Healthy Adult Subjects
Conditions
Brief summary
Rationale: Alvotech is developing AVT05 globally as a proposed biosimilar to the reference product Simponi (golimumab) for subcutaneous (SC) use. This is a first-in-human (FIH) clinical study with AVT05. The study aims to demonstrate pharmacokinetic (PK) similarity of the proposed biosimilar test product AVT05 and the reference products EU approved Simponi and US-licensed Simponi, in addition to evaluating the safety and tolerability of AVT05, when administered as a single 50 mg/0.5 mL SC dose.
Interventions
BIOLOGICALAVT05
Pre filled syringes filled with AVT05
BIOLOGICALSimponi
Pre filled syringes filled with Simponi
Sponsors
Iqvia Pty Ltd
Alvotech Swiss AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Blinded/unblinded site teams
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol. * Participants must be 18 to 55 years old (inclusive) at the time of signing the ICF. * Have a body weight of 50.0 to 90.0 kg (inclusive) and body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive).
Exclusion criteria
* Have a history of relevant drug and/or food allergies. * Known or suspected clinically relevant drug hypersensitivity to golimumab, AVT05, or any of its constituents, which in the opinion of the PI, contraindicates the participant's participation. * Have any past or concurrent medical conditions that could potentially increase the participant's risks or that would interfere with the study evaluation, procedures, or study completion. Examples of these include medical history with evidence of clinically relevant pathology (eg, malignancies or demyelinating disorders). * Previous exposure to other TNF-α inhibitors including golimumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | Day zero to day 75 - days 1 (within the hour prior to dosing and at 8 and 12 hours post-dose), 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 22, 29, 36, 43, 50, 57, 64, and 75. | The primary PK parameters to be compared is Cmax and AUC0-inf. |
Countries
New Zealand, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVT05 50mg s.c. Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen
AVT05: Pre filled syringes filled with AVT05 | 115 |
| EU Simponi 50mg s.c. Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen
Simponi: Pre filled syringes filled with Simponi | 111 |
| US Simponi 50mg s.c. Single dose Pre-filled syringe to be injected subcutaneously into thigh or abdomen
Simponi: Pre filled syringes filled with Simponi | 110 |
| Total | 336 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Other reasons | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | AVT05 50mg s.c. | Total | US Simponi 50mg s.c. | EU Simponi 50mg s.c. |
|---|---|---|---|---|
| Age, Continuous | 28.3 years STANDARD_DEVIATION 8.17 | 28.6 years STANDARD_DEVIATION 8.24 | 28.3 years STANDARD_DEVIATION 8.16 | 29.2 years STANDARD_DEVIATION 8.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 55 Participants | 19 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 43 Participants | 126 Participants | 44 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 6 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 20 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) White | 46 Participants | 121 Participants | 39 Participants | 36 Participants |
| Sex: Female, Male Female | 65 Participants | 191 Participants | 62 Participants | 64 Participants |
| Sex: Female, Male Male | 50 Participants | 145 Participants | 48 Participants | 47 Participants |
| Weight | 67.74 kilograms STANDARD_DEVIATION 9.888 | 67.42 kilograms STANDARD_DEVIATION 9.946 | 67.42 kilograms STANDARD_DEVIATION 9.736 | 67.08 kilograms STANDARD_DEVIATION 10.286 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 115 | 0 / 111 | 0 / 110 |
| other Total, other adverse events | 74 / 115 | 74 / 111 | 74 / 110 |
| serious Total, serious adverse events | 1 / 115 | 1 / 111 | 0 / 110 |
Outcome results
Primary
To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi
The primary PK parameters to be compared is Cmax and AUC0-inf.
Time frame: Day zero to day 75 - days 1 (within the hour prior to dosing and at 8 and 12 hours post-dose), 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 22, 29, 36, 43, 50, 57, 64, and 75.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AVT05 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 3453.8 ng/mL | Geometric Coefficient of Variation 52 |
| EU Simponi 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 3468.6 ng/mL | Geometric Coefficient of Variation 50 |
| US Simponi 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 3567.1 ng/mL | Geometric Coefficient of Variation 51 |
Primary
To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi
The primary PK parameter to be compared is AUC0-inf
Time frame: Day zero to day 75 - days 1 (within the hour prior to dosing and at 8 and 12 hours post-dose), 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 22, 29, 36, 43, 50, 57, 64, and 75.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AVT05 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 1423639 ng·h/mL | Geometric Coefficient of Variation 38 |
| EU Simponi 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 1362263 ng·h/mL | Geometric Coefficient of Variation 40 |
| US Simponi 50mg s.c. | To Demonstrate the PK Similarity of AVT05 With US Licensed and EU Approved Simponi and the PK of EU Approved Simponi With US Licensed Simponi | 1414744 ng·h/mL | Geometric Coefficient of Variation 37 |