A Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab in Adult Type I Interferon Test High Systemic Lupus Erythematosus Subject With Active Skin Manifestations

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: Placebo; Drug: Anifrolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02962960

D3461C00008

Details and patient eligibility

About

This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result and active skin manifestations while receiving Standard of Care (SOC) treatment. In addition, the efficacy of anifrolumab on SLE skin manifestations will be characterized.

Enrollment: 36 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18 through 70 years

2. Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 American College of Rheumatology (ACR) classification criteria with at least one being:

   • Positive antinuclear antibody (ANA) or
   • Elevated anti-dsDNA antibodies or
   • anti-Smith (anti-Sm) antibodies

3. Interferon high test result

4. Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10

5. Currently receiving at least 1 of the following for treatment of SLE:

   • Oral prednisone or equivalent of ≤40 mg/day for a minimum of 2 weeks prior to signing the Informed Consent Form (ICF) and with stable dose for at least 2 weeks prior to randomization

   • Any of the following medications for at least 12 weeks prior to signing the ICF, and at a stable doses for at least 8 weeks prior to randomization: (i) Azathioprine ≤200 mg/day (ii) Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day

6. Must not have signs of active or latent tuberculosis (TB).

7. Must not be pregnant or breastfeeding.

Exclusion criteria

1. Active severe or unstable neuropsychiatric SLE

2. Active severe SLE-driven renal disease

3. Any severe herpes infection at any time

4. Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.

5. Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection

6. Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF

7. History of cancer, apart from:

   • Squamous or basal cell carcinoma of the skin if successfully treated.
   • Cervical cancer in situ if successfully treated

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 4 patient groups, including a placebo group

Anifrolumab - Lower dose

Experimental group

Description:

1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50

Treatment:

Drug: Anifrolumab

Placebo matching for lower dose of Anifrolumab

Placebo Comparator group

Description:

1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50

Treatment:

Drug: Placebo

Anifrolumab - Higher dose

Experimental group

Description:

2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50

Treatment:

Drug: Anifrolumab

Placebo matching for higher dose of Anifrolumab

Placebo Comparator group

Description:

2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50

Treatment:

Drug: Placebo