Clinical trial NCT02601625: A Study to Assess the Pharmacokinetics and Safety of Single Doses of Anifrolumab in Healthy Subjects
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety
Pharmacokinetics
Healthy Subjects
Keywords: Tolerability
Anifrolumab
Subcutaneous injection
Intravenous infusion
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-11-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab.
timeFrame: 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
measure: Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab
timeFrame: 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
measure: Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab
timeFrame: 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
measure: Safety: Number of Participants With Adverse Events (AEs)
timeFrame: From screening to final follow-up visit, up to 16 weeks
measure: Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants
timeFrame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
measure: Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants
timeFrame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
measure: Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants
timeFrame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
measure: Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants
timeFrame: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Secondary outcomes:
measure: Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA).
timeFrame: Pre-dose and at Days 5 and Day 29, up to 85 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Research Site
state: Maryland
Study officials:
affiliation: PAREXEL Early Phase Clinical Unit, Baltimore, United States of America
name: Ronald Goldwater, Dr.
role: PRINCIPAL_INVESTIGATOR
References: