Clinical trial NCT03983876: PK, Safety and Tolerability Study of AVT02 (Adalimumab) Pre-filled Syringe (PFS) vs, AVT02 Autoinjector (AI)
Official title: Multi-center, Randomized, Open-Label, 2-Arm Parallel Study to Compare the Pharmacokinetics, Safety and Tolerability of AVT02 Administered Subcutaneously Via Prefilled Syringe or Autoinjector in Healthy Adult Volunteers (ALVOPAD PEN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Phase 1
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2019-06-12
Enrollment: 207
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: This is an open-label, 2-arm parallel study of AVT02 (Administered via a PFS either manually via an autoinjector, in healthy adult subjects. The subjects in both arms will receive the same dose of AVT02, but in two different delivery modes.
Primary purpose: TREATMENT

Brief summary: This study has been designed as a multicentre, randomised, open label study of AVT02 in healthy adult subjects. The study will assess the PK, safety and tolerability of AVT02 in Pre-Filled Syringe compared to AVT02 in Autoinjector Pen. Both arms will use single dose of 40mg of AVT02 (Adalimumab)

Detailed description: This study is designed as a multi-center, randomized, open-label, 2-arm parallel study of AVT02 administered via a PFS either manually via an autoinjector, in healthy adult subjects.

A total of 204 subjects will be recruited into this study and will be randomly assigned with a ratio of 1:1 to receive either AVT02 manually or via autoinjector. As the study is open-label, both the site staff and the subjects themselves will know which treatments are being administered.

The study consists of a screening period, admission and treatment period, assessment period and end of study (EOS) 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, tolerability and immunogenicity assessments will be performed according to the study schedule (Table 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 EOS visit will occur at study Day 64 for final study assessments. The EOS visit will also be the early termination visit if required (to be completed within 7 days of early termination wherever possible).

Eligibility criteria: Inclusion Criteria:To be eligible for study entry, subjects must satisfy all of the following criteria:

* 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: 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 (BP) of ≤150 mmHg and diastolic BP 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;
* Subjects smokes \<10 cigarettes per day within 3 months of screening and is able to abide by the smoking policy of the site;
* Ability and willingness to abstain from alcohol from 48 hours prior to IP administration, during confinement in the study site until discharge from the confinement period and 24 hours prior to ambulatory visits;
* Females must have a negative pregnancy test at screening and on admission to the study site, must not be lactating and must agree to sexual abstinence or the use effective contraception, starting at screening and continue throughout the study period up to the end of study (EOS) visit;
* Male subjects and their female spouse/partners who are of childbearing potential must agree to using 2 forms of birth control (1 of which is a highly effective method and 1 must be a barrier method), or agree to sexual abstinence, starting at screening and continue throughout the study period up to the EOS visit;
* Male subject must not donate sperm starting at screening and throughout the study period up to the EOS visit;

Exclusion Criteria:To be eligible for study entry, subjects must satisfy all of the following criteria:

* 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: 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 (BP) of ≤150 mmHg and diastolic BP 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;
* Subjects smokes \<10 cigarettes per day within 3 months of screening and is able to abide by the smoking policy of the site;
* Ability and willingness to abstain from alcohol from 48 hours prior to IP administration, during confinement in the study site until discharge from the confinement period and 24 hours prior to ambulatory visits;
* Females must have a negative pregnancy test at screening and on admission to the study site, must not be lactating and must agree to sexual abstinence or the use effective contraception, starting at screening and continue throughout the study period up to the end of study (EOS) visit;
* Male subjects and their female spouse/partners who are of childbearing potential must agree to using 2 forms of birth control (1 of which is a highly effective method and 1 must be a barrier method), or agree to sexual abstinence, starting at screening and continue throughout the study period up to the EOS visit;
* Male subject must not donate sperm starting at screening and throughout the study period up to the EOS visit;

Primary outcomes:
measure: Area under the plasma concentration-time curve AUC0-t
timeFrame: From baseline to day 64
measure: Area under the plasma concentration-time curve AUC0-inf
timeFrame: From baseline to day 64
measure: Maximum serum concentration
timeFrame: From baseline to day 64
Secondary outcomes:
measure: Pain, Tenderness, Erythema and Swelling
timeFrame: From baseline to day 64
measure: Anti Drug Antibodies (ADRs)
timeFrame: From baseline to day 64
measure: Adverse Events
timeFrame: Baseline to day 84
Other outcomes:
Locations:
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust Limited
state: Chistchurch
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
Study officials:
References:
citation: Wynne C, Schwabe C, Stroissnig H, Dias R, Sobierska J, Guenzi E, Otto H, Sattar A, Haliduola HN, Edwald E, Berti F. A multicenter, randomized, open-label, 2-arm parallel study to compare the pharmacokinetics, safety and tolerability of AVT02 administered subcutaneously via prefilled syringe or autoinjector in healthy adults. Expert Opin Biol Ther. 2023 Jul-Dec;23(8):773-780. doi: 10.1080/14712598.2022.2131391. Epub 2022 Oct 5.