Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis (IRIS)
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|ClinicalTrials.gov Identifier: NCT05138133|
Recruitment Status : Recruiting
First Posted : November 30, 2021
Last Update Posted : February 10, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Lupus Nephritis||Drug: Anifrolumab Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||360 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double Blind (Participant, Care Provider and Investigator)|
|Official Title:||A Multicentre Randomized Double-Blind Placebo Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis|
|Actual Study Start Date :||February 15, 2022|
|Estimated Primary Completion Date :||April 2, 2026|
|Estimated Study Completion Date :||July 8, 2027|
Solution for intravenous infusion
Anifrolumab intravenous infusion (IV)
Other Name: Medi-546
Placebo Comparator: Placebo
Solution for intravenous infusion
Placebo intravenous infusion (IV)
- Difference in proportion of participants with CRR (Complete Renal Response) in anifrolumab group compared with placebo group [ Time Frame: Week 52 ]
CRR is defined as:
- UPCR ≤ 0.5 mg/mg
- eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%
- Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group. [ Time Frame: from Week 24 through Week 52 ]Sustained OCS reduction
- Hazard Ratio (HR) of achieving sustained CRR in anifrolumab compared with placebo group [ Time Frame: baseline through Week 52 ]The endpoint for deriving the summary measure is time to sustained CRR, defined as time to achieving CRR that is sustained from that time point through the end of the time frame period.
- Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants [ Time Frame: baseline through Week 52 ]Proteinuria as measured by the cumulative UPCR
- HR to summarize the difference in the risk of hazard of renal-related event or death at any given time between anifrolumab and placebo participants [ Time Frame: baseline through Week 52, baseline through Week 104 ]
The endpoint for deriving the summary measure is time to onset of renal-related event or death.
Time to onset of renal event as defined as any of the following:
- doubling of serum creatinine,
- renal worsening as evidenced by increased proteinuria and/or renal function impairment, or 4) renal disease treatment failure or death
- Difference in proportion of participants achieving aCRR (Alternative Complete Renal Response) [ Time Frame: Week 52 ]
aCRR is defined as:
- UPCR ≤ 0.5 mg/mg;
- eGFR ≥ 90 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of ≥ 10%.
- Difference in the proportion of participants achieving CRR with sustained OCS reduction [ Time Frame: Week 52 ]CRR with sustained OCS reduction
- Difference in the proportion of participants achieving CRR [ Time Frame: Week 24 ]Early onset of CRR
- HR of achieving sustained CRR in anifrolumab compared with placebo [ Time Frame: baseline through Week 104 ]Time to sustained CRR through the time frame period
- HR of achieving 50% reduction in UPCR in anifrolumab compared to placebo group [ Time Frame: baseline through Week 52 ]The endpoint for deriving the summary measure is time from the first dose of study intervention to achieving 50% reduction in UPCR
- Difference in mean UPCR between the anifrolumab and placebo group [ Time Frame: Week 52 ]Proteinuria as measured by UPCR
- PRR (Partial Renal Response) [ Time Frame: Week 52 ]
PRR defined as:
- For participants with a baseline UPCR ≤3 mg/mg: <1.0 mg/mgb eGFR:
≥ 60 mL/min/1.73 m2 or no confirmed decrease of eGFR from baseline of ≥ 20%
- Difference in change from baseline in extra-renal SLEDAI-2K total score [ Time Frame: baseline through Week 104 ]The extra-renal SLEDAI-2K score is obtained by summing the SLEDAI-2K items without including the items within the renal system organ.
- Difference in mean change from baseline in domains and component scores of Short Form-36 Version 2 (SF-36v2) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) total score [ Time Frame: Week 52 ]To evaluate patient-reported HRQOL and health status
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|
- Active proliferative LN Class III or IV either with or without the presence of Class V according to the 2003 ISN/RPS classification
- Renal biopsy obtained within 6 months prior to signing the ICF or during Screening Period.
- Urine protein to creatinine ratio > 1 mg/mg (113.17 mg/mmol)
- eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula).
- Fulfills updated 2019 EULAR/ACR SLE classification criteria.
- No signs of symptoms of active TB prior to or during screening or no treatment for latent TB
- A diagnosis of pure Class V LN based on the renal biopsy obtained within 6 months prior to signing the ICF or during Screening.
- Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV confirmed by the central lab at Screening - an HIV test must be performed during Screening, and the result should be available prior to Week 0 (Day 1).
- Evidence of hepatitis C or active hepatitis B.
- Any history of cancer except sucessfully cured skin squamos or basal skin carcinoma and cervical cancer in situ.
- Receipt of the following for the current LN flare (ie, since the qualifying renal biopsy): IV cyclophosphamide > 2 pulses of high-dose (≥ 0.5 g/m2) or > 4 doses of low dose (500 mg every 2 weeks) or Average MMF > 2.5 g/day (or > 1800 mg/day of enteric coated mycophenolate sodium) for more than 8 weeks or Tacrolimus > 4 mg/day for more than 8 weeks; Cyclosporine for more than 8 weeks or during last 8 weeks prior to signing the ICF; Voclosporin for more than 8 weeks or during last 8 weeks prior to signing the ICF; Belimumab for more than 12 weeks or during last 12 weeks prior the ICF.
- Previous receipt of >◦2 investigation treatments (other than anifrolumab) for LN or SLE since time of diagnosis and through the ICF.
- Known intolerance to ≤ 1.0 g/day of MMF.
- Any history of severe COVID-19 infection.
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): NCT05138133
|Contact: AstraZeneca Clinical Study Information Centeremail@example.com|
|Other Study ID Numbers:||
2021-002862-42 ( EudraCT Number )
|First Posted:||November 30, 2021 Key Record Dates|
|Last Update Posted:||February 10, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
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: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean that all requests will be shared.
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. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.|
|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. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Lupus Nephritis, anifrolumab, Systemic Lupus Erythematosus, intravenous
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Immune System Diseases