Healthy VolunteersPhase 1NCT03849313
Pharmacokinetics, Safety and Tolerability Study of AVT02 to EU-approved and US-licensed Humira (Adalimumab)
A Phase 1 study testing Adalimumab in people with Healthy Volunteers, run by Alvotech Swiss AG at 3 sites in 2 countries.
Trial summary
This study has been designed as a multicentre, randomised, double-blind study of AVT02 in healthy adult subjects. The study will assess the PK, safety and tolerability of AVT02 compared to EU-Humira and US licenced Humira (US-Humira), when administered as a single 40 mg SC dose. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Adalimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 390 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 20 Mar 2019to 17 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female healthy adult subjects willing to sign a patient information and consent form (PICF) and able to undergo protocol related procedures.
- Age: 18 to 55 years, inclusive.
- Body Mass Index (BMI): 18.5 to 32.0 kg/m2.
- No history or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator would pose a risk to subject safety.
- 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 investigator's judgment.
- 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator.
- Negative urine drug screen and negative alcohol breath test at screening and admission.
Who cannot join
- Subjects will be excluded from the study if one or more of the following criterion are applicable:
- Evidence of clinically relevant pathology
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) used in study.
- Known history of previous exposure to adalimumab or other anti TNF-alpha molecules.
- Subjects with a recent (within 6 months of dosing) infection requiring hospitalisation or intravenous antibiotic use.
- Subjects with a recent (within 4 weeks of dosing) infection requiring oral or systemic antibiotics.
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- Subject with a history of recurrent or chronic infections.
- 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.
- Participation in a drug study within 60 days or 5 half-lives of the previous drug (if known), whichever is longer, prior to drug administration Note: Only the few inclusion/exclusion criteria are mentioned here. Subjects will be screened and randomized as per the full list of inclusion and exclusion criteria in the protocol.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
New Zealand2 sites
Auckland Clinical Studies
Auckland
Christchurch Clinical Studies Trust Limited
Christchurch, Chistchurch, 8011
About this study
Official title: Multicentre, Randomized, Double-Blind, 3-Arm, Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of AVT02 to EU-approved and US-licensed Humira® Administered as a Single Dose (40 mg Subcutaneous Injection) in Healthy Adult Volunteers (ALVOPA D FIRST)
This study has been designed as a multicentre, randomised, double-blind study of AVT02 in healthy adult subjects. The study will assess the PK, safety and tolerability of AVT02 compared to EU-Humira and US licenced Humira (US-Humira), when administered as a single 40 mg SC dose.
Read the detailed description
AVT02 is being developed as a biosimilar to Humira. EU-Humira and US-Humira have therefore been selected as the active control groups in this study.
This study is designed as a multi-center, randomised, double-blind, 3-arm parallel study of AVT02 compared to EU-Humira and US-Humira in healthy adult subjects. The study is designed to evaluate the PK, safety and tolerability of AVT02 compared to EU-Humira and US-Humira when administered as a single dose (40 mg) SC injection.
Subjects will be randomly assigned with a ratio of 1:1:1 to receive either AVT02 or EU-Humira or US-Humira on a single occasion on study Day 1. Both the site staff assessing the subjects and the subjects themselves will be blinded to the treatments being administered.
The study consists of a screening period, admission and treatment period, assessment period and end of study visit. Subjects will undertake a screening visit between Day -28 and Day -1 to determine eligibility in the study. Those subjects that meet the eligibility criteria will be admitted to the study site on the evening prior to dosing (Day -1) when continued eligibility will be assessed.
On Day 1 prior to dosing, baseline assessments will be performed. Subjects will then be dosed according to the randomization schedule. Following dosing, PK, safety and tolerability assessments will be performed according to the study schedule (Table 6Table 6). Subjects will remain confined to the study site from Day -1 to Day 3 (48 hours post-dose). Subjects will return to the study site on Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 12, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 and Day 57.
An end of study visit will occur at study Day 64 for final study assessments
- Conditions
- Healthy Volunteers
- Being tested
- Adalimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabDrug
Also called Humira ATC code L04AB04
AVT02, a proposed similar biological product (biosimilar) of Humira which contains adalimumab . Adalimumab is a recombinant, fully human monoclonal immunoglobulin G1 (IgG1) antibody that binds specifically and with high affinity to the soluble and transmembrane forms of tumor necrosis factor (TNF)-α thereby inhibiting the binding of TNF-α with its receptor, and inhibiting TNF -α's biological function.
Tumor necrosis factor-α is a naturally occurring cytokine that is key to normal inflammatory and immune responses. Elevated levels of TNF-α are found in the synovial fluid of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis patients and psoriasis plaques and play an important role in both the pathologic inflammation and joint destruction that are hallmarks of these inflammatory diseases
| Study group | Role | What they receive |
|---|---|---|
| AVT02 100mg/mL | Experimental | Biosimilar Adalimumab AVT02 Receives: Drug: Adalimumab |
| EU-Humira 100mg/mL | Active comparator | EU Approved Adalimumab originator Humira Receives: Drug: Adalimumab |
| US-Humira 100mg/mL | Active comparator | US licensed Adalimumab originator Humira Receives: Drug: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve AUC0-t
Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-t) of AVT02, US-Humira EU Humira
Measured: From baseline to day 64
Maximum serum concentration
Venous blood samples will be collected for measurement of serum concentration of AVT02, EU Humira, US-Humira
Measured: From baseline to day 64
Area under the plasma concentration-time curve AUC0-inf
Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-inf) of AVT02, US-Humira EU Humira
Measured: From baseline to day 64
Secondary outcomes (4)
Pain, Tenderness, Erythema and Swelling
The injection sites will be monitored for pain, tenderness, erythema and swelling. Each injection site reaction will be categorised using the Injection Site Intensity Grading Scheme. All four outcome measures mentioned in the title will be measured from this one scheme.
Measured: From baseline to over a 64 day period
Anti Drug Antibodies (ADRs)
Formation of Anti Drug Antibody will be measured through a validated assay.
Measured: Baseline to over a 64 day period
Adverse Events
Adverse events will be coded using MedDRA and grouped by system organ class and preferred term and summarised, by treatment group at the time of onset of the AE. The summary tables will present the number and percentage of total subjects and number of events, by system organ class and by preferred term. Injection related reactions will be listed and summarised by reaction using frequency counts and percentage, by treatment group.
Measured: From screening to day 64.
Neutralizing Antibodies (NAbs)
Formation of neutralizing antibodies measured through a validated system
Measured: From screening to day 64.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2019
- Study start20 Mar 2019
- Primary completion17 Feb 2020
- Study completion17 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 3 arm trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 390 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alvotech Swiss AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christian Schwabe, Principal investigator, Auckland Clinical Studies Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03849313
- Sponsor's protocol ID
- AVT02-GL-101
- Status last verified
- May 2022
- First submitted
- 4 Feb 2019
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wynne C, Schwabe C, Lemech C, Stroissnig H, Dias R, Sobierska J, Guenzi E, Otto H, Sattar A, Kay R, Haliduola HN, Berti F. A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST). Expert Opin Investig Drugs. 2022 Sep;31(9):965-976. doi: 10.1080/13543784.2022.2035359. Epub 2022 Feb 10.
PubMed 35107050
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Randomized, Double-Blind, 3-Arm, Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of AVT02 to EU-approved and US-licensed Humira® Administered as a Single Dose (40 mg Subcutaneous Injection) in Healthy Adult Volunteers (ALVOPA D FIRST)
- ClinicalTrials.gov ID
- NCT03849313
- Acronym / sponsor ID
- AVT02-GL-101
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 390 participants (actual)
- Lead sponsor
- Alvotech Swiss AGIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- 17 Feb 2020 (actual)
- Study completion
- 17 Feb 2020 (actual)
- First posted
- 21 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study has been designed as a multicentre, randomised, double-blind study of AVT02 in healthy adult subjects. The study will assess the PK, safety and tolerability of AVT02 compared to EU-Humira and US licenced Humira (US-Humira), when administered as a single 40 mg SC dose.
Detailed description
AVT02 is being developed as a biosimilar to Humira. EU-Humira and US-Humira have therefore been selected as the active control groups in this study.
This study is designed as a multi-center, randomised, double-blind, 3-arm parallel study of AVT02 compared to EU-Humira and US-Humira in healthy adult subjects. The study is designed to evaluate the PK, safety and tolerability of AVT02 compared to EU-Humira and US-Humira when administered as a single dose (40 mg) SC injection.
Subjects will be randomly assigned with a ratio of 1:1:1 to receive either AVT02 or EU-Humira or US-Humira on a single occasion on study Day 1. Both the site staff assessing the subjects and the subjects themselves will be blinded to the treatments being administered.
The study consists of a screening period, admission and treatment period, assessment period and end of study visit. Subjects will undertake a screening visit between Day -28 and Day -1 to determine eligibility in the study. Those subjects that meet the eligibility criteria will be admitted to the study site on the evening prior to dosing (Day -1) when continued eligibility will be assessed.
On Day 1 prior to dosing, baseline assessments will be performed. Subjects will then be dosed according to the randomization schedule. Following dosing, PK, safety and tolerability assessments will be performed according to the study schedule (Table 6Table 6). Subjects will remain confined to the study site from Day -1 to Day 3 (48 hours post-dose). Subjects will return to the study site on Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 12, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50 and Day 57.
An end of study visit will occur at study Day 64 for final study assessments
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 3 arm trial
| Arm | Type | Receives |
|---|---|---|
| AVT02 100mg/mL | Experimental | Drug: AdalimumabBiosimilar Adalimumab AVT02 |
| EU-Humira 100mg/mL | Active comparator | Drug: AdalimumabEU Approved Adalimumab originator Humira |
| US-Humira 100mg/mL | Active comparator | Drug: AdalimumabUS licensed Adalimumab originator Humira |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female healthy adult subjects willing to sign a patient information and consent form (PICF) and able to undergo protocol related procedures.
- Age: 18 to 55 years, inclusive.
- Body Mass Index (BMI): 18.5 to 32.0 kg/m2.
- No history or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator would pose a risk to subject safety.
- 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 investigator's judgment.
Key exclusion criteria (10 listed)
- Subjects will be excluded from the study if one or more of the following criterion are applicable:
- Evidence of clinically relevant pathology
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) used in study.
- Known history of previous exposure to adalimumab or other anti TNF-alpha molecules.
- Subjects with a recent (within 6 months of dosing) infection requiring hospitalisation or intravenous antibiotic use.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: Humira ATC code L04AB04AVT02, a proposed similar biological product (biosimilar) of Humira which contains adalimumab . Adalimumab is a recombinant, fully human monoclonal immunoglobulin G1 (IgG1) antibody that binds specifically and with high affinity to the soluble and transmembrane forms of tumor necrosis factor (TNF)-α thereby inhibiting the binding of TNF-α with its receptor, and inhibiting TNF -α's biological function. Tumor necrosis factor-α is a naturally occurring cytokine that is key to normal inflammatory and immune responses. Elevated levels of TNF-α are found in the synovial fluid of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis patients and psoriasis plaques and play an important role in both the pathologic inflammation and joint destruction that are hallmarks of these inflammatory diseases | Drug | AVT02 100mg/mL, EU-Humira 100mg/mL, US-Humira 100mg/mL |
Primary outcome
Area under the plasma concentration-time curve AUC0-t
Time frame: From baseline to day 64
Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-t) of AVT02, US-Humira EU Humira
Maximum serum concentration
Time frame: From baseline to day 64
Venous blood samples will be collected for measurement of serum concentration of AVT02, EU Humira, US-Humira
Area under the plasma concentration-time curve AUC0-inf
Time frame: From baseline to day 64
Venous blood samples will be collected for measurement of Area under the plasma concentration-time curve (AUC 0-inf) of AVT02, US-Humira EU Humira
4 secondary outcomes
Pain, Tenderness, Erythema and Swelling
Time frame: From baseline to over a 64 day period
Anti Drug Antibodies (ADRs)
Time frame: Baseline to over a 64 day period
Adverse Events
Time frame: From screening to day 64.
Neutralizing Antibodies (NAbs)
Time frame: From screening to day 64.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Derived from this study: PubMed 35107050Wynne C, Schwabe C, Lemech C, Stroissnig H, Dias R, Sobierska J, Guenzi E, Otto H, Sattar A, Kay R, Haliduola HN, Berti F. A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST). Expert Opin Investig Drugs. 2022 Sep;31(9):965-976. doi: 10.1080/13543784.2022.2035359. Epub 2022 Feb 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Schwabe principal investigator
Auckland Clinical Studies Limited
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adalimumab in people with Healthy Volunteers, run by Alvotech Swiss AG at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in New Zealand, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration-time curve AUC0-t (time frame: From baseline to day 64). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03849313, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.