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

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Characterizing the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab Following Subcutaneous Administration in Adult Systemic Lupus Erythematosus Subjects With Type I Interferon Test High Result and Active Skin Manifestations.

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Anifrolumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Debrecen, Hungary, 4032
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Research Site
• Korea, Republic of
  • Anyang-si, Korea, Republic of, 14068
    • Research Site
  • Busan, Korea, Republic of, 49241
    • Research Site
  • Daegu, Korea, Republic of, 41944
    • Research Site
  • Gwangju, Korea, Republic of, 61469
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Research Site
  • Warszawa, Poland, 00-874
    • Research Site
• United States
  • California
    • Thousand Oaks, California, United States, 91360
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32810
      • Research Site
  • New York
    • New York, New York, United States, 10019
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Texas
    • Houston, Texas, United States, 77034
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab - Lower dose; 1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50	Drug: Anifrolumab; subcutaneous administration every 2 weeks from week 0 to week 50
Placebo Comparator: Placebo matching for lower dose of Anifrolumab; 1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50	Drug: Placebo; subcutaneous administration every two weeks from week 0 to week 50
Experimental: Anifrolumab - Higher dose; 2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50	Drug: Anifrolumab; subcutaneous administration every 2 weeks from week 0 to week 50
Placebo Comparator: Placebo matching for higher dose of Anifrolumab; 2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50	Drug: Placebo; subcutaneous administration every two weeks from week 0 to week 50

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration of Anifrolumab in Serum After First Dose	Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.	Week 0
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab	Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).	Week 12
21-gene Type 1 IFN Signature Score (Fold-change)	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.	Week 12
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)	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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Antidrug Antibody (ADA)	Post-baseline ADA incidence based on the number of participants with Antidrug antibody (ADA)	Baseline to Week 52
Number of Participants With Neutralizing Antibodies (nAb)	Incidence of detectable nAb in post-baseline ADA positive participants.	Baseline to Week 52
Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)	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.	Baseline to Week 52
Change From Baseline for Vital Signs	Change from baseline for vital signs.	Baseline to Week 60
Change From Baseline for Physical Examination	Physical examination is reported as change from baseline in body weight.	Baseline to Week 60
Change From Baseline for 12-lead ECG	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.	Baseline to Week 52
Value of Haemoglobin Blood Test to Detect Change From Baseline	Change from baseline in haemoglobin blood tests are reported.	Baseline to Week 60
Value of Haematology Blood Tests to Detect Change From Baseline	Change from baseline in haematology blood tests (leucocytes [particle concentration], platelets [particle concentration]) are reported.	Baseline to Week 60
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline	Change from baseline in protein-creatinine ratio urinalysis tests are reported.	Baseline to Week 60
Value of Total Protein Urinalysis Test to Detect Change From Baseline	Change from baseline in total protein urinalysis tests are reported.	Baseline to Week 60
Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)	Change from baseline in clinical chemistry blood tests (Alanine Aminotransferase, Aspartate Aminotransferase) are reported.	Baseline to Week 60
Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)	Change from baseline in clinical creatinine chemistry blood tests (serum) are reported.	Baseline to Week 60
Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline	Change from baseline in the Erythrocyte Sedimentation Rate (ESR) inflammatory marker is reported.	Baseline to Week 60
Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline	Change from baseline in Anti-Double Stranded DNA IgG (anti-dsDNA) is reported.	Baseline to Week 60
Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.	Change from screening in Hepatitis B core antibody was monitored during the study for participants tested positive at screening.	Baseline to Week 60

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• SAP redacted

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): January 22, 2018
• Study Completion (Actual): December 17, 2018

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 15, 2016

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Skin Manifestations
• Other Study ID Numbers: D3461C00008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No