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

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2015-001442-29-HU
• Date of registration: 29/10/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• 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 - TULIP-LN1
• Date of first enrolment: 05/01/2016
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001442-29
• 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: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, France, Germany, Hungary, Italy, Korea, Republic of, Mexico, Peru, Poland, Russian Federation, Serbia, South Africa, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & 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 central laboratory; 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 mg/mg (113.17 mg/mmol), obtained on a 24-hour urine collection at both:
- The start of screening and
- Within 14 days prior to the expected date of randomisation. Without the results of the second (stratification) sample, subjects cannot be randomised.
5. Estimated glomerular filtration rate =35 mL/min/1.73 m2
6. Must not have active or untreated 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 administration of investigational product and prior to the first dose of sponsor-provided MMF
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 145
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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 mg/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 mg (cumulative dose) or
(c) IV cyclophosphamide >2 pulses of high dose
(=0.5 mg/m2) or >4 doses of low dose (500 mg every 2 weeks) or
(d) Average MMF >2.5 mg/day (or > 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
11. History of cancer, apart from:
a. Squamous or basal cell carcinoma of the skin
that has been successfully treated
b. High-grade squamous intraepithelial lesion (CIN III, CIS) treated with apparent success with curative therapy = 1 year prior to randomisation



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

Health Condition(s) or Problem(s) studied

Lupus Nephritis
MedDRA version: 20.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary 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
Current Sponsor code: Medi-546
Other descriptive name: ANIFROLUMAB
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 efficacy of anifrolumab plus standard of care (SOC) compared to placebo plus SOC in subjects with active proliferative lupus nephritis measured by the relative difference in change from baseline to Week 52 in 24-hour urine protein to creatinine ratio (UPCR)

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

Secondary Objective: To evaluate the effect of anifrolumab plus SOC compared to placebo plus SOC on:
- Proportion of subjects achieving Complete Renal Response (CRR) at Week 52
- Proportion of subjects achieving alternative CRR (aCRR) at Week 52. The difference between the CRR and the aCRR is the addition of a criterion regarding “inactive urine sediment”

Primary end point(s): The primary endpoint used to evaluate the effect of anifrolumab compared to placebo on LN
disease activity is the relative difference in change from baseline to Week 52 in the 24-hour
UPCR.

Secondary Outcome(s)

Secondary end point(s): Complete renal response
To evaluate the effect of anifrolumab compared to placebo on renal response in LN subjects,
the proportion of subjects achieving CRR at Week 52 will be used. A subject achieves CRR if
all of the following criteria are met:
• Estimated glomerular filtration rate (eGFR):
- =80 mL/min/1.73 m2, if baseline eGFR =90 mL/min/1.73 m2 or
- >85% of baseline eGFR, if baseline eGFR <90 mL/min/1.73 m2
• 24-hour UPCR <0.5 mg/mg
• No discontinuation of investigational product or use of restricted medication beyond
the protocol-allowed threshold before assessment.

Alternative Complete renal response
To evaluate the effect of anifrolumab compared to placebo on renal response in LN subjects
when urine sediment is considered in the definition, the proportion of subjects achieving
aCRR at Week 52 will be used. A subject achieves aCRR if all of the following criteria are
met:
• Estimated glomerular filtration rate (eGFR):
- =80 mL/min/1.73 m2, if baseline eGFR =90 mL/min/1.73 m2 or
- >85% of baseline eGFR, if baseline eGFR <90 mL/min/1.73 m2
• 24-hour UPCR <0.5 mg/mg
• Inactive urine sediment (defined as <10 RBC/hpf)

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

Secondary ID(s)

2015-001442-29-BE

D3461C00007

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 15/12/2015
Contact: