Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02446912
• Date of registration: 14/05/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
• Scientific title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Two Doses of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
• Date of first enrolment: June 9, 2015
• Target sample size: 460
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02446912
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Chile, Colombia, Germany, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Peru, Poland, Romania, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Herbert Hutman, MD
• Affiliation: Medical Science Director

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Aged 18 through 70 years at the time of screening

2. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982
revised criteria =24 weeks prior to signing the Informed Consent form (ICF)

3. Currently receiving at least 1 of the following:

1. Where prednisone is the single standard of care medication (ie, the subject is
not concurrently receiving any medication listed in inclusion criterion 3(c)), a
dose of oral prednisone =7.5 mg/day but =40 mg/day (or prednisone equivalent) for
a minimum of 8 weeks prior to Day 1. In addition, the dose of oral prednisone or
prednisone equivalent the subject is taking must be stable for a minimum of 2
weeks prior to randomisation.

2. Where prednisone is not the single standard of care medication (ie, the subject
is concurrently receiving at least one medication listed in inclusion criterion
3(c)), a dose of oral prednisone (=40 mg/day) (or prednisone equivalent) for a
minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral
prednisone or prednisone equivalent the subject is taking must be stable for a
minimum of 2 weeks prior to randomisation.

3. Any of the following medications administered for a minimum of 12 weeks prior to
signing the informed consent, and at a stable dose for a minimum of 8 weeks prior
to signing the informed consent through Day 1:

(i) Azathioprine =200 mg/day (ii) Antimalarial (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

4. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at
least 1 of which must be:

1. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay
(IFA) at the central laboratory with titre =1:80; OR

2. Anti-dsDNA antibodies at screening elevated to above normal (including
indeterminante), as per the central laboratory; OR

3. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the
central laboratory.

5. At Screening, Disease Activity Adjudication Group confirmation of:

SLEDAI-2K Criteria: SLEDAI-2K score =6 points and "Clinical" SLEDAI-2K score =4
points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the
inclusion of points attributable to any urine or laboratory results including
immunologic measures.

6. Must not have active or latent TB on either chest radiograph or by quantiferon gold
test

7. Day 1 "Clinical" SLEDAI-2K score =4 points

8. OCS dose stable for at least 2 weeks prior to randomisation

9. Stable SLE SOC treatment at the time of randomisation

10. Women of child-bearing potential must have a negative serum ß-hCG test and negative
urine pregnancy test at randomisation (Day 1) prior to administration of
investigational product

Exclusion Criteria:

1. Receipt of any investigational product (small molecule or biologic agent) within 4
weeks or 5 half-lives prior to signing of the ICF, whichever is greater

2. Receipt of any of the following:

(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to
Day 1

3. History of, or current diagnosis of, a clinically significant non SLE-related
vasculitis syndrome.

4. Active severe or unstable neuropsychiatric SLE

5. Active severe SLE-driven renal disease

6. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any
history of overlap syndromes of SLE or SSc.

7. History of, or current, inflammatory joint or skin disease other than SLE

8. History of any non-SLE disease that has required treatment with oral or parenteral
corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the
ICF

9. Known history of a primary immunodeficiency, splenectomy, or any underlying condition
that predisposes the subject to infection, or a positive result for human
immunodeficiency virus (HIV) infection confirmed by central laboratory at screening.
Subjects refusing HIV testing during the screening period will not be eligible for
study participation

10. Confirmed positive test for hepatitis B or hepatitis C

11. Any severe herpes infection at any time prior to Week 0 (Day 1)

12. Opportunistic infection requiring hospitalisation or intravenous antimicrobial
treatment within 3 years prior to randomization

13. History of cancer, apart from:

1. Squamous or basal cell carcinoma of the skin that has been successfully treated

2. Cervical cancer in situ that has been successfully treated



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Active Systemic Lupus Erythematosus

Intervention(s)

Biological: Anifrolumab

Drug: Placebo

Primary Outcome(s)

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index =4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules) [Time Frame: Week 52]

Secondary Outcome(s)

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of =4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules) [Time Frame: Week 24]

Number of Participants With Markedly Abnormal Laboratory Tests [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores [Time Frame: Baseline to Week 52]

Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Baseline to Week 52]

Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score [Time Frame: Baseline to Week 52]

Number of Participants Reporting One or More Adverse Events (AE) [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Number of Participants With Markedly Abnormal Vital Signs [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of =7.5 mg/Day in the Sub-group of Participants With Baseline OCS =10 mg/Day (Original Analysis With Restricted Medication Rules) [Time Frame: Week 52]

Annualized Flare Rate [Time Frame: Baseline to Week 52]

Number of Participants Reporting One or More Adverse Events of Special Interest (AESI) [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of =4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules) [Time Frame: Week 52]

Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules) [Time Frame: Week 52]

Number of Participants With a =50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score =10 (Original Analysis With Restricted Medication Rules) [Time Frame: Week 12]

Number of Participants With Markedly Abnormal Physical Examinations [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index [Time Frame: Baseline to End of Trial (Maximum of 60 weeks)]

Secondary ID(s)

D3461C00005

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

PRA Health Sciences

Results

• Results available: Yes
• Date Posted: 05/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02446912