Phase 2
N=36
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
Systemic Lupus Erythematosus
Bottom Line
View on ClinicalTrials.gov: NCT02962960 ↗Enrolled (actual)
36
Serious AEs
16.7%
Results posted
Dec 2019
Primary outcome: Primary: Maximum Concentration of Anifrolumab in Serum After First Dose — 14.058; 28.115 mcg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Anifrolumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Jan 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Concentration of Anifrolumab in Serum After First Dose |
14.058; 28.115 | — |
| PRIMARY Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab |
15.618; 16.926 | — |
| PRIMARY 21-gene Type 1 IFN Signature Score (Fold-change) |
3.2; 3.5; 14.3 | — |
| PRIMARY 21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change) |
77.5; 80.5; 15.1 | — |
| SECONDARY Number of Participants With Antidrug Antibody (ADA) |
1; 1; 0 | — |
| SECONDARY Number of Participants With Neutralizing Antibodies (nAb) |
0; 0; 0 | — |
| SECONDARY Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI) |
12; 11; 7; 4; 2; 0 | — |
| SECONDARY Change From Baseline for Vital Signs |
-4.1; 3; -5.8; 7.3; 2.1; -1.7 | — |
| SECONDARY Change From Baseline for Physical Examination |
-1.81; 1.37; 0.7; 0.98; -2.83; 2.52 | — |
| SECONDARY Change From Baseline for 12-lead ECG |
7; 10; 5; 3; 1; 1 | — |
| SECONDARY Value of Haemoglobin Blood Test to Detect Change From Baseline |
-0.2; 0.7; -0.5; 4.8; -1.1; 0.1 | — |
| SECONDARY Value of Haematology Blood Tests to Detect Change From Baseline |
0.491; 3.165; 0.867; 1.96; 1.041; 2.457 | — |
| SECONDARY Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline |
1.37029; -0.13007; -0.03056; 0.32764; 0.03756; -0.00465 | — |
| SECONDARY Value of Total Protein Urinalysis Test to Detect Change From Baseline |
0.7669; -0.0744; 0; 0.3443; -0.0029; -0.0011 | — |
| SECONDARY Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum) |
0.00769; -0.13003; -0.05418; 0.02501; -0.06335; -0.05607 | — |
| SECONDARY Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum) |
4.385; -3.6; 5.5; 5.25; 12.2; -7.273 | — |
| SECONDARY Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline |
-3.0; -7.2; -11.9; 5.6; -6.7; -16.0 | — |
| SECONDARY Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline |
-42.09; -84.97; -37.0; -97.33; -99.04; 8.70 | — |
| SECONDARY Number of Participants With Positive Hepatitis B Core Antibody Post-baseline. |
— | — |
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
- 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
Data sourced from ClinicalTrials.gov (NCT02962960). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.