Anifrolumab PK Study for Systemic Lupus Erythematosus (SLE)

A Phase I, Open-label, Single-Arm, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Anifrolumab in Chinese Participants With Systemic Lupus Erythematosus (SLE)

To assess the pharmacokinetic parameters of anifrolumab in Chinese participants with active systemic lupus erythematosus(SLE).

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Anifrolumab

Detailed Description

This is a Phase I, open-label, single-arm, multiple-dose study to evaluate the pharmacokinetics (PK), pharmacodynamics(PD), safety and tolerability profile of intravenously administered anifrolumab in Chinese participants with active SLE despite receiving standard of care (SOC).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Nantong, China, 226001
    • Research Site
  • Shanghai, China, 200025
    • Research Site
  • Shanghai, China, 200040
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key inclusion criteria:

1. Aged 18 to 60 years.
2. Body weight ≥ 40 kg.
3. Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.

4. Must be receiving at least one of the following SOC regimens at screening:

   1. oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;
   2. Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required;
   3. Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.
5. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
6. At screening, SLEDAI-2K score ≥ 6 points.
7. Chest imaging shows no clinically significant abnormalities (unless due to SLE).
8. No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.
9. All participants should use effective contraception methods as protocol requests.

Key exclusion criteria:

1. History or current diagnose of clinically significant non-SLE related vasculitis, severe or unstable neuropsychiatric SLE, active severe SLE-driven renal disease, catastrophic anti-phospholipid syndrome, inflammatory joint or skin disease other than SLE, non-SLE disease that has required treatment of certain dosage of corticosteroid.
2. History or evidence of suicidal ideation or suicidal behavior.
3. History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE.
4. History of recurrent infection requiring hospitalization and IV antibiotics, or opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.
5. History of immunodeficient condition, HIV positive included.
6. Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable.
7. History of severe case of herpes zoster.
8. Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening.
9. Acute COVID-19 infection or history of severe COVID-19.
10. History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ.
11. Women participants with abnormal pap smear results.
12. Prior receipt of anifrolumab ,or any commercially available biologic agent, or protein kinase inhibitor or any investigational product within 5 half-lives, including B cell-depleting therapy, belimumab, JAK or BTK inhibitor.
13. Known history of allergy to any component of the IP formulation or protein related products.

14. Receipt of any of the following:

    1. Intramuscular or IV glucocorticosteroids within 6 weeks;
    2. Any live or attenuated vaccine within 8 weeks;
    3. Any restricted medication listed in protocol;
    4. Blood transfusion within 4 weeks.
15. Certain laboratory test results requirements.
16. Concurrent enrolment in another clinical study.
17. History or current alcohol, drug or chemical abuse within 1 year.
18. Major surgery within 8 weeks or planned elective major surgery.
19. Blood donation or blood loss more than 400 mL within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anifrolumab; All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.	Biological: Anifrolumab; intravenous infusion (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum observed plasma concentration (Tmax) of anifrolumab.	To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.	Day 1 to Day 141
Maximum observed plasma concentration (Cmax) of anifrolumab.	To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.	Day 1 to Day 141
Area under plasma concentration-time curve over dosing interval (AUC[tau]) of anifrolumab.	To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.	Day 1 to Day 141
Pre-dose trough concentration (Ctrough) of anifrolumab.	To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.	Day 1 to Day 141
The volume of plasma cleared of drug per unit time (CL) of anifrolumab.	To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.	Day 1 to Day 141

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	To characterise the safety and tolerability of anifrolumab via IV infusion.	From Screening, Day 1 to Day 141
Incidence of abnormal vital signs	To characterise the safety and tolerability of anifrolumab via IV infusion.	From Screening, Day 1 to Day 141
Incidence of abnormal laboratory parameters	To characterise the safety and tolerability of anifrolumab via IV infusion.	Day 29, 57, 85, 113, 141
Anti-drug antibodies (ADA)	To characterise the immunogenicity of anifrolumab via IV infusion.	Day 1, 85, 113, 141
21-gene Type I interferon PD signature	To evaluate the IFN level change from baseline after administration of anifrolumab.	Screening, Day 29, 85, 113, 141

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2021
• Primary Completion (ACTUAL): June 2, 2022
• Study Completion (ACTUAL): June 2, 2022

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (ACTUAL): August 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; SLE; pharmacokinetic; anifrolumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: D3468C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No