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

NCT03579823 | Completed Phase 1 DMC

• 1 other identifier: AVT02-GL-100
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (27)

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

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

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

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

  Measure of heart rate (beats per minute)

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

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

  Measurement of oral temperature (Celsius degree)

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

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

  Analysis of 12-lead electrocardiogram

  Predose and 1, 2, 5, 9, 64 days post dosing

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

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

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure haemoglobin (g/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

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

  Predose and 2, 3, 5, 9, 64 days post dosing

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

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

  Predose and 2, 3, 5, 9, 64 days post dosing

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

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

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure aspartate aminotransferase (UI/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure alanine aminotransferase (UI/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure potassium (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure sodium (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure calcium (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure phosphate (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure chloride (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure bicarbonate (mmol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure creatinine (micromol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure Bilirubin (micromol/L)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure international normalised ratio

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure prothrombin time (sec)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure partial prothrombin time (sec)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure activated partial thromboplastin time (sec)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Blood collection to measure thrombin time (sec)

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Urine sample collection to measure leucocytes

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Urine sample collection to measure glucose

  Predose and 2, 3, 5, 9, 64 days post dosing

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

  Urine sample collection to measure protein

  Predose and 2, 3, 5, 9, 64 days post dosing

Secondary Outcomes (7)

• Area under the plasma concentration-time curve (AUC)

  Over 64 days

• Maximum serum concentration

  Over 64 days

• Time to maximum serum concentration

  Over 64 days

• Terminal half-life

  Over 64 days

• Volume of distribution

  Over 64 days

Study Arms (2)

AVT02 100 MG/ML

EXPERIMENTAL

Single subcutaneous injection of 40 mg of AVT02 (100MG/ML)

Drug: AVT02 100MG/ML

Adalimumab 100 MG/ML [HUMIRA]

ACTIVE COMPARATOR

Single subcutaneous injection of 40 mg of Adalimumab (100MG/ML) \[HUMIRA\]

Drug: Adalimumab 100 MG/ML [Humira]

Interventions

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

Adalimumab 100 MG/ML [HUMIRA]

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

AVT02 100 MG/ML

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alvotech Swiss AG: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

Adalimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Centre, Randomised, Single-Blind, Pilot Study

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: July 9, 2018
• Study Start: May 21, 2018
• Primary Completion: August 24, 2018
• Study Completion: August 24, 2018
• Last Updated: January 18, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)