Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis



Sponsor:   AstraZeneca


Sommario: The purpose of this study is to evaluate the efficacy and safety of IV antifrolumab in
adult patients with Active Proliferative Lupus Nephritis




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 3




TRATTAMENTO

  
    
  
  • Anifrolumab
  • Placebo
    • 






OBIETTIVO PRIMARIO


  
  • Misura: Difference in proportion of participants with CRR (Complete Renal Response) in anifrolumab group compared with placebo group
  • Tempo: Week 52
  • Descrizione: CRR is defined as:

  -  UPCR ≤ 0.5 mg/mg

  -  eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%




OBIETTIVO SECONDARIO


  
  • Misura: Difference in proportion of participants achieving sustained OCS reduction in anifrolumab group compared with placebo group.
  • Tempo: from Week 24 through Week 52
  • Descrizione: Sustained OCS reduction
  • Misura: Hazard Ratio (HR) of achieving sustained CRR in anifrolumab compared with placebo group
  • Tempo: baseline through Week 52
  • Descrizione: 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.
  • Misura: Difference in the mean standardized AUC for UPCR between anifrolumab and placebo participants
  • Tempo: baseline through Week 52
  • Descrizione: Proteinuria as measured by the cumulative UPCR
  • Misura: 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
  • Tempo: baseline through Week 52, baseline through Week 104
  • Descrizione: 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:

  1. ESKD,

  2. doubling of serum creatinine,

  3. renal worsening as evidenced by increased proteinuria and/or renal function
     impairment, or 4) renal disease treatment failure or death
  • Misura: Difference in proportion of participants achieving aCRR (Alternative Complete Renal Response)
  • Tempo: Week 52
  • Descrizione: 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%.
  • Misura: Difference in the proportion of participants achieving CRR with sustained OCS reduction
  • Tempo: Week 52
  • Descrizione: CRR with sustained OCS reduction
  • Misura: Difference in the proportion of participants achieving CRR
  • Tempo: Week 24
  • Descrizione: Early onset of CRR
  • Misura: HR of achieving sustained CRR in anifrolumab compared with placebo
  • Tempo: baseline through Week 104
  • Descrizione: Time to sustained CRR through the time frame period
  • Misura: HR of achieving 50% reduction in UPCR in anifrolumab compared to placebo group
  • Tempo: baseline through Week 52
  • Descrizione: The endpoint for deriving the summary measure is time from the first dose of study
intervention to achieving 50% reduction in UPCR
  • Misura: Difference in mean UPCR between the anifrolumab and placebo group
  • Tempo: Week 52
  • Descrizione: Proteinuria as measured by UPCR
  • Misura: PRR (Partial Renal Response)
  • Tempo: Week 52
  • Descrizione: PRR defined as:

UPCR:

  -  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%
  • Misura: Difference in change from baseline in extra-renal SLEDAI-2K total score
  • Tempo: baseline through Week 104
  • Descrizione: The extra-renal SLEDAI-2K score is obtained by summing the SLEDAI-2K items without
including the items within the renal system organ.
  • Misura: 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
  • Tempo: Week 52
  • Descrizione: To evaluate patient-reported HRQOL and health status




CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    Inclusion Criteria:

  1. Active proliferative LN Class III or IV either with or without the presence of Class
     V according to the 2003 ISN/RPS classification

  2. Renal biopsy obtained within 6 months prior to signing the ICF or during Screening
     Period.

  3. Urine protein to creatinine ratio > 1 mg/mg (113.17 mg/mmol)

  4. eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology
     Collaboration formula).

  5. Fulfills updated 2019 EULAR/ACR SLE classification criteria.

  6. No signs of symptoms of active TB prior to or during screening or no treatment for
     latent TB

Exclusion Criteria:

  1. A diagnosis of pure Class V LN based on the renal biopsy obtained within 6 months
     prior to signing the ICF or during Screening.

  2. 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).

  3. Evidence of hepatitis C or active hepatitis B.

  4. Any history of cancer except sucessfully cured skin squamos or basal skin carcinoma
     and cervical cancer in situ.

  5. 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.

  6. Previous receipt of >◦2 investigation treatments (other than anifrolumab) for LN or
     SLE since time of diagnosis and through the ICF.

  7. Known intolerance to ≤ 1.0 g/day of MMF.

  8. Any history of severe COVID-19 infection.
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 18 Years

Età Massima: 70 Years






LUOGO


  
Research Site
Ancona, 60126
Research Site
Bologna, 40138
Research Site
Brescia, 25123
Research Site
Cona, 44124
Research Site
Eboli, 84025
Research Site
Monza, 20900
Research Site
Padova, 35128
Research Site
Roma, 00152
Research Site
Roma, 00161
      


    
REFERENTE PER INFORMAZIONI

    

      AstraZeneca Clinical Study Information Center
      1-877-240-9479
      information.center@astrazeneca.com