Healthy Subjects, Pharmacokinetics, Safety
Conditions
Keywords
Tolerability, Anifrolumab, Subcutaneous injection, Intravenous infusion
Brief summary
This is a Phase I, Randomized, Placebo-Controlled, Double-Blind Study to Assess the Pharmacokinetics and Safety of anifrolumab following Single-Dose administration to healthy subjects
Detailed description
This is a Phase I placebo-controlled study to assess the pharmacokinetics, safety and tolerability of 2 doses of anifrolumab via the subcutaneous (SC) route of administration and 1 dose of anifrolumab via intravenous (IV) route in healthy subjects
Interventions
DRUGAnifrolumab SC injection (300mg)
300 mg of anifrolumab delivered as 2 separate 1 mL SC injections administered serially on Day 1
DRUGAnifrolumab IV infusion (300mg)
300 mg of anifrolumab delivered as an IV infusion over 30 minutes on Day 1
DRUGAnifrolumab SC infusion (600mg)
600 mg of anifrolumab delivered as 4 mL SC by infusion pump on Day 1
DRUGAnifrolumab placebo SC injection (300mg)
300mg of placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1
DRUGAnifrolumab placebo IV infusion (300mg)
600mg of placebo delivered as an IV infusion over 30 minutes on Day 1
DRUGAnifrolumab placebo SC infusion (600mg)
600 mg of placebo delivered as 4 mL SC by infusion pump on Day 1
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male and/or female subjects aged 18 - 55 years. 3. Females must have a negative pregnancy test at screening. 4. Females with an intact cervix must have documentation of a Pap smear with no documented malignancy. 5. Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and weigh at least 50 kg. 6. Must have adequate abdominal adipose tissue for SC injection. 7. No history of latent or active TB prior to screening. 8. A chest radiograph with no evidence of current active infection or old active TB, malignancy, or clinically significant abnormalities within 6 months prior to screening.
Exclusion criteria
1. History of any clinically significant disease or disorder which may put the subject at risk . 2. History or presence of hepatic or renal disease. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 8 weeks of participation . 4. Any clinically significant chronic or recent infection requiring hospitalization or treatment with anti-infectives. 5. History of cancer, apart from squamous or basal cell carcinoma of the skin. 6. Any clinically significant lab, vital sign or ECG abnormalities as judged by the investigator. 7. Known history of a primary immunodeficiency,HIV splenectomy or an underlying condition. 8. Any positive result on screening for hepatitis B, hepatitis C or HIV antibody. 9. History of drug abuse within 1 year of participation. 10. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 4 weeks or 5 half-lives prior to participation. 11. Previous receipt of: * Anifrolumab; * B cell-depleting therapy (including but not limited to epratuzumab, ocrelizumab, or rituximab) ≤ 52 weeks prior to screening. 12. History of allergy/hypersensitivity to drugs with a similar chemical structure or class to anifrolumab or to any human gamma globulin therapy. 13. Any live or attenuated vaccine within 8 weeks prior to participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | Induration was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported. |
| Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab. | On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days | To evaluate Cmax of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total. |
| Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab | On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days | To evaluate AUC(0-t) of anifrolumab after single administration of two doses subcutaneously and one dose intravenously Up to 13 blood samples were collected in total. |
| Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab | On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days | To evaluate AUC of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total. |
| Safety: Number of Participants With Adverse Events (AEs) | From screening to final follow-up visit, up to 16 weeks | To assess the safety and tolerability of single doses of anifrolumab |
| Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | Local injection site pain was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = no pain to 100 = worst imaginable pain). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported. |
| Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | Local injection site pruritus was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = no itching to 100 = worst imaginable itching). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported. |
| Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | Erythema was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Pre-dose and at Days 5 and Day 29, up to 85 days | Immunogenicity was assessed in all groups by the presence or absence of ADA, which was determined in serum samples using validated bioanalytical methods. The reported results are based on the confirmatory assay (positive/negative) of the ADA. The number of participants with positive, negative and missing results are reported for each time point using the safety analysis set. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at the PAREXEL Early Phase Clinical Unit Baltimore, 3001 S. Hanover St. Baltimore, MD 21225 United States of America
Pre-assignment details
All eligible participants underwent a screening period of a maximum of 28 days. During the treatment period all participants were asked to be the residents at the study site prior to the evening meal the night before dosing with anifrolumab or placebo (Day -1) until at least 48 hours after dosing; and were then discharged on the morning of Day 3.
Participants by arm
| Arm | Count |
|---|---|
| Anifrolumab 300 mg SC Injections Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1. | 6 |
| Anifrolumab 300 mg IV Infusion Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1 | 6 |
| Anifrolumab 600 mg SC Infusion Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1 | 6 |
| Pooled Placebo Randomized participants received Anifrolumab matching placebo. | 12 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Anifrolumab 300 mg SC Injections | Anifrolumab 300 mg IV Infusion | Anifrolumab 600 mg SC Infusion | Pooled Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27.5 Years STANDARD_DEVIATION 6.89 | 29.7 Years STANDARD_DEVIATION 7.97 | 26.3 Years STANDARD_DEVIATION 6.65 | 38.4 Years STANDARD_DEVIATION 12.26 | 32.1 Years STANDARD_DEVIATION 10.62 |
| Sex/Gender, Customized Female | 4 Count of participants | 1 Count of participants | 2 Count of participants | 4 Count of participants | 11 Count of participants |
| Sex/Gender, Customized Male | 2 Count of participants | 5 Count of participants | 4 Count of participants | 8 Count of participants | 19 Count of participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 12 | 0 / 18 |
| other Total, other adverse events | 3 / 6 | 2 / 6 | 1 / 4 | 1 / 4 | 2 / 4 | 4 / 6 | 4 / 12 | 9 / 18 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 12 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab
To evaluate AUC of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Time frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab | 784.6 day*μg/mL | Standard Deviation 330.6 |
| Anifrolumab 300 mg IV Infusion | Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab | 906.5 day*μg/mL | Standard Deviation 174.9 |
| Anifrolumab 600 mg SC Infusion | Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab | 1828 day*μg/mL | Standard Deviation 679.8 |
Primary
Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab
To evaluate AUC(0-t) of anifrolumab after single administration of two doses subcutaneously and one dose intravenously Up to 13 blood samples were collected in total.
Time frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab | 769.1 day*μg/mL | Standard Deviation 336.9 |
| Anifrolumab 300 mg IV Infusion | Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab | 902.9 day*μg/mL | Standard Deviation 175.8 |
| Anifrolumab 600 mg SC Infusion | Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab | 1639 day*μg/mL | Standard Deviation 557.7 |
Primary
Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab.
To evaluate Cmax of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Time frame: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
Population: The pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations that had an impact on the analysis of the PK data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab. | 36.22 ug/mL | Standard Deviation 11.63 |
| Anifrolumab 300 mg IV Infusion | Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab. | 82.44 ug/mL | Standard Deviation 13.16 |
| Anifrolumab 600 mg SC Infusion | Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab. | 63.86 ug/mL | Standard Deviation 20.45 |
Primary
Safety: Number of Participants With Adverse Events (AEs)
To assess the safety and tolerability of single doses of anifrolumab
Time frame: From screening to final follow-up visit, up to 16 weeks
Population: The safety analysis set included all participants who received at least 1 dose of investigational medicinal product (IMP) (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anifrolumab 300 mg SC Injections | Safety: Number of Participants With Adverse Events (AEs) | 3 Participants |
| Anifrolumab 300 mg IV Infusion | Safety: Number of Participants With Adverse Events (AEs) | 2 Participants |
| Anifrolumab 600 mg SC Infusion | Safety: Number of Participants With Adverse Events (AEs) | 4 Participants |
| Pooled Placebo | Safety: Number of Participants With Adverse Events (AEs) | 4 Participants |
| Placebo 300 mg Anifrolumab SC | Safety: Number of Participants With Adverse Events (AEs) | 1 Participants |
| Placebo 600 mg Anifrolumab SC | Safety: Number of Participants With Adverse Events (AEs) | 2 Participants |
| Placebo 300 mg Anifrolumab IV | Safety: Number of Participants With Adverse Events (AEs) | 1 Participants |
| All Anifrolumab Participants | Safety: Number of Participants With Adverse Events (AEs) | 9 Participants |
Primary
Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants
Erythema was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
Time frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Population: The safety analysis set included all participants who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 0.3 Millimeter | Standard Deviation 0.42 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 2.0 Millimeter | Standard Deviation 4.18 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 2.7 Millimeter | Standard Deviation 4.14 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.3 Millimeter | Standard Deviation 0.52 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 17.5 Millimeter | Standard Deviation 21.39 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 16.6 Millimeter | Standard Deviation 20.81 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 2.5 Millimeter | Standard Deviation 6.12 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 17.0 Millimeter | Standard Deviation 19.75 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 5.5 Millimeter | Standard Deviation 9.11 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 5.1 Millimeter | Standard Deviation 9.59 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.3 Millimeter | Standard Deviation 0.5 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 11.5 Millimeter | Standard Deviation 14.62 |
| Pooled Placebo | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 10.0 Millimeter | Standard Deviation 14.14 |
| Pooled Placebo | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 18.0 Millimeter | Standard Deviation 14.99 |
| Pooled Placebo | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 20.0 Millimeter | Standard Deviation 13.54 |
| Pooled Placebo | Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 26.0 Millimeter | Standard Deviation 18.55 |
Primary
Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants
Local injection site pain was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = no pain to 100 = worst imaginable pain). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Time frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Population: The safety analysis set included all participants who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | Immediately after dosing | 1.2 Millimeter | Standard Deviation 2.21 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 10 min after injection | 0.5 Millimeter | Standard Deviation 0.63 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 20 min after injection | 0.3 Millimeter | Standard Deviation 0.42 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.2 Millimeter | Standard Deviation 0.41 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 10 min after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 20 min after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | Immediately after dosing | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 20 min after injection | 0.4 Millimeter | Standard Deviation 0.75 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 10 min after injection | 0.5 Millimeter | Standard Deviation 1 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.3 Millimeter | Standard Deviation 0.5 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | Immediately after dosing | 8.0 Millimeter | Standard Deviation 13.69 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 10 min after injection | 0.0 Millimeter | Standard Deviation 0 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | Immediately after dosing | 0.0 Millimeter | Standard Deviation 0 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants | 20 min after injection | 0.3 Millimeter | Standard Deviation 0.5 |
Primary
Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants
Local injection site pruritus was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = no itching to 100 = worst imaginable itching). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Time frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Population: The safety analysis set included all participants who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | Immediately after dosing | 1.3 Millimeter | Standard Deviation 2.6 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 20 min after injection | 0.3 Millimeter | Standard Deviation 0.52 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 10 min after injection | 0.7 Millimeter | Standard Deviation 1.21 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.1 Millimeter | Standard Deviation 0.2 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 10 min after injection | 6.3 Millimeter | Standard Deviation 14.56 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 20 min after injection | 1.5 Millimeter | Standard Deviation 3.67 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | Immediately after dosing | 14.0 Millimeter | Standard Deviation 20.29 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 20 min after injection | 0.5 Millimeter | Standard Deviation 1 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.4 Millimeter | Standard Deviation 0.75 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | Immediately after dosing | 1.3 Millimeter | Standard Deviation 1.66 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 10 min after injection | 0.6 Millimeter | Standard Deviation 1.25 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 20 min after injection | 0.3 Millimeter | Standard Deviation 0.5 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 10 min after injection | 0.0 Millimeter | Standard Deviation 0 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | Immediately after dosing | 0.8 Millimeter | Standard Deviation 0.96 |
| Pooled Placebo | Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
Primary
Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants
Induration was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
Time frame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Population: The safety analysis set included all participants who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 0.1 Millimeter | Standard Deviation 0.2 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 4.2 Millimeter | Standard Deviation 10.21 |
| Anifrolumab 300 mg SC Injections | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 0.8 Millimeter | Standard Deviation 2.04 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 17.3 Millimeter | Standard Deviation 12.39 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 22.5 Millimeter | Standard Deviation 13.69 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 14.1 Millimeter | Standard Deviation 11.41 |
| Anifrolumab 300 mg IV Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 11.7 Millimeter | Standard Deviation 13.29 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 0.1 Millimeter | Standard Deviation 0.25 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 0.0 Millimeter | Standard Deviation 0 |
| Anifrolumab 600 mg SC Infusion | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 0.0 Millimeter | Standard Deviation 0 |
| Pooled Placebo | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 1 hour after injection | 12.5 Millimeter | Standard Deviation 25 |
| Pooled Placebo | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | Immediately after dosing | 12.5 Millimeter | Standard Deviation 15 |
| Pooled Placebo | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 10 minutes after injection | 16.5 Millimeter | Standard Deviation 19.21 |
| Pooled Placebo | Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants | 20 minute after injection | 8.0 Millimeter | Standard Deviation 16 |
Secondary
Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA).
Immunogenicity was assessed in all groups by the presence or absence of ADA, which was determined in serum samples using validated bioanalytical methods. The reported results are based on the confirmatory assay (positive/negative) of the ADA. The number of participants with positive, negative and missing results are reported for each time point using the safety analysis set.
Time frame: Pre-dose and at Days 5 and Day 29, up to 85 days
Population: The safety analysis set included all subjects who received at least 1 dose of IMP (anifrolumab or placebo) and for whom any safety post-dose data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (missing) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (missing) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (negative) | 6 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (positive) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (negative) | 6 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (missing) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (positive) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (negative) | 6 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (positive) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (positive) | 0 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (negative) | 6 Participants |
| Anifrolumab 300 mg SC Injections | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (missing) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (negative) | 6 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (missing) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (missing) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (negative) | 6 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (positive) | 1 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (positive) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (negative) | 6 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (positive) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (positive) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (negative) | 5 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (missing) | 0 Participants |
| Anifrolumab 300 mg IV Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (missing) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (negative) | 5 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (positive) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (negative) | 6 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (missing) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (positive) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (negative) | 6 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (missing) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (positive) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (negative) | 5 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (missing) | 1 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (positive) | 0 Participants |
| Anifrolumab 600 mg SC Infusion | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (missing) | 1 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (missing) | 0 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (positive) | 0 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (negative) | 11 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (negative) | 12 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (missing) | 1 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (positive) | 0 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (missing) | 1 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (positive) | 0 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (missing) | 0 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (negative) | 12 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (negative) | 11 Participants |
| Pooled Placebo | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (positive) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (missing) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (positive) | 1 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (positive) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (negative) | 28 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (negative) | 30 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (positive) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (missing) | 2 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 5 (negative) | 30 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (missing) | 2 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 29 (positive) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 1, pre-dose (missing) | 0 Participants |
| Placebo 300 mg Anifrolumab SC | Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA). | Day 85 (negative) | 27 Participants |