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

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ClinicalTrials.gov Identifier: NCT03579823
Recruitment Status : Active, not recruiting
First Posted : July 9, 2018
Last Update Posted : July 13, 2018
Sponsor:
Information provided by (Responsible Party):
Alvotech Swiss AG

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Adalimumab 100 MG/ML [Humira] Drug: AVT02 100MG/ML Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single Centre, Randomised, Single-Blind, Pilot Study
Masking: Single (Participant)
Masking Description: This study is single blind. Operators are open to treatment allocation. Subjects are blinded to the treatment allocation. In order to keep the blind, subjects are masked during the subcutaneous injection.
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : May 21, 2018
Estimated Primary Completion Date : August 15, 2018
Estimated Study Completion Date : August 15, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: AVT02 100 MG/ML
Single subcutaneous injection of 40 mg of AVT02 (100MG/ML)
Drug: AVT02 100MG/ML
prefilled syringe at a concentration of 100MG/ML delivering 40MG of AVT02, as a single dose on day 1 day 1

Active Comparator: Adalimumab 100 MG/ML [HUMIRA]
Single subcutaneous injection of 40 mg of Adalimumab (100MG/ML) [HUMIRA]
Drug: Adalimumab 100 MG/ML [Humira]
prefilled syringe at a concentration of 100MG/ML and delivering 40MG of adalimumab, as a single dose on day 1 day 1




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

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): NCT03579823


Locations
Australia, Victoria
Nucleus Network
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Alvotech Swiss AG

Responsible Party: Alvotech Swiss AG
ClinicalTrials.gov Identifier: NCT03579823     History of Changes
Other Study ID Numbers: AVT02-GL-100
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents