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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

Primary Purpose

Systemic Lupus Erythematosus

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Anifrolumab
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Anifrolumab - Lower dose

Placebo matching for lower dose of Anifrolumab

Anifrolumab - Higher dose

Placebo matching for higher dose of Anifrolumab

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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).
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.
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.

Secondary Outcome Measures

Number of Participants With Antidrug Antibody (ADA)
Post-baseline ADA incidence based on the number of participants with Antidrug antibody (ADA)
Number of Participants With Neutralizing Antibodies (nAb)
Incidence of detectable nAb in post-baseline ADA positive participants.
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.
Change From Baseline for Vital Signs
Change from baseline for vital signs.
Change From Baseline for Physical Examination
Physical examination is reported as change from baseline in body weight.
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.
Value of Haemoglobin Blood Test to Detect Change From Baseline
Change from baseline in haemoglobin blood tests are reported.
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.
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline
Change from baseline in protein-creatinine ratio urinalysis tests are reported.
Value of Total Protein Urinalysis Test to Detect Change From Baseline
Change from baseline in total protein urinalysis tests are reported.
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.
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.
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.
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.
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.

Full Information

First Posted
September 23, 2016
Last Updated
December 19, 2022
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02962960
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
February 14, 2017 (Actual)
Primary Completion Date
January 22, 2018 (Actual)
Study Completion Date
December 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anifrolumab - Lower dose
Arm Type
Experimental
Arm Description
1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50
Arm Title
Placebo matching for lower dose of Anifrolumab
Arm Type
Placebo Comparator
Arm Description
1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50
Arm Title
Anifrolumab - Higher dose
Arm Type
Experimental
Arm Description
2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50
Arm Title
Placebo matching for higher dose of Anifrolumab
Arm Type
Placebo Comparator
Arm Description
2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50
Intervention Type
Drug
Intervention Name(s)
Anifrolumab
Intervention Description
subcutaneous administration every 2 weeks from week 0 to week 50
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
subcutaneous administration every two weeks from week 0 to week 50
Primary Outcome Measure Information:
Title
Maximum Concentration of Anifrolumab in Serum After First Dose
Description
Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
Time Frame
Week 0
Title
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab
Description
Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
Time Frame
Week 12
Title
21-gene Type 1 IFN Signature Score (Fold-change)
Description
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.
Time Frame
Week 12
Title
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
Description
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.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Number of Participants With Antidrug Antibody (ADA)
Description
Post-baseline ADA incidence based on the number of participants with Antidrug antibody (ADA)
Time Frame
Baseline to Week 52
Title
Number of Participants With Neutralizing Antibodies (nAb)
Description
Incidence of detectable nAb in post-baseline ADA positive participants.
Time Frame
Baseline to Week 52
Title
Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)
Description
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.
Time Frame
Baseline to Week 52
Title
Change From Baseline for Vital Signs
Description
Change from baseline for vital signs.
Time Frame
Baseline to Week 60
Title
Change From Baseline for Physical Examination
Description
Physical examination is reported as change from baseline in body weight.
Time Frame
Baseline to Week 60
Title
Change From Baseline for 12-lead ECG
Description
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.
Time Frame
Baseline to Week 52
Title
Value of Haemoglobin Blood Test to Detect Change From Baseline
Description
Change from baseline in haemoglobin blood tests are reported.
Time Frame
Baseline to Week 60
Title
Value of Haematology Blood Tests to Detect Change From Baseline
Description
Change from baseline in haematology blood tests (leucocytes [particle concentration], platelets [particle concentration]) are reported.
Time Frame
Baseline to Week 60
Title
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline
Description
Change from baseline in protein-creatinine ratio urinalysis tests are reported.
Time Frame
Baseline to Week 60
Title
Value of Total Protein Urinalysis Test to Detect Change From Baseline
Description
Change from baseline in total protein urinalysis tests are reported.
Time Frame
Baseline to Week 60
Title
Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Description
Change from baseline in clinical chemistry blood tests (Alanine Aminotransferase, Aspartate Aminotransferase) are reported.
Time Frame
Baseline to Week 60
Title
Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Description
Change from baseline in clinical creatinine chemistry blood tests (serum) are reported.
Time Frame
Baseline to Week 60
Title
Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline
Description
Change from baseline in the Erythrocyte Sedimentation Rate (ESR) inflammatory marker is reported.
Time Frame
Baseline to Week 60
Title
Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline
Description
Change from baseline in Anti-Double Stranded DNA IgG (anti-dsDNA) is reported.
Time Frame
Baseline to Week 60
Title
Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.
Description
Change from screening in Hepatitis B core antibody was monitored during the study for participants tested positive at screening.
Time Frame
Baseline to Week 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Research Site
City
Thousand Oaks
State/Province
California
ZIP/Postal Code
91360
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32810
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
Research Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Research Site
City
Zalaegerszeg
ZIP/Postal Code
8900
Country
Hungary
Facility Name
Research Site
City
Anyang-si
ZIP/Postal Code
14068
Country
Korea, Republic of
Facility Name
Research Site
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Research Site
City
Daegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Research Site
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Facility Name
Research Site
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
00-874
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D3461C00008&attachmentIdentifier=6978de0c-751d-42dc-991c-5a41f7df59f4&fileName=D3461c00008_sap_redacted.pdf&versionIdentifier=
Description
SAP redacted

Learn more about this trial

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

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