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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03579823




Registration number
NCT03579823
Ethics application status
Date submitted
8/06/2018
Date registered
9/07/2018
Date last updated
18/01/2019

Titles & IDs
Public title
Comparative Safety, Tolerability, Pharmacokinetic Study of AVT02 (100MG/ML) and Humira (100MG/ML) in Healthy Volunteers
Scientific 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)
Secondary ID [1] 0 0
AVT02-GL-100
Universal Trial Number (UTN)
Trial acronym
ALVOPAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Adalimumab 100 MG/ML [Humira]
Treatment: Drugs - AVT02 100MG/ML

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

Active Comparator: Adalimumab 100 MG/ML [HUMIRA] - Single subcutaneous injection of 40 mg of Adalimumab (100MG/ML) [HUMIRA]


Treatment: Drugs: 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

Treatment: Drugs: AVT02 100MG/ML
prefilled syringe at a concentration of 100MG/ML delivering 40MG of AVT02, as a single dose on day 1 day 1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline blood pressure at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Timepoint [1] 0 0
Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Primary outcome [2] 0 0
Change from baseline heart rate at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Timepoint [2] 0 0
Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Primary outcome [3] 0 0
Change from baseline body temperature at 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Timepoint [3] 0 0
Predose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 64 days post dosing
Primary outcome [4] 0 0
Change from baseline electrocardiogram at 1, 2, 5, 9, 64 days post dosing
Timepoint [4] 0 0
Predose and 1, 2, 5, 9, 64 days post dosing
Primary outcome [5] 0 0
Change from baseline red blood cells at 2, 3, 5, 9, 64 days post dosing
Timepoint [5] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [6] 0 0
Change from baseline haemoglobin at 2, 3, 5, 9, 64 days post dosing
Timepoint [6] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [7] 0 0
Change from baseline white blood cells at 2, 3, 5, 9, 64 days post dosing
Timepoint [7] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [8] 0 0
Change from baseline platelets at 2, 3, 5, 9, 64 days post dosing
Timepoint [8] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [9] 0 0
Change from baseline blood gamma glutamyl transferase at 2, 3, 5, 9, 64 days post dosing
Timepoint [9] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [10] 0 0
Change from baseline blood aspartate aminotransferase at 2, 3, 5, 9, 64 days post
Timepoint [10] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [11] 0 0
Change from baseline blood alanine aminotransferase at 2, 3, 5, 9, 64 days post
Timepoint [11] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [12] 0 0
Change from baseline blood potassium at 2, 3, 5, 9, 64 days post dosing
Timepoint [12] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [13] 0 0
Change from baseline blood sodium at 2, 3, 5, 9, 64 days post dosing
Timepoint [13] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [14] 0 0
Change from baseline blood calcium at 2, 3, 5, 9, 64 days post dosing
Timepoint [14] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [15] 0 0
Change from baseline blood phosphate at 2, 3, 5, 9, 64 days post dosing
Timepoint [15] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [16] 0 0
Change from baseline blood chloride at 2, 3, 5, 9, 64 days post dosing
Timepoint [16] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [17] 0 0
Change from baseline blood bicarbonate at 2, 3, 5, 9, 64 days post dosing
Timepoint [17] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [18] 0 0
Change from baseline blood creatinine at 2, 3, 5, 9, 64 days post dosing
Timepoint [18] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [19] 0 0
Change from baseline blood bilirubin at 2, 3, 5, 9, 64 days post dosing
Timepoint [19] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [20] 0 0
Change from baseline international normalised ratio at 2, 3, 5, 9, 64 days post dosing
Timepoint [20] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [21] 0 0
Change from baseline prothrombin time at 2, 3, 5, 9, 64 days post dosing
Timepoint [21] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [22] 0 0
Change from baseline partial prothrombin time at 2, 3, 5, 9, 64 days post dosing
Timepoint [22] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [23] 0 0
Change from baseline activated partial thromboplastin time at 2, 3, 5, 9, 64 days post
Timepoint [23] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [24] 0 0
Change from baseline thrombin time at 2, 3, 5, 9, 64 days post
Timepoint [24] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [25] 0 0
Change from baseline urine leucocytes at 2, 3, 5, 9, 64 days post dosing
Timepoint [25] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [26] 0 0
Change from baseline urine glucose at 2, 3, 5, 9, 64 days post dosing
Timepoint [26] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Primary outcome [27] 0 0
Change from baseline urine protein at 2, 3, 5, 9, 64 days post dosing
Timepoint [27] 0 0
Predose and 2, 3, 5, 9, 64 days post dosing
Secondary outcome [1] 0 0
Area under the plasma concentration-time curve (AUC)
Timepoint [1] 0 0
Over 64 days
Secondary outcome [2] 0 0
Maximum serum concentration
Timepoint [2] 0 0
Over 64 days
Secondary outcome [3] 0 0
Time to maximum serum concentration
Timepoint [3] 0 0
Over 64 days
Secondary outcome [4] 0 0
Terminal half-life
Timepoint [4] 0 0
Over 64 days
Secondary outcome [5] 0 0
Volume of distribution
Timepoint [5] 0 0
Over 64 days
Secondary outcome [6] 0 0
Clearance
Timepoint [6] 0 0
Over 64 days
Secondary outcome [7] 0 0
Incidence and titer of anti-drug antibodies to adalimumab
Timepoint [7] 0 0
15, 29 and 64 days after dosing

Eligibility
Key inclusion criteria
Main

- 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
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/08/2018
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alvotech Swiss AG
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03579823
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03579823