Study to Characterise Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of Anifrolumab Administered Subcutaneously (SC) or Intravenously (IV)

Official title

A Multicentre, Randomised, Open-label, Phase I Study to Characterise the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab Administered Subcutaneously or Intravenously in Participants With Systemic Lupus Erythematosus

Overview

The purpose of this study is to assess the PK, PD, and safety of anifrolumab as SC administration or IV infusion in adult participants with systemic lupus erythematosus (SLE).

Detailed description

This is a multicentre, randomised, phase I open-label study.

The study will comprise of the following:

* Screening period: Up to 30 days * Two treatment periods * Part A: Randomised SC vs IV Treatment Period: 5 weeks * Part B: Optional Extended Treatment Period: Up to 47 weeks * Safety follow-up period: 12 weeks after the final dose

Part A will include all participants who will be randomised into SC anifrolumab via autoinjector (AI) or IV anifrolumab.

Part B is an optional extended treatment period where participants will receive SC anifrolumab via accessorised prefilled syringe (aPFS).

Interventions

• Combination product Anifrolumab: SC formulation via AI
  Anifrolumab will be administered subcutaneously via an AI.
• Combination product Anifrolumab: IV formulation
  Anifrolumab will be administered intravenously.
• Combination product Anifrolumab: SC formulation via aPFS
  Anifrolumab will be administered subcutaneously via an aPFS.

Primary outcome measures

• Anifrolumab serum concentrations through Week 4 [Time frame: Up to Week 4]

Secondary outcome measures (1)

• Percentage change from baseline in Type I interferon (IFN) 21-gene expression PD marker [Time frame: Up to Week 4]

Eligibility criteria

Inclusion criteria

• Participants who have a diagnosis of adult SLE according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria for ≥ 24 weeks prior to signing the informed consent form (ICF).
• "Clinical" Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ≥ 4 points at Screening.
• Antinuclear antibody (ANA)-positive at Screening.
• Must be on stable background standard therapy with oral corticosteroids (OCS), antimalarials, and/or immunosuppressants alone or in combination.

Exclusion criteria

• Active severe or unstable neuropsychiatric SLE.
• Active severe SLE-driven renal disease.
• Known history of primary immunodeficiency, splenectomy, or any underlying condition predisposing to infection, or a positive result for Human Immunodeficiency Virus (HIV) infection confirmed by central laboratory at Screening.
• At Screening, confirmed positive test for hepatitis B serology or positive test for hepatitis C antibody.
• Any severe case of herpes zoster infection at any time prior to Week 0 (Day 1).
• Opportunistic infection requiring hospitalisation or IV antimicrobial treatment within 3 years of randomisation
• History of cancer, apart from:

• Squamous or basal cell carcinoma of the skin treated with documented curative success ≥ 3 months prior to Day 1.
• Cervical cancer in situ treated with apparent curative success ≥ 1 year prior to Day 1.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07688980 · D3466C00003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗