Healthy Volunteer
Conditions
Brief summary
The primary objective of the study is to show equivalence in pharmacokinetics (PK) of BIIB800 and Actemra following SC administration of a single dose to healthy male participants. The secondary objective of the study is to evaluate PK over time, clinical safety, pharmacodynamic (PD) profiles and immunogenicity of BIIB800 and Actemra.
Interventions
DRUGBIIB800
Administered as specified in the treatment arm.
DRUGActemra
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Have a body mass index between 18.5 and 29.9 kilograms per meter square (kg/m\^2), inclusive. * Total body weight between 60.0 and 90.0 kg, inclusive. * Systolic blood pressure \<135 millimeters of mercury (mmHg) or \>85 mmHg at Screening, after being supine for at least 5 minutes. * No clinically significant (as determined by the Investigator) 12-lead electrocardiogram (ECG) abnormalities, no cardiac pacemaker. Key
Exclusion criteria
* History or positive test result at Screening for human immunodeficiency virus (HIV). * History of hepatitis C infection or positive test result at Screening for hepatitis C virus antibody. * Current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] and total hepatitis B core antibody \[anti-HBc\]). * Serious infection (as determined by the Investigator) within the 6 months prior to Screening. * History of systemic hypersensitivity reaction to the active drug substance, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study. * History of immunodeficiency or other clinically significant immunological disorders, or autoimmune disorders. * History of clinically significant (in the opinion of the Investigator) atopic allergy (e.g., asthma, urticaria, eczematous dermatitis, allergic rhinitis), hypersensitivity, or allergic reactions. * History of angioedema. * A positive diagnostic tuberculosis test result within 35 days prior to Day -1, defined as a positive QuantiFERON® test result or 2 successive indeterminate QuantiFERON test results. * Any prior exposure to tocilizumab or to any other agent directly acting on IL-6 or on its receptors including investigational products (e.g., siltuximab, sarilumab etc.). * Administration of immunoglobulins for anti-tetanus and anti-rabies post-exposure prophylaxis within 3 weeks prior to administration of study drug. * Any live or attenuated immunization or vaccination given within 30 days prior to Day -1 or planned to be given during the study period. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Serum Concentration (Cmax) of Tocilizumab | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) |
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tocilizumab | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) |
| Area Under the Concentration-Time Curve up to the Last Measurable Concentration (AUC0-t) of Tocilizumab | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) | From the first dose of study drug up to the end of the study (up to Day 57) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant who has received a pharmaceutical product, regardless of causal relationship with the product. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease which is temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE was defined as an AE that starts during or after dosing or starts prior to dosing and increases in severity after dosing. An SAE is any untoward medical occurrence that results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, is a medically important event. |
| Area Under the Effect-Time Curve (AUE) of Soluble Interleukin-6-Receptor (sIL-6R) | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | sIL-6R levels were determined using a validated immunoassay method based on ProteinSimple Ella. |
| Maximum Observed Effect (Emax) of sIL-6R | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Time to Emax (tEmax) of sIL-6R | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Time to Reach Cmax (Tmax) of BIIB800 and Tocilizumab | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Minimum Observed Effect (Emin) of hsCRP | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Time to Emin (tEmin) of hsCRP | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status | Day 1 to Day 57 | The ADA-positive status was determined as a participant with either a pre-existing ADA-positive status (an ADA-positive sample at baseline \[prior to administration of study treatment\]) or a treatment-induced ADA-positive status (a participant with a negative ADA sample at baseline \[pre-dose\] and at least one ADA-positive sample after the administration of the study treatment. The nAb-positive status was determined in the same manner that of ADA status. ADA and nAb were analyzed in human serum using validated electrochemiluminescence (ECL) assays based on the MesoScale Discovery platform and were measured using validated ECL methods. |
| Geometric Mean Titer of Anti-drug Antibodies (ADA) | Pre-dose, Days 15, 29, 57 | ADA titre was defined as a quasi-quantitative expression of the level of ADA in a sample. |
| AUE of High Sensitivity C-Reactive Protein (hsCRP) | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | hsCRP was determined using a particle enhanced immunoturbidometric assay. |
| Apparent Total Body Clearance (CL/F) of BIIB800 and Actemra | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
| Apparent Terminal Half-Life (t1/2) of BIIB800 and Actemra | Pre-dose on Day 1 and multiple time points post-dose (up to Day 57) | — |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Healthy male participants were enrolled in this study from 02 January 2024 to 04 October 2024 at investigative sites in the US and UK.
Pre-assignment details
Overall, 342 participants were screened, of which 300 were randomized in the study. Of the 300 participants randomized, 150 participants received a single dose of BIIB800 subcutaneous (SC) injection and 150 participants received a single dose of Actemra SC injection.
Participants by arm
| Arm | Count |
|---|---|
| BIIB800 Participants received a single dose of BIIB800 via autoinjector, administered SC in the outer area of the upper arm on Day 1 of the study. | 150 |
| Actemra Participants received a single dose of Actemra via autoinjector, administered SC in the outer area of the upper arm on Day 1 of the study. | 150 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | BIIB800 | Actemra |
|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 9.62 | 33.9 years STANDARD_DEVIATION 9.34 | 34.0 years STANDARD_DEVIATION 9.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants | 20 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 260 Participants | 130 Participants | 130 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 21 Participants | 10 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Black or African American | 48 Participants | 23 Participants | 25 Participants |
| Race/Ethnicity, Customized Race Multiple | 13 Participants | 8 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 216 Participants | 108 Participants | 108 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 300 Participants | 150 Participants | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 150 | 0 / 150 |
| other Total, other adverse events | 75 / 150 | 86 / 150 |
| serious Total, serious adverse events | 2 / 150 | 0 / 150 |
Outcome results
Primary
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tocilizumab
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PKAS included all randomized study participants with at least one evaluable PK parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tocilizumab | 2380 hours (h)*μg/ mL | Geometric Coefficient of Variation 44.9 |
| Actemra | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tocilizumab | 2240 hours (h)*μg/ mL | Geometric Coefficient of Variation 41.1 |
90.3% CI: [0.988, 1.15]
Primary
Area Under the Concentration-Time Curve up to the Last Measurable Concentration (AUC0-t) of Tocilizumab
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PKAS included all randomized study participants with at least one evaluable PK parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Area Under the Concentration-Time Curve up to the Last Measurable Concentration (AUC0-t) of Tocilizumab | 2120 h*μg/ mL | Geometric Coefficient of Variation 45.9 |
| Actemra | Area Under the Concentration-Time Curve up to the Last Measurable Concentration (AUC0-t) of Tocilizumab | 2000 h*μg/ mL | Geometric Coefficient of Variation 44 |
90.3% CI: [0.985, 1.15]
Primary
Maximum Observed Serum Concentration (Cmax) of Tocilizumab
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The pharmacokinetic analysis set (PKAS) included all randomized study participants with at least one evaluable pharmacokinetic (PK) parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Maximum Observed Serum Concentration (Cmax) of Tocilizumab | 10.5 micrograms per milliter (μg/mL) | Geometric Coefficient of Variation 43.3 |
| Actemra | Maximum Observed Serum Concentration (Cmax) of Tocilizumab | 10.0 micrograms per milliter (μg/mL) | Geometric Coefficient of Variation 41.3 |
90.3% CI: [0.974, 1.13]
Secondary
Apparent Terminal Half-Life (t1/2) of BIIB800 and Actemra
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PKAS included all randomized study participants with at least one evaluable PK parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIIB800 | Apparent Terminal Half-Life (t1/2) of BIIB800 and Actemra | 68.5 hours |
| Actemra | Apparent Terminal Half-Life (t1/2) of BIIB800 and Actemra | 68.3 hours |
Secondary
Apparent Total Body Clearance (CL/F) of BIIB800 and Actemra
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PKAS included all randomized study participants with at least one evaluable PK parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Apparent Total Body Clearance (CL/F) of BIIB800 and Actemra | 0.0680 Liter per hour (L/h) | Geometric Coefficient of Variation 44.9 |
| Actemra | Apparent Total Body Clearance (CL/F) of BIIB800 and Actemra | 0.0723 Liter per hour (L/h) | Geometric Coefficient of Variation 41.1 |
Secondary
Area Under the Effect-Time Curve (AUE) of Soluble Interleukin-6-Receptor (sIL-6R)
sIL-6R levels were determined using a validated immunoassay method based on ProteinSimple Ella.
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The pharmacodynamics analysis set (PDAS) included all randomized study participants with at least one evaluable pharmacodynamic (PD) parameter i.e., sIL-6R and/or high sensitivity C-reactive protein (hsCRP). 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Area Under the Effect-Time Curve (AUE) of Soluble Interleukin-6-Receptor (sIL-6R) | 209000 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 68400 |
| Actemra | Area Under the Effect-Time Curve (AUE) of Soluble Interleukin-6-Receptor (sIL-6R) | 202000 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 58200 |
Secondary
AUE of High Sensitivity C-Reactive Protein (hsCRP)
hsCRP was determined using a particle enhanced immunoturbidometric assay.
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PDAS included all randomized study participants with at least one evaluable PD parameter i.e., sIL-6R and/or hsCRP. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | AUE of High Sensitivity C-Reactive Protein (hsCRP) | 1190 hours*milligrams per liter (h*mg/L) | Standard Deviation 1480 |
| Actemra | AUE of High Sensitivity C-Reactive Protein (hsCRP) | 1780 hours*milligrams per liter (h*mg/L) | Standard Deviation 2570 |
Secondary
Geometric Mean Titer of Anti-drug Antibodies (ADA)
ADA titre was defined as a quasi-quantitative expression of the level of ADA in a sample.
Time frame: Pre-dose, Days 15, 29, 57
Population: The SAFS included all randomized study participants who received the study drug. 'Overall number of participants analyzed' indicates the number of participants with positive ADA. 'Number analyzed (n)' signifies the number of participants evaluable for the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BIIB800 | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Day 29 | 201.6 titre | Geometric Coefficient of Variation 41.7 |
| BIIB800 | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Day 57 | 477.3 titre | Geometric Coefficient of Variation 96.7 |
| Actemra | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Day 15 | 160.0 titre | Geometric Coefficient of Variation 0 |
| Actemra | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Day 29 | 254.0 titre | Geometric Coefficient of Variation 94.7 |
| Actemra | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Day 57 | 452.5 titre | Geometric Coefficient of Variation 152.4 |
| Unknown | Geometric Mean Titer of Anti-drug Antibodies (ADA) | Pre-dose | — titre | — |
Secondary
Maximum Observed Effect (Emax) of sIL-6R
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PDAS included all randomized study participants with at least one evaluable PD parameter i.e., sIL-6R and/or hsCRP. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Maximum Observed Effect (Emax) of sIL-6R | 459 ng/mL | Standard Deviation 99.1 |
| Actemra | Maximum Observed Effect (Emax) of sIL-6R | 452 ng/mL | Standard Deviation 90.6 |
Secondary
Minimum Observed Effect (Emin) of hsCRP
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PDAS included all randomized study participants with at least one evaluable PD parameter i.e., sIL-6R and/or hsCRP. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIIB800 | Minimum Observed Effect (Emin) of hsCRP | 0.133 milligrams per liter (mg/L) | Standard Deviation 0.124 |
| Actemra | Minimum Observed Effect (Emin) of hsCRP | 0.131 milligrams per liter (mg/L) | Standard Deviation 0.105 |
Secondary
Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status
The ADA-positive status was determined as a participant with either a pre-existing ADA-positive status (an ADA-positive sample at baseline \[prior to administration of study treatment\]) or a treatment-induced ADA-positive status (a participant with a negative ADA sample at baseline \[pre-dose\] and at least one ADA-positive sample after the administration of the study treatment. The nAb-positive status was determined in the same manner that of ADA status. ADA and nAb were analyzed in human serum using validated electrochemiluminescence (ECL) assays based on the MesoScale Discovery platform and were measured using validated ECL methods.
Time frame: Day 1 to Day 57
Population: The SAFS included all randomized study participants who received the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BIIB800 | Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status | ADA | 26 Participants |
| BIIB800 | Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status | nAb | 21 Participants |
| Actemra | Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status | ADA | 12 Participants |
| Actemra | Number of Participants With Positive Tocilizumab Anti-drug Antibodies (ADA) and Neutralizing Antibodies (nAb) Status | nAb | 9 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant who has received a pharmaceutical product, regardless of causal relationship with the product. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease which is temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE was defined as an AE that starts during or after dosing or starts prior to dosing and increases in severity after dosing. An SAE is any untoward medical occurrence that results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, is a medically important event.
Time frame: From the first dose of study drug up to the end of the study (up to Day 57)
Population: The safety analysis set (SAFS) included all randomized study participants who received the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BIIB800 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) | TEAEs | 76 Participants |
| BIIB800 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) | TESAEs | 2 Participants |
| Actemra | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) | TEAEs | 86 Participants |
| Actemra | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) | TESAEs | 0 Participants |
Secondary
Time to Emax (tEmax) of sIL-6R
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PDAS included all randomized study participants with at least one evaluable PD parameter i.e., sIL-6R and/or hsCRP. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIIB800 | Time to Emax (tEmax) of sIL-6R | 336 hours |
| Actemra | Time to Emax (tEmax) of sIL-6R | 336 hours |
Secondary
Time to Emin (tEmin) of hsCRP
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PDAS included all randomized study participants with at least one evaluable PD parameter i.e., sIL-6R and/or hsCRP. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIIB800 | Time to Emin (tEmin) of hsCRP | 72.0 hours |
| Actemra | Time to Emin (tEmin) of hsCRP | 96.0 hours |
Secondary
Time to Reach Cmax (Tmax) of BIIB800 and Tocilizumab
Time frame: Pre-dose on Day 1 and multiple time points post-dose (up to Day 57)
Population: The PKAS included all randomized study participants with at least one evaluable PK parameter. 'Overall number of participants analyzed' indicates the number of participants evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIIB800 | Time to Reach Cmax (Tmax) of BIIB800 and Tocilizumab | 84.0 hours |
| Actemra | Time to Reach Cmax (Tmax) of BIIB800 and Tocilizumab | 96.0 hours |