Safety and Efficacy of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Proliferative Lupus Nephritis (TULIP-LN1)
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| ClinicalTrials.gov Identifier: NCT02547922 |
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Recruitment Status :
Completed
First Posted : September 14, 2015
Results First Posted : November 24, 2021
Last Update Posted : November 24, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lupus Nephritis | Biological: Anifrolumab Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 147 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | November 4, 2015 |
| Actual Primary Completion Date : | November 26, 2019 |
| Actual Study Completion Date : | January 18, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Anifrolumab - Lower Dose
Anifrolumab - Lower Dose
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Biological: Anifrolumab
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112 |
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Experimental: Anifrolumab - Higher Dose
Anifrolumab - Higher Dose
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Biological: Anifrolumab
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112 |
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Placebo Comparator: Placebo
Placebo IV Q4W plus SOC
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Drug: Placebo
Administration every 4 week from Week 0 to Week 100 in addition to SOC which will continue until Week 112 |
- Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR) [ Time Frame: From Week 1 (Baseline) up to Week 52 ]
To evaluate the efficacy of anifrolumab plus SOC (combination of mycophenolate mofetil and corticosteroids) compared with placebo plus SOC in subjects with active proliferative lupus nephritis (LN).
Geometric mean ratio of 24-hour UPCR at week 52 over baseline. Values <1 indicate improvement from baseline.
- Proportion of Subjects Achieving the Composite Endpoint Complete Renal Response (CRR) [ Time Frame: Week 52 ]
CRR was defined as meeting all of the following:
- Estimated glomerular filtration rate (eGFR) is ≥60 mL/min/1.73 m^2 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 was based on Modification of Diet in Renal Disease (MDRD) formula. Subjects treated with restricted medication beyond the protocol allowed threshold, or discontinuing study treatment for other reasons, were regarded as non-responders.
- Number of Subjects With Adverse Events [ Time Frame: From screening (Day-30 to -1) period until the follow-up period (Week 112) ]
To assess AEs (non-serious, serious and adverse event of special interest (AESI)) as variables of safety and tolerability of anifrolimab.
The AESIs are serious infections, including non-opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, TB (including latent TB), influenza, vasculitis (non-SLE), and MACE (including stroke, acute coronary syndrome, myocardial infarction, or cardiovascular death).
Study period: During treatment and follow-up data are presented.
- Number of Subjects With Suicidal Ideation and Behavior and Suicide Attempts Via Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline, treatment and follow up (an average of 60 weeks) ]The C-SSRS was used to assess the suicidal ideation and behavior and suicide attempts on a graded scale from 1 to 5. 1 indicates as low suicidal and 5 as high suicidal behavior.
- Total Score of Personal Health Questionnaire Depression Scale-8 (PHQD-8) [ Time Frame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 60 ]PHQ-8 is a 8-item self-report scale, all items are rated on a score of 0-3, for a total range of 0-24. PHQ-8 assesses symptoms of depression over the previous 2 weeks. Higher scores indicate more depressive symptoms.
- Extra-renal Flares Using Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI 2K) Based Flare Assessment Instrument [ Time Frame: From baseline up to week 112 ]
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 with higher scores representing increased disease activity.
Mild/ Moderate flare defined as change in non-renal components of the SLEDAI-2K instrument score of ≥3 but <7 points compared to previous visit. Severe Flare defined as change in non-renal components of the SLEDAI-2K instrument score by ≥7 points compared to previous visit.
The flare rate per subject year is defined as the number of subjects with a respective flare divided by the sum of exposure time in days for all subjects in the analysis set multiplied by 365.25.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Main Inclusion Criteria:
- Age 18 through 70 years at the time of screening
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Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be:
- Positive antinuclear antibody (ANA) test (1:40 or higher) or
- Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
- Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory
- 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:
- Urine protein to creatinine ratio >1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening
- Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
- Must not have active or latent TB on either chest radiograph or by Quantiferon gold test
- 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:
- 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
- Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period
- Known intolerance to ≤1.0 gm/day of MMF
- 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
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Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy
- Oral corticosteroids >0.5 mg/kg/day for more than 8 weeks or
- Oral or IV pulse methylprednisolone >3.0 gm (cumulative dose) or
- IV cyclophosphamide >2 pulses of high-dose (≥0.5 gm/m2) or >4 doses of low dose (500 mg every 2 weeks) or
- Average MMF >2.5 gm/day (>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
- Tacrolimus >4 mg/day for more than 8 weeks
- Major surgery within 8 weeks before signing the ICF or major surgery planned during the study period
- 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
- Confirmed positive test for hepatitis B or hepatitis C
- Any severe herpes infection at any time prior to randomization
- Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years prior to randomization (vaginal, oral and skin candidiasis is not an exclusionreason).
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History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin that has been successfully treated
- Cervical cancer in situ that has been successfully treated
- 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.
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During screening (within 30 days before Day 1 [Week 0 visit]), any of the following:
- Aspartate transaminase (AST) >2.5×upper limit of normal (ULN)
- Alanine transaminase (ALT) >2.5×ULN
- Total bilirubin >ULN (unless due to Gilbert's syndrome [based on Investigator's judgement])
- Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects only)
- Neutrophil count <1x103/μL (or <1.0 GI/L)
- Platelet count <25x103/μL (or <25 GI/L)
- Haemoglobin <8 g/dL (or <80 g/L).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02547922
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| Study Director: | AstraZeneca AB | AstraZeneca |
Documents provided by AstraZeneca:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT02547922 |
| Other Study ID Numbers: |
D3461C00007 |
| First Posted: | September 14, 2015 Key Record Dates |
| Results First Posted: | November 24, 2021 |
| Last Update Posted: | November 24, 2021 |
| Last Verified: | October 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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lupus, nephritis, randomized, placebo, anifrolumab, safety, efficacy, adult |
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Nephritis Lupus Nephritis Kidney Diseases Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases |
Male Urogenital Diseases Glomerulonephritis Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |