Clinical trial NCT02962960: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-11-15
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Concentration of Anifrolumab in Serum After First Dose
timeFrame: Week 0
measure: Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab
timeFrame: Week 12
measure: 21-gene Type 1 IFN Signature Score (Fold-change)
timeFrame: Week 12
measure: 21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
timeFrame: Week 12
Secondary outcomes:
measure: Number of Participants With Antidrug Antibody (ADA)
timeFrame: Baseline to Week 52
measure: Number of Participants With Neutralizing Antibodies (nAb)
timeFrame: Baseline to Week 52
measure: Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)
timeFrame: Baseline to Week 52
measure: Change From Baseline for Vital Signs
timeFrame: Baseline to Week 60
measure: Change From Baseline for Physical Examination
timeFrame: Baseline to Week 60
measure: Change From Baseline for 12-lead ECG
timeFrame: Baseline to Week 52
measure: Value of Haemoglobin Blood Test to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Value of Haematology Blood Tests to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Value of Total Protein Urinalysis Test to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
timeFrame: Baseline to Week 60
measure: Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
timeFrame: Baseline to Week 60
measure: Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline
timeFrame: Baseline to Week 60
measure: Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.
timeFrame: Baseline to Week 60
Other outcomes:
Locations:
city: Thousand Oaks
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Debrecen
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
Study officials:
References: