Clinical trial NCT03579823: Comparative Safety, Tolerability, Pharmacokinetic Study of AVT02 (100MG/ML) and Humira (100MG/ML) in Healthy Volunteers
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2018-07-09
Enrollment: 24
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: Single Centre, Randomised, Single-Blind, Pilot Study
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change from baseline blood pressure at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
timeFrame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
measure: Change from baseline heart rate at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
timeFrame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
measure: Change from baseline body temperature at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
timeFrame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
measure: Change from baseline electrocardiogram at 1, 2, 5, 9, 64 days post dosing
timeFrame: Predose and 1, 2, 5, 9, 64 days post dosing
measure: Change from baseline red blood cells at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline haemoglobin at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline white blood cells at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline platelets at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood gamma glutamyl transferase at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood aspartate aminotransferase at 2, 3, 5, 9, 64 days post
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood alanine aminotransferase at 2, 3, 5, 9, 64 days post
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood potassium at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood sodium at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood calcium at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood phosphate at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood chloride at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood bicarbonate at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood creatinine at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline blood bilirubin at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline international normalised ratio at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline prothrombin time at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline partial prothrombin time at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline activated partial thromboplastin time at 2, 3, 5, 9, 64 days post
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline thrombin time at 2, 3, 5, 9, 64 days post
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline urine leucocytes at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline urine glucose at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
measure: Change from baseline urine protein at 2, 3, 5, 9, 64 days post dosing
timeFrame: Predose and 2, 3, 5, 9, 64 days post dosing
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: Over 64 days
measure: Maximum serum concentration
timeFrame: Over 64 days
measure: Time to maximum serum concentration
timeFrame: Over 64 days
measure: Terminal half-life
timeFrame: Over 64 days
measure: Volume of distribution
timeFrame: Over 64 days
measure: Clearance
timeFrame: Over 64 days
measure: Incidence and titer of anti-drug antibodies to adalimumab
timeFrame: 15, 29 and 64 days after dosing
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
References: