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

Study Overview
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Brief Summary
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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
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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

Official Title
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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.

Conditions
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Safety, Pharmacokinetics, Healthy Subjects

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures. Healthy male and/or female subjects aged 18 - 55 years. Females must have a negative pregnancy test at screening. Females with an intact cervix must have documentation of a Pap smear with no documented malignancy. Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and weigh at least 50 kg. Must have adequate abdominal adipose tissue for SC injection. No history of latent or active TB prior to screening. 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: History of any clinically significant disease or disorder which may put the subject at risk . History or presence of hepatic or renal disease. Any clinically significant illness, medical/surgical procedure, or trauma within 8 weeks of participation . Any clinically significant chronic or recent infection requiring hospitalization or treatment with anti-infectives. History of cancer, apart from squamous or basal cell carcinoma of the skin. Any clinically significant lab, vital sign or ECG abnormalities as judged by the investigator. Known history of a primary immunodeficiency,HIV splenectomy or an underlying condition. Any positive result on screening for hepatitis B, hepatitis C or HIV antibody. History of drug abuse within 1 year of participation. 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. Previous receipt of: Anifrolumab; B cell-depleting therapy (including but not limited to epratuzumab, ocrelizumab, or rituximab) ≤ 52 weeks prior to screening. History of allergy/hypersensitivity to drugs with a similar chemical structure or class to anifrolumab or to any human gamma globulin therapy. Any live or attenuated vaccine within 8 weeks prior to participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| Safety: Number of Participants With Adverse Events (AEs) | To assess the safety and tolerability of single doses of anifrolumab | From screening to final follow-up visit, up to 16 weeks | 
| 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. | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | 
| 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. | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | 
| 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. | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | 
| 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. | Immediately after dosing, at 10, 20 minutes and 1 hour after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Pre-dose and at Days 5 and Day 29, up to 85 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, Anifrolumab, Subcutaneous injection, Intravenous infusion