A Study to Assess the Pharmacokinetics and Safety of Single Doses of Anifrolumab in Healthy Subjects

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02601625
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 6
• Actual Duration (Months): 6.3
• Patients Per Site Per Month: 4.8

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Safety; Pharmacokinetics; Healthy Subjects	Drug: Anifrolumab SC injection (300mg); Drug: Anifrolumab IV infusion (300mg); Drug: Anifrolumab SC infusion (600mg); Drug: Anifrolumab placebo SC injection (300mg); Drug: Anifrolumab placebo IV infusion (300mg); Drug: Anifrolumab placebo SC infusion (600mg)	Phase 1

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Phase 1, Placebo-controlled, Double-blind, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Subcutaneously and Intravenously Delivered Anifrolumab in Healthy Subjects.
• Actual Study Start Date: Nov 16, 2015
• Actual Primary Completion Date: May 25, 2016
• Actual Study Completion Date: May 25, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anifrolumab 300 mg SC injections 300 mg single dose anifrolumab delivered as 2 separate 1 mL SC injections administered serially	Drug: Anifrolumab SC injection (300mg); 300 mg of anifrolumab delivered as 2 separate 1 mL SC injections administered serially on Day 1
Experimental: Anifrolumab 300 mg IV infusion 300 mg single dose anifrolumab delivered as an IV infusion over 30 minutes	Drug: Anifrolumab IV infusion (300mg); 300 mg of anifrolumab delivered as an IV infusion over 30 minutes on Day 1
Experimental: Anifrolumab 600 mg SC infusion 600 mg single dose anifrolumab or placebo delivered as 4 mL SC by infusion pump	Drug: Anifrolumab SC infusion (600mg); 600 mg of anifrolumab delivered as 4 mL SC by infusion pump on Day 1
Placebo Comparator: Placebo 300 mg SC injections 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially	Drug: Anifrolumab placebo SC injection (300mg); 300mg of placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1
Placebo Comparator: Placebo 300 mg IV infusion 300 mg single dose placebo delivered as an IV infusion over 30 minutes	Drug: Anifrolumab placebo IV infusion (300mg); 600mg of placebo delivered as an IV infusion over 30 minutes on Day 1
Placebo Comparator: Placebo 600mg SC infusion 600 mg single dose placebo delivered as 4 mL SC by infusion pump	Drug: Anifrolumab placebo SC infusion (600mg); 600 mg of placebo delivered as 4 mL SC by infusion pump on Day 1

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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

5. 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.

6. 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.

7. 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.

8. 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.

Secondary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

1. History of allergy/hypersensitivity to drugs with a similar chemical structure or class to anifrolumab or to any human gamma globulin therapy.

2. Any live or attenuated vaccine within 8 weeks prior to participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Ronald Goldwater, Dr., PAREXEL Early Phase Clinical Unit, Baltimore, United States of America

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• d3461c00006-revised-study-protocol-1_REDACTED

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02601625
• Other Study ID Numbers: D3461C00006
• First Posted: Nov 10, 2015
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by AstraZeneca: Tolerability; Anifrolumab; Subcutaneous injection; Intravenous infusion
• Additional relevant MeSH terms: Antibodies, Monoclonal

Study Results

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 Detail	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.

Arm/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion	Pooled Placebo
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Randomized participants received Anifrolumab matching placebo.
Period Title: Overall Study
STARTED	6	6	6	12
COMPLETED	6	6	5	11
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion	Pooled Placebo	Total
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Randomized participants received Anifrolumab matching placebo.	Total of all reporting groups
Overall Participants	6	6	6	12	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	27.5 (6.89)	29.7 (7.97)	26.3 (6.65)	38.4 (12.26)	32.1 (10.62)
Sex/Gender, Customized (Count of participants) [Number]
Female	4 66.7%	1 16.7%	2 33.3%	4 33.3%	11 36.7%
Male	2 33.3%	5 83.3%	4 66.7%	8 66.7%	19 63.3%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Measure Participants	6	6	6
Mean (Standard Deviation) [ug/mL]	36.22 (11.63)	82.44 (13.16)	63.86 (20.45)

2. Primary Outcome

Title	Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Measure Participants	6	6	6
Mean (Standard Deviation) [day*μg/mL]	769.1 (336.9)	902.9 (175.8)	1639 (557.7)

3. Primary Outcome

Title	Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1
Measure Participants	6	6	6
Mean (Standard Deviation) [day*μg/mL]	784.6 (330.6)	906.5 (174.9)	1828 (679.8)

4. Primary Outcome

Title	Safety: Number of Participants With Adverse Events (AEs)
Description	To assess the safety and tolerability of single doses of anifrolumab
Time Frame	From screening to final follow-up visit, up to 16 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion	Pooled Placebo	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC	Placebo 300 mg Anifrolumab IV	All Anifrolumab Participants
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Randomized participants received Anifrolumab matching placebo.	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.	Participants received Single dose of placebo 300 mg delivered as an IV infusion over 30 minutes.	Overall number of participants who received anifrolumab therapy.
Measure Participants	6	6	6	12	4	4	4	18
Number [Participants]	3 50%	2 33.3%	4 66.7%	4 33.3%	1 3.3%	2 NaN	1 NaN	9 NaN

5. Primary Outcome

Title	Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 600 mg SC Infusion	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.
Measure Participants	6	6	4	4
Immediately after dosing	1.2 (2.21)	0.0 (0.00)	8.0 (13.69)	0.0 (0.00)
10 min after injection	0.5 (0.63)	0.0 (0.00)	0.5 (1.00)	0.0 (0.00)
20 min after injection	0.3 (0.42)	0.0 (0.00)	0.4 (0.75)	0.3 (0.50)
1 hour after injection	0.2 (0.41)	0.0 (0.00)	0.3 (0.50)	0.0 (0.00)

6. Primary Outcome

Title	Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 600 mg SC Infusion	Placebo 300 mg Anifrolumab SC	Placebo 600 mg Anifrolumab SC
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.
Measure Participants	6	6	4	4
Immediately after dosing	1.3 (2.60)	14.0 (20.29)	1.3 (1.66)	0.8 (0.96)
10 min after injection	0.7 (1.21)	6.3 (14.56)	0.6 (1.25)	0.0 (0.00)
20 min after injection	0.3 (0.52)	1.5 (3.67)	0.5 (1.00)	0.3 (0.50)
1 hour after injection	0.1 (0.20)	0.0 (0.00)	0.4 (0.75)	0.0 (0.00)

7. Primary Outcome

Title	Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 600 mg SC Infusion	Placebo 300mg SC Injection	Placebo 600 mg SC Injection
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Participants received 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1.	Participants received placebo 600mg
Measure Participants	6	6	4	4
Immediately after dosing	0.3 (0.42)	17.0 (19.75)	11.5 (14.62)	20.0 (13.54)
10 minutes after injection	2.0 (4.18)	17.5 (21.39)	5.1 (9.59)	18.0 (14.99)
20 minute after injection	2.7 (4.14)	16.6 (20.81)	5.5 (9.11)	26.0 (18.55)
1 hour after injection	0.3 (0.52)	2.5 (6.12)	0.3 (0.50)	10.0 (14.14)

8. Secondary Outcome

Title	Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA).
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 300 mg IV Infusion	Anifrolumab 600 mg SC Infusion	Pooled Placebo	All Subjects
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Randomized participants received Anifrolumab matching placebo.	Overall participants.
Measure Participants	6	6	6	12	30
Day 1, pre-dose (positive)	0 0%	0 0%	0 0%	0 0%	0 0%
Day 1, pre-dose (negative)	6 100%	6 100%	6 100%	12 100%	30 100%
Day 1, pre-dose (missing)	0 0%	0 0%	0 0%	0 0%	0 0%
Day 5 (positive)	0 0%	0 0%	0 0%	0 0%	0 0%
Day 5 (negative)	6 100%	6 100%	6 100%	12 100%	30 100%
Day 5 (missing)	0 0%	0 0%	0 0%	0 0%	0 0%
Day 29 (positive)	0 0%	0 0%	0 0%	0 0%	0 0%
Day 29 (negative)	6 100%	6 100%	5 83.3%	11 91.7%	28 93.3%
Day 29 (missing)	0 0%	0 0%	1 16.7%	1 8.3%	2 6.7%
Day 85 (positive)	0 0%	1 16.7%	0 0%	0 0%	1 3.3%
Day 85 (negative)	6 100%	5 83.3%	5 83.3%	11 91.7%	27 90%
Day 85 (missing)	0 0%	0 0%	1 16.7%	1 8.3%	2 6.7%

9. Primary Outcome

Title	Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Anifrolumab 300 mg SC Injections	Anifrolumab 600 mg SC Infusion	Placebo 300mg SC Injection	Placebo 600 mg Anifrolumab SC
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.	Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1	Participants received 300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1.	Participants received single dose of placebo 600 mg delivered as 4 mL SC by infusion pump.
Measure Participants	6	6	4	4
Immediately after dosing	4.2 (10.21)	22.5 (13.69)	0.0 (0.00)	12.5 (15.00)
10 minutes after injection	0.8 (2.04)	17.3 (12.39)	0.0 (0.00)	16.5 (19.21)
20 minute after injection	0.1 (0.20)	14.1 (11.41)	0.1 (0.25)	8.0 (16.00)
1 hour after injection	0.0 (0.00)	11.7 (13.29)	0.0 (0.00)	12.5 (25.00)

Adverse Events

Time Frame	From screening to final follow-up visit, up to 16 weeks
Adverse Event Reporting Description	An adverse event (AE) is any undesirable medical condition or the deterioration of a pre existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Arm/Group Title	Anifrolumab 300 mg SC Injections		Anifrolumab 300 mg IV Infusion		Placebo 300 mg Anifrolumab SC		Placebo 300 mg IV Infusion		Placebo 600 mg Anifrolumab (SC)		Anifrolumab 600 mg SC Infusion		Pooled Placebo		All Anifrolumab Subjects
Arm/Group Description	Participants received a single dose of anifrolumab 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.		Participants received single dose of anifrolumab 300 mg delivered as an intravenous (IV) infusion over 30 minutes on Day 1		Participants received a single dose of placebo 300 mg delivered as 2 separate 1 mL subcutaneous (SC) injections administered serially on Day 1.		Participants received 300 mg single dose placebo delivered as an IV infusion over 30 minutes on Day 1.		Participants received 600 mg single dose placebo delivered as 4 mL SC by infusion pump on Day 1.		Participants received single dose of anifrolumab 600 mg delivered as 4 mL SC by infusion pump on Day 1		Randomized participants received Anifrolumab matching placebo.		Overall number of participants who received anifrolumab therapy
All Cause Mortality
	Anifrolumab 300 mg SC Injections		Anifrolumab 300 mg IV Infusion		Placebo 300 mg Anifrolumab SC		Placebo 300 mg IV Infusion		Placebo 600 mg Anifrolumab (SC)		Anifrolumab 600 mg SC Infusion		Pooled Placebo		All Anifrolumab Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		0/18 (0%)
Serious Adverse Events
	Anifrolumab 300 mg SC Injections		Anifrolumab 300 mg IV Infusion		Placebo 300 mg Anifrolumab SC		Placebo 300 mg IV Infusion		Placebo 600 mg Anifrolumab (SC)		Anifrolumab 600 mg SC Infusion		Pooled Placebo		All Anifrolumab Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Anifrolumab 300 mg SC Injections		Anifrolumab 300 mg IV Infusion		Placebo 300 mg Anifrolumab SC		Placebo 300 mg IV Infusion		Placebo 600 mg Anifrolumab (SC)		Anifrolumab 600 mg SC Infusion		Pooled Placebo		All Anifrolumab Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		2/6 (33.3%)		1/4 (25%)		1/4 (25%)		2/4 (50%)		4/6 (66.7%)		4/12 (33.3%)		9/18 (50%)
Gastrointestinal disorders
Abdominal discomfort	1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
Abdominal pain upper	0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
Diarrhoea	1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
General disorders
Chest discomfort	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Infusion site pruritus	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Peripheral swelling	0/6 (0%)		0/6 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		1/12 (8.3%)		0/18 (0%)
Vessel puncture site bruise	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Immune system disorders
Food allergy	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Infections and infestations
Upper respiratory tract infection	2/6 (33.3%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		3/18 (16.7%)
Tooth abscess	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Oral herpes	0/6 (0%)		0/6 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)		1/12 (8.3%)		0/18 (0%)
Tinea pedis	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Nervous system disorders
Headache	1/6 (16.7%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)		1/12 (8.3%)		1/18 (5.6%)
Somnolence	0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
Reproductive system and breast disorders
Menstrual disorder	1/4 (25%)		0/1 (0%)		0/1 (0%)		0/2 (0%)		0/1 (0%)		0/2 (0%)		0/4 (0%)		1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Dry throat	0/6 (0%)		2/6 (33.3%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		2/18 (11.1%)
Cough	0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
Dysphonia	0/6 (0%)		1/6 (16.7%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/12 (0%)		1/18 (5.6%)
Oropharyngeal pain	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)		0/12 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/6 (0%)		0/6 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)		1/12 (8.3%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All of the study information and data collected during the study are confidential and the property of AstraZeneca. After completion of the study, the investigator may prepare a joint publication with AstraZeneca. The investigator must undertake not to submit any part of the individual data from this study for publication without prior consent of AstraZeneca at a mutually agreed time.