Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects with Active Proliferative Lupus Nephritis - TULIP-LN1

Study identifier:D3461C00007

ClinicalTrials.gov identifier:NCT02547922

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official 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

Medical condition

Lupus Nephritis

Phase

Phase 2

Healthy volunteers

Study drug

Placebo

Sex

All

Actual Enrollment

147

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 04 Nov 2015

Primary Completion Date: 26 Nov 2019

Study Completion Date: 18 Jan 2021

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2021 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

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:
a. Positive antinuclear antibody (ANA) test (1:40 or higher) or
b. Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
c. 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

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
(a) Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or
(b) Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or
(c) IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose (500 mg every 2 weeks) or
(d) Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
(e) 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:
a. Squamous or basal cell carcinoma of the skin that has been successfully treated
b. 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:
(a) Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)
(b) Alanine transaminase (ALT) >2.5×ULN
(c) Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator’s judgement])
(d) Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects only)
(e) Neutrophil count <1x103/μL (or <1.0 GI/L)
(f) Platelet count <25x103/μL (or <25 GI/L)
(g) Haemoglobin <8 g/dL (or <80 g/L).

No locations available

Arms	Assigned Interventions
Experimental: Anifrolumab - Lower Dose Anifrolumab - Lower Dose	Biological/Vaccine: Anifrolumab Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Experimental: Anifrolumab - Higher Dose Anifrolumab - Higher Dose	Biological/Vaccine: Anifrolumab Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112
Placebo Comparator: Placebo Placebo IV Q4W plus SOC	Drug: Placebo Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112

Documents available

Protocol
Download
SAP
Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

AstraZeneca AB

AstraZeneca