A Study to Evaluate the Continuous Safety and Efficacy of Litifilimab (BIIB059) in Adults With Active Systemic Lupus Erythematosus



Sponsor:   Biogen


Sommario: 
      The primary objective of this study is to evaluate the long-term safety and tolerability of
      litifilimab in participants with active systemic lupus erythematosus (SLE).

      The secondary objectives of this study are to evaluate the long-term effect of litifilimab on
      disease activity in participants with SLE, to evaluate the long-term effect of litifilimab in
      participants with SLE in maintaining low disease activity, to evaluate the effect of
      litifilimab in participants with active SLE in preventing irreversible organ damage, to
      assess long-term use of oral corticosteroid (OCS) with participants receiving litifilimab
      treatment, to assess the impact of litifilimab on participant-reported Health-Related
      Quality-of-Life Questionnaire (HRQoL), symptoms, and impacts of SLE, to evaluate long-term
      effect of litifilimab on laboratory parameters, and to evaluate immunogenicity of
      litifilimab.
    




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 3




TRATTAMENTO

  
    
  
  • Litifilimab
  • Litifilimab-matching placebo
    • 






OBIETTIVO PRIMARIO


  
  • Misura: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
  • Tempo: Up to Week 180
  • Descrizione: An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that started or worsened in severity after the first dose of study treatment through 28 days after the last dose of study treatment or end of study (EOS) date, whichever comes earlier.
  • Misura: Number of Participants with Serious Adverse Events (SAEs)
  • Tempo: Up to Week 180
  • Descrizione: An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death (a life threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, and is a medically important event.




OBIETTIVO SECONDARIO


  
  • Misura: Percentage of Participants who Achieved an Systemic Lupus Erythematosus Responder Index (SRI)-4 Response
  • Tempo: Up to Week 180
  • Descrizione: SRI-4 is a composite endpoint defined as the following:
A reduction from baseline of ≥4 points in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score.
No new organ system affected, as defined by no new British Isles Lupus Activity Group-2004 (BILAG-2004 grade A) and no more than 1 new BILAG 2004 grade B versus previous visit.
No worsening from baseline in lupus disease activity as defined by <0.3-point increase on 3-point Physician's Global Assessment (PGA) visual analog scale (VAS).
No violation of protocol-specified medication rules
  • Misura: Percentage of Participants who Achieved a Joint-50 Response
  • Tempo: Up to Week 180
  • Descrizione: Joint-50 response is a 50% reduction in total active joint count from baseline. An active joint is defined as a joint with pain and signs of inflammation (e.g., tenderness, swelling or effusion). A 28-joint assessment will be performed to determine the active joint count, which is defined as the sum of tender and swollen joint counts.
  • Misura: Percentage of Participants who Achieved Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50, CLASI-70, and CLASI-90 Response
  • Tempo: Up to Week 180
  • Descrizione: CLASI score is used to evaluate lupus skin manifestations. The activity scale (CLASI-A) includes measurements of erythema, scale and hypertrophy, and mucous membrane disease. Each part of the body is listed separately, from the scalp to the feet, in addition to sections focusing on mucous membrane involvement and alopecia. Points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Scores for each area are assigned based on the most severe lesion within the area of interest. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-50 is 50% of improvement from baseline in CLASI-A. CLASI-70 is 70% of improvement from baseline in CLASI-A and CLASI-90 is 90% of improvement from baseline in CLASI-A.
  • Misura: Percentage of Participants who Achieved a British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) Response
  • Tempo: Up to Week 180
  • Descrizione: BICLA is a composite endpoint defined as the following:
BILAG-2004 improvement, defined as all of BILAG-2004 Grade A at Baseline improved to B, C, or D and all of BILAG-2004 Grade B at Baseline improved to C or D.
No BILAG-2004 worsening in other BILAG-2004 organ systems such that there are no new BILAG-2004 Grade A or greater than 1 new BILAG-2004 Grade B.
No worsening in the SLEDAI-2K total score compared to baseline.
No worsening from baseline in lupus disease activity defined by a <0.3-point increase on a 3-point PGA VAS.
No violation of protocol-specified medication rules.
  • Misura: Annualized Severe Safety of Estrogens in Systemic Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index Flare Index (SFI) Flare Rate
  • Tempo: Up to Week 156
  • Descrizione: A severe flare is defined as any of the following:
Change in SLEDAI instrument score to >12
New or worse: central nervous system SLE; vasculitis; nephritis; myositis; platelets <60,000/mL, or hemolytic anemia with hemoglobin <7 grams per deciliter (g/dL) or decrease in hemoglobin >3 g/dL and requiring: doubling prednisone dose, increase to >0.5 milligrams per kilograms per day (mg/kg/day) or hospitalization
Increase in prednisone dose to >0.5 mg/kg/day
New requirement for cyclophosphamide, azathioprine, methotrexate, or mycophenolate for SLE activity
Hospitalization for SLE activity
Increase in PGA score to >2.5
  • Misura: Percentage of Time Spent in Lupus Low Disease Activity State (LLDAS)
  • Tempo: Up to Week 180
  • Descrizione: LLDAS is a composite endpoint defined as the following:
i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.
"No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.
  • Misura: Percentage of Participants With Sustained LLDAS
  • Tempo: Up to Week 180
  • Descrizione: LLDAS is a composite endpoint defined as the following:
i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.
"No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.
  • Misura: Duration of Sustained LLDAS as Defined by the Number of Visits in LLDAS
  • Tempo: Up to Week 180
  • Descrizione: LLDAS is a composite endpoint defined as the following:
i. SLEDAI-2K score ≤ 4, with no activity in a major organ system (renal, central nervous system, cardiopulmonary, vasculitis, fever); and ii. No new features of lupus disease activity compared with the previous assessment; and iii. SELENA-SLEDAI PGA ≤ 1; and iv. Current prednisone (or equivalent) dose ≤ 7.5 mg/day; and v. Standard maintenance doses of immunosuppressive drugs and approved biological agents.
"No new features" is defined as any new SLEDAI-2K component that was not present at the previous assessment. The SELENA-SLEDAI PGA Scale ranges from 0-3, where 0 is no disease activity and 3 is maximum disease activity. "Standard maintenance doses" include drugs limited to those allowed per protocol.
  • Misura: Annual Change From Baseline Value From the Parent Phase 3 Studies in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) Score
  • Tempo: Up to Week 156
  • Descrizione: SDI score is used to assess the accumulated damage in participants with SLE. It assess 12 organ systems and records damage in participants with lupus, regardless of its cause. Damage could be due to previous disease activity, medication, or intercurrent illness (such as surgery or cancer). To distinguish between active inflammation and damage, an item must be present for at least 6 months. It is assumed that persistent inflammation (for at least 6 months) would result in tissue injury and hence damage. SDI is evaluated on a scale 0-47 with higher score indicating higher damage.
  • Misura: Cumulative Exposure to OCS Over Time
  • Tempo: Up to Week 156
  • Descrizione: 
  • Misura: Percentage of Participants With OCS ≤7.5 mg
  • Tempo: Up to Week 156
  • Descrizione: 
  • Misura: Percentage of Participants With OCS ≤5 mg
  • Tempo: Up to Week 156
  • Descrizione: 
  • Misura: Change From Baseline in Lupus-Specific Health-Related Quality-Of-Life (LupusQoL) Score
  • Tempo: Up to Week 156
  • Descrizione: The LupusQoL is a participant-reported, lupus-specific, HRQoL questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all the time. A LupusQoL score for each domain will be reported on a 0 to 100 scale, with greater values indicating better HRQoL.
  • Misura: Change From Baseline in Short Form Health Survey-36 (SF-36) (Acute Version) Score
  • Tempo: Up to Week 156
  • Descrizione: The SF-36 is a 36-item scale which assesses HRQoL in 8 domains: limitations in physical activities due to health problems, limitations in social activities due to physical or emotional problems, limitations in usual role activities due to physical health problems, bodily pain, general mental health (psychological distress and well-being), limitations in usual role activities due to emotional problems, vitality (energy and fatigue), general health perceptions. The SF-36 (Acute Version) form asks for participants to reply to questions (items) according to how they have felt over a specifically defined period of time. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36 where higher scores indicate best health. Scores on each item are summed and averaged (range: 0=worse health to 100=best possible health).
  • Misura: Change From Baseline in European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L)
  • Tempo: Up to Week 156
  • Descrizione: The EQ-5D is a standardized generic measure of health status developed by the European Quality of Life Group. This study uses the EQ-5D-3L version of the instrument. This instrument consists of 2 sections. The first section comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. All dimensions are measured on a 3-point scale, 1: No problems; 2: Some problems; 3: Extreme problems. The second section comprises the Visual Analogue Scale, which records the respondent's self-rated health on a vertical scale ranging from 0 to 100, lower scores indicate the worst possible health state.
  • Misura: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
  • Tempo: Up to Week 156
  • Descrizione: The FACIT-Fatigue is a participant-administered HRQoL questionnaire that evaluates participant's fatigue in 5 broad categories: physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns. The level of fatigue is measured by questions assessed on a 5-point scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The responses for each item are added to obtain a total score which ranges from 0 to 52, with a higher score indicating less fatigue.
  • Misura: Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score
  • Tempo: Up to Week 156
  • Descrizione: The PHQ-9 is a participant-administered HRQoL questionnaire to screen for the presence and severity of depression. The PHQ-9 is a participant-reported outcome (PRO) that is used to measure depression in adults. It contains 9 questions, with a 2 week recall period. The PHQ-9 yields an overall severity score that can range from 0 to 27 with the following severity scores: 0-4 = none; 5-9 = mild; 10-14 = moderate; 15-19 = moderate-to-severe; and 20-27 = severe.
  • Misura: Change From Baseline in Work Productivity and Activity Impairment (WPAI):Lupus Score
  • Tempo: Up to Week 156
  • Descrizione: WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. Each score ranges from 0 to 100, with higher numbers indicating greater impairment and less productivity.
  • Misura: Change from Baseline in Patient Global Assessment (PtGA) Score
  • Tempo: Up to Week 156
  • Descrizione: The PtGA is participant-administered, single-item question evaluating the impact of health and illness, with responses ranging from very poor to very well on a 100 mm VAS. The participant will consider the previous week when addressing this question.
  • Misura: Number of Participants with Clinically Relevant Abnormalities in Standard Laboratory Parameters
  • Tempo: Up to Week 180
  • Descrizione: Standard laboratory parameters will include hematology, blood chemistry, urinalysis, and coagulation.
  • Misura: Number of Participants with Clinically Relevant Abnormalities in Electrocardiogram (ECG) Results
  • Tempo: Up to Week 156
  • Descrizione: 
  • Misura: Number of Participants with Antibodies to Litifilimab
  • Tempo: Up to Week 180
  • Descrizione: 




CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    
        Key Inclusion Criteria:

          -  Participants who completed 1 of the 52-week of the double-blind placebo-controlled,
             parent Phase 3 studies (230LE303 (NCT04895241) and 230LE304 (NCT04961567)) on study
             treatments with either litifilimab or placebo to Week 48 and attended the last study
             assessment visit at Week 52

        Key Exclusion Criteria:

          -  Early parent Phase 3 studies treatment terminators (participants who discontinued
             study treatment before Week 52)

          -  Early parent Phase 3 studies terminators (participants who withdrew from study
             participation and did not complete the 52 week treatment period)

          -  Participants who developed moderate-to-severe worsening of organ-specific lupus
             manifestations that would require a change in antimalarials and/or immunosuppressive
             therapy (initiation of new treatment or increase in dose above the allowed maximum
             dose)

          -  Use of other investigational drugs or off-label drugs used to treat SLE, cutaneous
             lupus, or lupus nephritis during the parent Phase 3 studies

        NOTE: Other inclusion/exclusion criteria may apply.
      
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 18 Years

Età Massima: N/A






LUOGO


  
Istituto Clinico Humanitas
Rozzano, 20089
Ospedale M. Scarlato
Scafati, 84018
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, 25123
Azienda Socio Sanitaria Territoriale Gaetano Pini (Gaetano Pini-CTO)
Milano, 20122
Azienda Ospedaliera di Padova
Padova, 35100
Azienda Ospedaliero Universitaria Pisana
Pisa, 56100
Azienda Ospedaliera San Camillo Forlanini
Roma, 00151
Università Campus Bio-Medico di Roma
Roma, 00155
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
Roma, 00161