5, 9, 64 days post

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure aspartate aminotransferase (UI/L)

  11. Change from baseline blood alanine aminotransferase at 2, 3, 5, 9, 64 days post

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure alanine aminotransferase (UI/L)

  12. Change from baseline blood potassium at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure potassium (mmol/L)

  13. Change from baseline blood sodium at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure sodium (mmol/L)

  14. Change from baseline blood calcium at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure calcium (mmol/L)

  15. Change from baseline blood phosphate at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure phosphate (mmol/L)

  16. Change from baseline blood chloride at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure chloride (mmol/L)

  17. Change from baseline blood bicarbonate at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure bicarbonate (mmol/L)

  18. Change from baseline blood creatinine at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure creatinine (micromol/L)

  19. Change from baseline blood bilirubin at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure Bilirubin (micromol/L)

  20. Change from baseline international normalised ratio at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure international normalised ratio

  21. Change from baseline prothrombin time at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure prothrombin time (sec)

  22. Change from baseline partial prothrombin time at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure partial prothrombin time (sec)

  23. Change from baseline activated partial thromboplastin time at 2, 3, 5, 9, 64 days post

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure activated partial thromboplastin time (sec)

  24. Change from baseline thrombin time at 2, 3, 5, 9, 64 days post

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Blood collection to measure thrombin time (sec)

  25. Change from baseline urine leucocytes at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Urine sample collection to measure leucocytes

  26. Change from baseline urine glucose at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Urine sample collection to measure glucose

  27. Change from baseline urine protein at 2, 3, 5, 9, 64 days post dosing

    Time frame: Predose and 2, 3, 5, 9, 64 days post dosing

    Urine sample collection to measure protein

Secondary outcomes

  1. Area under the plasma concentration-time curve (AUC)

    Time frame: Over 64 days

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

  2. Maximum serum concentration

    Time frame: Over 64 days

    Venous blood samples will be collected for measurement of serum concentration of AVT02 and EU Humira

  3. Time to maximum serum concentration

    Time frame: Over 64 days

    Evaluation of time to maximum plasma concentration (Tmax) of AVT02 and Humira.

  4. Terminal half-life

    Time frame: Over 64 days

    Evaluation of terminal elimination half-life (T1/2) of AVT02 and Humira

  5. Volume of distribution

    Time frame: Over 64 days

    Evaluation of volume of distribution during the elimination phase (Vz) of AVT02 and Humira

  6. Clearance

    Time frame: Over 64 days

    Evaluation of total plasma clearance (CL) of AVT02 and Humira

  7. Incidence and titer of anti-drug antibodies to adalimumab

    Time frame: 15, 29 and 64 days after dosing

    A blood sample will be collected to measure antibodies to AVT02 and Humira

Sponsors and collaborators

Lead sponsor

Alvotech Swiss AG

Industry

Registry information

Official study title

Single Centre, Randomised, Single-Blind, Pilot Study to Compare the Safety, Tolerability and Pharmacokinetics of AVT02 to EU-approved Humira® as a Single Dose (40 mg) Subcutaneous Injection in Healthy Adult Subjects (ALVOPAD)

Acronym: ALVOPAD

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Jul 9, 2018
Registry last updated
Jan 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.