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

Phase 2

Completed

Conditions: Systemic Lupus Erythematosus

Interventions: Drug: Placebo
Drug: Anifrolumab

Registration Number: NCT02962960

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Age 18 through 70 years
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
Interferon high test result
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10
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
Must not have signs of active or latent tuberculosis (TB).
Must not be pregnant or breastfeeding.

Exclusion Criteria

Active severe or unstable neuropsychiatric SLE
Active severe SLE-driven renal disease
Any severe herpes infection at any time
Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.
Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF
History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin if successfully treated.
- Cervical cancer in situ if successfully treated

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo matching for higher dose of Anifrolumab	Placebo	2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50
Anifrolumab - Lower dose	Anifrolumab	1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50
Placebo matching for lower dose of Anifrolumab	Placebo	1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50
Anifrolumab - Higher dose	Anifrolumab	2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50

Primary Outcome Measures

Name	Time	Method
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)	Week 12	21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. For each individual participant and assessment, the level of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control, as the median of 100-(((baseline-Week 12)/baseline)\*100) for the 21 genes. At a population level, the results are presented as mean the above.
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab	Week 12	Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
Maximum Concentration of Anifrolumab in Serum After First Dose	Week 0	Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
21-gene Type 1 IFN Signature Score (Fold-change)	Week 12	21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. Levels of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control.

Secondary Outcome Measures

Name	Time	Method
Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)	Baseline to Week 60	Change from baseline in clinical creatinine chemistry blood tests (serum) are reported.
Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline	Baseline to Week 60	Change from baseline in the Erythrocyte Sedimentation Rate (ESR) inflammatory marker is reported.
Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline	Baseline to Week 60	Change from baseline in Anti-Double Stranded DNA IgG (anti-dsDNA) is reported.
Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.	Baseline to Week 60	Change from screening in Hepatitis B core antibody was monitored during the study for participants tested positive at screening.
Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)	Baseline to Week 52	Number of participants with any AEs (Adverse events), any SAEs (serious adverse events), and any adverse events of special interest (AESI) are summarized. More details are reported in the Adverse Events section.
Change From Baseline for Vital Signs	Baseline to Week 60	Change from baseline for vital signs.
Number of Participants With Antidrug Antibody (ADA)	Baseline to Week 52	Post-baseline ADA incidence based on the number of participants with Antidrug antibody (ADA)
Change From Baseline for Physical Examination	Baseline to Week 60	Physical examination is reported as change from baseline in body weight.
Change From Baseline for 12-lead ECG	Baseline to Week 52	The 12-lead ECG measurements were assessed by the investigators, and reported as normal, abnormal (not clinically significant \[NCS\]), abnormal (clinically significant \[CS\]), or not done.
Number of Participants With Neutralizing Antibodies (nAb)	Baseline to Week 52	Incidence of detectable nAb in post-baseline ADA positive participants.
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline	Baseline to Week 60	Change from baseline in protein-creatinine ratio urinalysis tests are reported.
Value of Total Protein Urinalysis Test to Detect Change From Baseline	Baseline to Week 60	Change from baseline in total protein urinalysis tests are reported.
Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)	Baseline to Week 60	Change from baseline in clinical chemistry blood tests (Alanine Aminotransferase, Aspartate Aminotransferase) are reported.
Value of Haemoglobin Blood Test to Detect Change From Baseline	Baseline to Week 60	Change from baseline in haemoglobin blood tests are reported.
Value of Haematology Blood Tests to Detect Change From Baseline	Baseline to Week 60	Change from baseline in haematology blood tests (leucocytes \[particle concentration\], platelets \[particle concentration\]) are reported.