ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02601625
Recruitment Status : Completed
First Posted : November 10, 2015
Last Update Posted : June 10, 2016
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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 Type : Interventional  (Clinical Trial)
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.
Study Start Date : November 2015
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

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




Primary Outcome Measures :
  1. Observed maximum serum concentration (Cmax) following single dose of anifrolumab [ 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 ]
    Estimation of Cmax of anifrolumab,up to 13 samples collected in total

  2. Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) following single dose of anifrolumab [ 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 ]
    Estimation of AUC(0-t) of anifrolumab, up to 13 samples collected in total

  3. Area under serum concentration-time curve from time zero extrapolated to infinity(AUCinf) following single dose of anifrolumab [ 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 ]
    Estimation of AUCinf of anifrolumab, up to 13 samples collected in total

  4. Safety and tolerability of anifrolumab by assessment of the number of adverse events and the number of subjects with adverse events [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    To assess the safety and tolerability of single doses of anifrolumab

  5. Safety and tolerability of anifrolumab by assessment of blood pressure [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    To assess the safety and tolerability of single doses of anifrolumab

  6. Safety and tolerability of anifrolumab by assessment of pulse [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    To assess the safety and tolerability of single doses of anifrolumab

  7. Safety and tolerability of anifrolumab by assessment of body temperature [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    To assess the safety and tolerability of single doses of anifrolumab

  8. Safety and tolerability of anifrolumab by assessment of electrocardigram (ECG) [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    To assess the safety and tolerability of single doses of anifrolumab

  9. Safety and tolerability of anifrolumab by assessment of physical examination [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    Including the general appearance, skin, cardiovascular, respiratory, abdomen, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal and neurological systems

  10. Safety and tolerability of anifrolumab by assessment of safety laboratory tests [ Time Frame: From screening to final follow-up visit, up to 16 weeks ]
    This is a composite of clinical chemistry, hematology and urinalysis

  11. Safety and tolerability of anifrolumab by assessment of local injection site pain (SC cohorts) [ Time Frame: After dosing on Day 1 until 48 hours post-dose ]
    A scale rating of 0-100 for injection-site assessment

  12. Safety and tolerability of anifrolumab by assessment of local injection site pruritus (SC cohorts) [ Time Frame: After dosing on Day 1 until 48 hours post-dose ]
    A scale rating of 0-100 for injection-site assessment

  13. Safety and tolerability of anifrolumab by assessment of local injection site reaction (SC cohorts) [ Time Frame: After dosing on Day 1 until 48 hours post-dose ]
    Local injection site reactions (including erythema and induration)


Secondary Outcome Measures :
  1. Immunogenicity of anifrolumab delivered as an IV infusion by the measurement of anti-drug antibody (ADA) [ Time Frame: Pre-dose and at 3 follow-up Visit, up to 85 days ]
    Up to 4 samples collected in total

  2. Immunogenicity of anifrolumab delivered as a SC injection by the measurement of anti-drug antibody (ADA) [ Time Frame: Pre-dose and at 3 follow-up Visit, up to 85 days ]
    Up to 4 samples collected in total



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02601625


Locations
United States, Maryland
Research Site
Baltimore, Maryland, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Ronald Goldwater, Dr. PAREXEL Early Phase Clinical Unit, Baltimore, United States of America

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02601625     History of Changes
Other Study ID Numbers: D3461C00006
First Posted: November 10, 2015    Key Record Dates
Last Update Posted: June 10, 2016
Last Verified: June 2016

Keywords provided by AstraZeneca:
Tolerability
Anifrolumab
Subcutaneous injection
Intravenous infusion