Anifrolumab PK Study for Systemic Lupus Erythematosus (SLE)

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

Detailed Description
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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).

Official Title
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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)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Anifrolumab


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Aged 18 to 60 years. Body weight ≥ 40 kg. Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks. Must be receiving at least one of the following SOC regimens at screening: oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks; Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required; Oral prednisone plus immunosuppressant: start date, stability and maximum dose required. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith. At screening, SLEDAI-2K score ≥ 6 points. Chest imaging shows no clinically significant abnormalities (unless due to SLE). No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist. All participants should use effective contraception methods as protocol requests. Key exclusion criteria: 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. History or evidence of suicidal ideation or suicidal behavior. History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE. 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. History of immunodeficient condition, HIV positive included. Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable. History of severe case of herpes zoster. Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening. Acute COVID-19 infection or history of severe COVID-19. History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ. Women participants with abnormal pap smear results. 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. Known history of allergy to any component of the IP formulation or protein related products. Receipt of any of the following: Intramuscular or IV glucocorticosteroids within 6 weeks; Any live or attenuated vaccine within 8 weeks; Any restricted medication listed in protocol; Blood transfusion within 4 weeks. Certain laboratory test results requirements. Concurrent enrolment in another clinical study. History or current alcohol, drug or chemical abuse within 1 year. Major surgery within 8 weeks or planned elective major surgery. Blood donation or blood loss more than 400 mL within 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anifrolumab<br>All eligible participants will receive anifrolumab via intravenous (IV) infusion pump. | Biological: Anifrolumab<br>* intravenous infusion (IV)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, systemic lupus erythematosus, pharmacokinetic, anifrolumab