Anifrolumab PK Study for Systemic Lupus Erythematosus (SLE)

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT05001698
Collaborator
(none)
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Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Biological: Anifrolumab
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Jul 27, 2021
Actual Primary Completion Date :
Jun 2, 2022
Actual Study Completion Date :
Jun 2, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Anifrolumab

All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Biological: Anifrolumab
intravenous infusion (IV)

Outcome Measures

Primary Outcome Measures

  1. Time to maximum observed plasma concentration (Tmax) of anifrolumab. [Day 1 to Day 141]

    To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

  2. Maximum observed plasma concentration (Cmax) of anifrolumab. [Day 1 to Day 141]

    To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

  3. Area under plasma concentration-time curve over dosing interval (AUC[tau]) of anifrolumab. [Day 1 to Day 141]

    To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

  4. Pre-dose trough concentration (Ctrough) of anifrolumab. [Day 1 to Day 141]

    To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

  5. The volume of plasma cleared of drug per unit time (CL) of anifrolumab. [Day 1 to Day 141]

    To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

Secondary Outcome Measures

  1. Incidence of adverse events [From Screening, Day 1 to Day 141]

    To characterise the safety and tolerability of anifrolumab via IV infusion.

  2. Incidence of abnormal vital signs [From Screening, Day 1 to Day 141]

    To characterise the safety and tolerability of anifrolumab via IV infusion.

  3. Incidence of abnormal laboratory parameters [Day 29, 57, 85, 113, 141]

    To characterise the safety and tolerability of anifrolumab via IV infusion.

  4. Anti-drug antibodies (ADA) [Day 1, 85, 113, 141]

    To characterise the immunogenicity of anifrolumab via IV infusion.

  5. 21-gene Type I interferon PD signature [Screening, Day 29, 85, 113, 141]

    To evaluate the IFN level change from baseline after administration of anifrolumab.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:

  5. oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;

  6. Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required;

  7. Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.

  8. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.

  9. At screening, SLEDAI-2K score ≥ 6 points.

  10. Chest imaging shows no clinically significant abnormalities (unless due to SLE).

  11. No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.

  12. 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:

  15. Intramuscular or IV glucocorticosteroids within 6 weeks;

  16. Any live or attenuated vaccine within 8 weeks;

  17. Any restricted medication listed in protocol;

  18. Blood transfusion within 4 weeks.

  19. Certain laboratory test results requirements.

  20. Concurrent enrolment in another clinical study.

  21. History or current alcohol, drug or chemical abuse within 1 year.

  22. Major surgery within 8 weeks or planned elective major surgery.

  23. Blood donation or blood loss more than 400 mL within 3 months.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Nantong China 226001
2 Research Site Shanghai China 200025
3 Research Site Shanghai China 200040

Sponsors and Collaborators

  • AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT05001698
Other Study ID Numbers:
  • D3468C00002
First Posted:
Aug 12, 2021
Last Update Posted:
Aug 18, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 18, 2022