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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02547922




Registration number
NCT02547922
Ethics application status
Date submitted
31/08/2015
Date registered
14/09/2015
Date last updated
14/04/2020

Titles & IDs
Public title
Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis
Scientific title
A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Proliferative Lupus Nephritis
Secondary ID [1] 0 0
D3461C00007
Universal Trial Number (UTN)
Trial acronym
TULIP-LN1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Anifrolumab
Treatment: Drugs - Placebo

Experimental: Anifrolumab - Lower Dose - Anifrolumab - Lower Dose

Experimental: Anifrolumab - Higher Dose - Anifrolumab - Higher Dose

Placebo Comparator: Placebo - Placebo IV Q4W plus SOC


Other interventions: Anifrolumab
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Treatment: Drugs: Placebo
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relative difference in change from baseline in 24-hour urine protein to creatinine ratio (UPCR) - To evaluate the efficacy of anifrolumab plus SOC (combination of MMF and corticosteroids) compared with placebo plus SOC in subjects with active proliferative LN.
Timepoint [1] 0 0
From Week 1 (baseline) up to Week 52
Secondary outcome [1] 0 0
Difference in the proportion of subjects achieving the composite endpoint Complete Renal Response (CRR) - CRR is defined as meeting all of the following:
Estimated glomerular filtration rate (eGFR) is - =60 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of =20%
24-hour UPCR=0.7 mg/mg
No discontinuation of investigational product (IP) or use of restricted medication beyond the protocol-allowed threshold before assessment.
eGFR is based on Modification of Diet in Renal Disease (MDRD) formula.
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
No of subjects with adverse events (AEs) - To assess AEs (non-serious, serious and special interest) as variables of safety and tolerability of anifrolimab.
Timepoint [2] 0 0
From baseline up to Week 52
Secondary outcome [3] 0 0
Columbia-Suicide Severity Rating Scale (C-SSRS) - The C-SSRS will assess suicidal ideation and behavior on a graded scale from 1 to 5. 1 indicates as low suicidal and 5 as high suicidal behavior.
Timepoint [3] 0 0
From baseline up to Week 52
Secondary outcome [4] 0 0
Personal Health Questionnaire Depression Scale-8 - The PHQ-8 consists of eight of the nine criteria on which the Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV diagnosis of depressive disorders is based. It assesses symptoms of depression over the last 2 weeks.
Timepoint [4] 0 0
At week 0, week 12, week 24, week 36, and week 52.
Secondary outcome [5] 0 0
Extra-renal flares using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) based Flare Assessment Instrument - Flare will be defined as any one criterion present in either the Mild/Moderate Flare and/or Severe Flare categories. New or worsened manifestation should only be reported for manifestations of SLE. The SLEDAI-2K score range is 0 to 105 points with 0 indicating inactive disease.
Timepoint [5] 0 0
From baseline up to week 52
Secondary outcome [6] 0 0
Number of subjects with abnormal findings in vital signs - To assess any clinically significant abnormal vital signs findings as variable of safety and tolerability after administration of anifrolumab.
Timepoint [6] 0 0
From baseline up to Week 52
Secondary outcome [7] 0 0
Number of subjects with abnormal findings in laboratory evaluations - To assess any clinically significant abnormal laboratory tests findings as variable of safety and tolerability after administration of anifrolumab.
Timepoint [7] 0 0
From baseline up to Week 52

Eligibility
Key inclusion criteria
Main

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

2. Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria
for SLE, at least one of which must be:

1. Positive antinuclear antibody (ANA) test (1:40 or higher) or

2. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive
results), as per the centrallaboratory; or

3. Anti-Smith antibody at screening elevated to above normal (ie, positive or
equivocal results) as per the central laboratory

3. Class III (±Class V) or Class IV (±Class V) LN according to the World Health
Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained
within 12 weeks prior to signing the ICF or during the screening period:

4. Urine protein to creatinine ratio >1 gm/gm (113.17 mg/mmol), obtained on a 24-hour
urine collection at screening

5. Estimated glomerular filtration rate =35 mL/min/1.73 m2

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

7. Women of childbearing potential must have a negative serum beta-hCG test at screening
and negative urine pregnancy test prior to the first dose of sponsor-provided MMF.

Main
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receipt of any investigational product (small molecule or biologic) or commercially
available biologic agent within four weeks or 5 half lives prior to signing of the
ICF, whichever is greater

2. Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing
ICF or during the screening period

3. Known intolerance to =1.0 gm/day of MMF

4. History of dialysis within 12 months prior to signing the ICF or expected need for
renal replacement therapy (dialysis or renal transplant) within a 6 month period after
enrolment

5. Subjects, who at the time of signing the ICF, received any of the following
immunosuppressive therapies after their qualifying biopsy

1. Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or

2. Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or

3. IV cyclophosphamide >2 pulses of high-dose (=0.5 gm/m2) or >4 doses of low dose
(500 mg every 2 weeks) or

4. Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for
more than 8 weeks or

5. Tacrolimus >4 mg/day for more than 8 weeks

6. Major surgery within 8 weeks before signing the ICF or major surgery planned during
the study period

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

8. Confirmed positive test for hepatitis B or hepatitis C

9. Any severe herpes infection at any time prior to randomization

10. Opportunistic infection requiring hospitalisation or parenteral antimicrobial
treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is
not an exclusionreason).

11. 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

12. Concurrent enrolment in another clinical study with an IP within 4 weeks prior to ICF
signing or within 5 half-lives of the IP used in that clinical study, whichever is
longer.

13. During screening (within 30 days before Day 1 [Week 0 visit]), any of the following:

1. Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)

2. Alanine transaminase (ALT) >2.5×ULN

3. Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator's
judgement])

4. Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects
only)

5. Neutrophil count <1x103/µL (or <1.0 GI/L)

6. Platelet count <25x103/µL (or <25 GI/L)

7. Haemoglobin <8 g/dL (or <80 g/L).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Clayton
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
VIC 3168 - Clayton
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Cordoba
Country [13] 0 0
Argentina
State/province [13] 0 0
Rosario
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Belgium
State/province [17] 0 0
Liege
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux Cedex
Country [19] 0 0
France
State/province [19] 0 0
Marseille
Country [20] 0 0
France
State/province [20] 0 0
Paris Cedex 14
Country [21] 0 0
France
State/province [21] 0 0
Strasbourg
Country [22] 0 0
France
State/province [22] 0 0
Toulouse
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Germany
State/province [24] 0 0
Kiel
Country [25] 0 0
Hungary
State/province [25] 0 0
Budapest
Country [26] 0 0
Hungary
State/province [26] 0 0
Debrecen
Country [27] 0 0
Hungary
State/province [27] 0 0
Kaposvár
Country [28] 0 0
Hungary
State/province [28] 0 0
Szeged
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Padova
Country [31] 0 0
Italy
State/province [31] 0 0
Pisa
Country [32] 0 0
Italy
State/province [32] 0 0
Reggio Emilia
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Gwangju
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Suwon-si
Country [36] 0 0
Mexico
State/province [36] 0 0
Chihuahua
Country [37] 0 0
Mexico
State/province [37] 0 0
Guadalajara
Country [38] 0 0
Mexico
State/province [38] 0 0
Mexico
Country [39] 0 0
Mexico
State/province [39] 0 0
San Luis Potosí
Country [40] 0 0
Peru
State/province [40] 0 0
Arequipa
Country [41] 0 0
Peru
State/province [41] 0 0
Lima
Country [42] 0 0
Poland
State/province [42] 0 0
Krakow
Country [43] 0 0
Poland
State/province [43] 0 0
Warszawa
Country [44] 0 0
Poland
State/province [44] 0 0
Lódz
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Orenburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saint Petersburg
Country [47] 0 0
Serbia
State/province [47] 0 0
Belgrade
Country [48] 0 0
Serbia
State/province [48] 0 0
Nis
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Taiwan
State/province [50] 0 0
Changhua City
Country [51] 0 0
Taiwan
State/province [51] 0 0
Kaohsiung
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taichung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Taipei
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taoyuan City
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Parexel
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment
regimen of two doses of anifrolumab versus placebo in adult subjects with active
proliferative lupus nephritis (LN).
Trial website
https://clinicaltrials.gov/show/NCT02547922
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AstraZeneca AB
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications