A study to evaluate the efficacy and safety of two doses of Anifrolumab compared to placebo in adult patients with Active Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2014-004633-96-GB
• Date of registration: 08/05/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A study to evaluate the efficacy and safety of two doses of Anifrolumab compared to placebo in adult patients 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: 16/07/2015
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004633-96
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

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: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged 18 through 70 years at the time of screening
2. Completion of all screening procedures needed to determine subject
eligibility and stratification within 30 days after signing the Informed Consent Form (ICF)
3. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according
to the ACR 1982 revised criteria =24 weeks prior to signing the ICF
4. Currently receiving at least 1 of the following:
(a) Where prednisone is the single standard of care medication, 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.
(b) Where prednisone is not the single standard of care medication, 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.
(c) 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
5. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for
SLE, at least 1 of which must be:
(a) Positive antinuclear antibody (ANA) test at screening by
immunofluorescent assay (IFA) at the central laboratory with titre =
1:80; OR
(b) Anti-dsDNA antibodies at screening elevated to above normal
(including indeterminate), as per the central laboratory; OR
(c) Anti-Smith (anti-Sm) antibody at screening elevated to above normal
as per the central laboratory
6. 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.
7. Meets all of the following TB criteria:
(i) No history of active TB prior to any Screening visit
(ii) No history of latent TB prior to initial Screening visit, with the
exception of latent TB with documented completion of appropriate
treatment. Subjects with no history of latent TB prior to the initial
Screening visit, but who are diagnose
Exclusion criteria:
1. Receipt of any of the following:
(a) Where prednisone is the single standard of care medication, any new oral prednisone therapy (or equivalent) any time in the 8 weeks prior to Day 1, OR any change in/discontinuation of current oral prednisone dose
(or equivalent) anytime within the 2 weeks prior to randomisation
(b) Where prednisone is not the single standard of care medication:
(i) Any addition of a new oral prednisone therapy (or equivalent) any
time from 2 weeks prior to signing of the informed consent form through Day 1, OR any change in/discontinuation of current oral prednisone dose
(or equivalent) anytime within 2 weeks prior randomisation
(ii) Any addition of a new dose of any of the following anytime in the 12
weeks prior to signing of the informed consent through Day 1, or change in/discontinuation of current dose anytime in the 8 weeks prior to signing of the informed consent through Day 1: azathioprine; any
antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine);
mycophenolate mofetil/mycophenolic acid; oral, SC, or intramuscular
methotrexate; mizoribine
2. Receipt of any of the following:
(a) Azathioprine >200 mg/day
(b) Mycophenolate mofetil >2 g/day or mycophenolic acid >1.44 g/day
(c) Oral, SC, or intramuscular methotrexate >25 mg/week
(d) Mizoribine >150 mg/day
(e) Any change in route of administration of oral, SC, or intramuscular
methotrexate anytime within the 8 weeks prior to signing of the
informed consent through Day 1
3. 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
4. Receipt of epratuzumab or tabalumab =26 weeks prior to signing the
ICF, or belimumab <12 weeks prior to signing the ICF
5. Receipt of any of the following:
(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6
weeks prior to Day 1
6. History of, or current diagnosis of, a clinically significant non SLErelated vasculitis syndrome.
7. Active severe or unstable neuropsychiatric SLE
8. Active severe SLE-driven renal disease
9. Diagnosis (within 1 year of signing the ICF) of mixed connective
tissue disease or any history of overlap syndromes of SLE and SSc.
10. History of, or current, inflammatory joint or skin disease other than
SLE
11. History of any non-SLE disease that has required treatment with oral or parentertal corticosteroids for more than 2 weeks within the 24 weeksprior to signing the ICF
12. 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Anifrolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Anifrolumab
CAS Number: 1326232-46-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Anifrolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Anifrolumab
CAS Number: 1326232-46-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: - To evaluate the effect of anifrolumab 300 mg compared to placebo on
disease activity as measured by the difference in the proportion of subjects who achieve an SLE Responder Index of =4 (SRI[4]) at Week 52

Primary end point(s): The primary endpoint is the difference in proportions of subjects
achieving Systemic Lupus Erythematosus Responder Index SRI(4) at
Week 52 comparing anifrolumab to placebo.

Secondary Objective: 1. To evaluate the effect of anifrolumab 300mg compared to placebo on:
a. The proportion of subjects with SRI(4) at Week 52 in the IFN testhigh
sub-group
b. The proportion of subjects who achieve an OCS dose =7.5 mg/day at
Week 40, which is maintained through Week 52 in the sub-group of
subjects with baseline OCS =10 mg/day
c. The proportion of subjects with a =50% reduction in CLASI activity
score at Week 12 in the sub-group of subjects with baseline CLASI
activity score =10
d. The proportion of subjects with SRI(4) at Week 24
e. The annualised flare rate through 52 weeks
2. To evaluate the effect of anifrolumab 150 mg compared to placebo on disease activity as measured by the difference in the proportion of subjects who achieve SRI(4) at Week 52
3. To evaluate the safety and tolerability of anifrolumab

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Secondary end point(s): 1a. The composite endpoint SRI4 will be the measure of this objective.
1b. Maintained OCS reduction defined by the following criteria:
- Achieve an OCS dose of =7.5 mg/day prednisone or equivalent by
Week 40 and
- Maintain an OCS dose =7.5 mg/day prednisone or equivalent from
Week 40 to Week 52 and
- No discontinuation of investigational product or use of restricted
medications beyond the protocol-allowed threshold before assessment
1c. 50% reduction in CLASI activity score compared to baseline defined
by the following criteria:
- Achieve =50% reduction of CLASI activity score at Week 12 compared
to baseline and
- No discontinuation of investigational product or use of restricted
medications beyond the protocol-allowed threshold before assessment
1d. The composite endpoint SRI4 will be the measure of this objective
1e. Annualised flare rate with flare defined as either 1 or more new
BILAG-2004 A or 2 or more new BILAG-2004 B items compared to the
previous visit
2. The composite endpoint SRI4 will be the measure of this objective
3. The following safety data will be collected: vital signs, physical
examination, 12-lead ECG, haematology, clinical chemistry, urinalysis, CSSRS, PHQ-8, SLEDAI 2K Flare Index, and reported AEs

Timepoint(s) of evaluation of this end point: 1a. - Week 52
1b. - Week 52
1c. - Week 12
1d. - Week 24
1e. - Weeks 0- 52
2. - Week 52
3. - Weeks 0-52

Secondary ID(s)

D3461C00005

NCT02446912

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 16/07/2015
Contact:

Results

• Results available: Yes
• Date Posted: 18/12/2019
• Date Completed: 23/08/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004633-96/results