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

NCT02601625 | Completed Phase 1 Results

• 1 other identifier: D3461C00006
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Safety; Pharmacokinetics; Healthy Subjects

Keywords

Tolerability; Anifrolumab; Subcutaneous injection; Intravenous infusion

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (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

Study Arms (6)

Anifrolumab 300 mg SC injections

EXPERIMENTAL

300 mg single dose anifrolumab delivered as 2 separate 1 mL SC injections administered serially

Drug: Anifrolumab SC injection (300mg)

Anifrolumab 300 mg IV infusion

EXPERIMENTAL

300 mg single dose anifrolumab delivered as an IV infusion over 30 minutes

Drug: Anifrolumab IV infusion (300mg)

Anifrolumab 600 mg SC infusion

EXPERIMENTAL

600 mg single dose anifrolumab or placebo delivered as 4 mL SC by infusion pump

Drug: Anifrolumab SC infusion (600mg)

Placebo 300 mg SC injections

PLACEBO COMPARATOR

300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially

Drug: Anifrolumab placebo SC injection (300mg)

Placebo 300 mg IV infusion

PLACEBO COMPARATOR

300 mg single dose placebo delivered as an IV infusion over 30 minutes

Drug: Anifrolumab placebo IV infusion (300mg)

Placebo 600mg SC infusion

PLACEBO COMPARATOR

600 mg single dose placebo delivered as 4 mL SC by infusion pump

Drug: Anifrolumab placebo SC infusion (600mg)

Interventions

Anifrolumab SC injection (300mg) DRUG

300 mg of anifrolumab delivered as 2 separate 1 mL SC injections administered serially on Day 1

Anifrolumab 300 mg SC injections

Anifrolumab IV infusion (300mg) DRUG

300 mg of anifrolumab delivered as an IV infusion over 30 minutes on Day 1

Anifrolumab 300 mg IV infusion

Anifrolumab SC infusion (600mg) DRUG

600 mg of anifrolumab delivered as 4 mL SC by infusion pump on Day 1

Anifrolumab 600 mg SC infusion

Anifrolumab placebo SC injection (300mg) DRUG

300mg of placebo delivered as 2 separate 1 mL SC injections administered serially on Day 1

Placebo 300 mg SC injections

Anifrolumab placebo IV infusion (300mg) DRUG

600mg of placebo delivered as an IV infusion over 30 minutes on Day 1

Placebo 300 mg IV infusion

Anifrolumab placebo SC infusion (600mg) DRUG

600 mg of placebo delivered as 4 mL SC by infusion pump on Day 1

Placebo 600mg SC infusion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• d3461c00006-revised-study-protocol-1\_REDACTED

Results Point of Contact

• Title: Anifrolumab Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46317761000

Study Officials

• Ronald Goldwater, Dr.

  PAREXEL Early Phase Clinical Unit, Baltimore, United States of America

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 10, 2015
• Study Start: November 16, 2015
• Primary Completion: May 25, 2016
• Study Completion: May 25, 2016
• Last Updated: February 26, 2019
• Results First Posted: February 26, 2019

Record last verified: 2019-02

Locations

US (1)