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

• ClinicalTrials.gov Identifier: NCT02962960
• Recruitment Status: Completed
• First Posted: November 15, 2016
• Results First Posted: December 18, 2019
• Last Update Posted: January 12, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Anifrolumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: February 14, 2017
• Actual Primary Completion Date: January 22, 2018
• Actual Study Completion Date: December 17, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Maximum Concentration of Anifrolumab in Serum After First Dose [ Time Frame: Week 0 ]
   Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
2. Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab [ Time Frame: Week 12 ]
   Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
3. 21-gene Type 1 IFN Signature Score (Fold-change) [ Time Frame: 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.
4. 21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change) [ Time Frame: 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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Research Site

Thousand Oaks, California, United States, 91360

United States, Florida

Research Site

Orlando, Florida, United States, 32810

United States, New York

Research Site

New York, New York, United States, 10019

United States, North Carolina

Research Site

Charlotte, North Carolina, United States, 28204

United States, Tennessee

Research Site

Memphis, Tennessee, United States, 38119

United States, Texas

Research Site

Houston, Texas, United States, 77034

Hungary

Research Site

Debrecen, Hungary, 4032

Research Site

Zalaegerszeg, Hungary, 8900

Korea, Republic of

Research Site

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

Poland

Research Site

Bydgoszcz, Poland, 85-168

Research Site

Warszawa, Poland, 00-874

Sponsors and Collaborators

AstraZeneca

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] September 20, 2016

Statistical Analysis Plan  [PDF] February 27, 2018

More Information

Additional Information:

SAP redacted 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02962960
• Other Study ID Numbers: D3461C00008
• First Posted: November 15, 2016
• Results First Posted: December 18, 2019
• Last Update Posted: January 12, 2023
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Skin Manifestations; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases