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

NCT02962960 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D3461C00008
• Study Type: interventional
• Target: 36
• Locations: 4 countries
• Sites: 14

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.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (15)

• Number of Participants With Antidrug Antibody (ADA)

  Baseline to Week 52

• Number of Participants With Neutralizing Antibodies (nAb)

  Baseline to Week 52

• Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)

  Baseline to Week 52

• Change From Baseline for Vital Signs

  Baseline to Week 60

• Change From Baseline for Physical Examination

  Baseline to Week 60

Study Arms (4)

Anifrolumab - Lower dose

EXPERIMENTAL

1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50

Drug: Anifrolumab

Placebo matching for lower dose of Anifrolumab

PLACEBO COMPARATOR

1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50

Drug: Placebo

Anifrolumab - Higher dose

EXPERIMENTAL

2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50

Drug: Anifrolumab

Placebo matching for higher dose of Anifrolumab

PLACEBO COMPARATOR

2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50

Drug: Placebo

Interventions

Anifrolumab DRUG

subcutaneous administration every 2 weeks from week 0 to week 50

Anifrolumab - Higher dose; Anifrolumab - Lower dose

Placebo DRUG

subcutaneous administration every two weeks from week 0 to week 50

Placebo matching for higher dose of Anifrolumab; Placebo matching for lower dose of Anifrolumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (14)

Research Site

Thousand Oaks, California, 91360, United States

Location

Research Site

Orlando, Florida, 32810, United States

Location

Research Site

New York, New York, 10019, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Memphis, Tennessee, 38119, United States

Location

Research Site

Houston, Texas, 77034, United States

Location

Research Site

Debrecen, 4032, Hungary

Location

Research Site

Zalaegerszeg, 8900, Hungary

Location

Research Site

Bydgoszcz, 85-168, Poland

Location

Research Site

Warsaw, 00-874, Poland

Location

Research Site

Anyang-si, 14068, South Korea

Location

Research Site

Busan, 49241, South Korea

Location

Research Site

Daegu, 41944, South Korea

Location

Research Site

Gwangju, 61469, South Korea

Location

Related Publications (1)

• Bruce IN, Nami A, Schwetje E, Pierson ME, Rouse T, Chia YL, Kuruvilla D, Abreu G, Tummala R, Lindholm C. Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Rheumatol. 2021 Feb;3(2):e101-e110. doi: 10.1016/S2665-9913(20)30342-8. Epub 2020 Nov 20.

  PMID: 38279367 DERIVED

Related Links

• SAP redacted

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

anifrolumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

301-398-5799

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: November 15, 2016
• Study Start: February 14, 2017
• Primary Completion: January 22, 2018
• Study Completion: December 17, 2018
• Last Updated: January 12, 2023
• Results First Posted: December 18, 2019

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); HU (2); KR (4); PL (2)