A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus

Sponsor: UCB Biopharma SRL

Sommario: The purpose of this study is to evaluate the ability of dapirolizumab pegol (DZP) as an add-on treatment to standard of care (SOC) medication to achieve clinically relevant long term improvement of moderate to severe disease activity.


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO

  • DZP
  • Placebo

OBIETTIVO PRIMARIO

  • Misura: Achievement of BICLA response at Week 48
  • Tempo: Week 48
  • Descrizione: A study participant is considered to be a BILAG 2004-based Composite Lupus Assessment (BICLA) responder if all of the following is fulfilled: British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B.); and No worsening in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and No worsening in the Physician's Global Assessment of Disease (PGA) compared to Baseline Visit defined as ≤10mm increase on a 100mm visual analog scale Escape treatment intervention as indicated by Investigator until the assessment time point will be defined as an intercurrent event for the primary endpoint leading to non-response from the day after the event onward.

OBIETTIVO SECONDARIO

  • Misura: Achievement of BICLA response at Week 24
  • Tempo: Week 24
  • Descrizione: A study participant is considered to be a BICLA responder if all of the following is fulfilled: BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B.); and No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and No worsening in the PGA compared to Baseline Visit defined as ≤10mm increase on a 100mm visual analog scale Escape treatment intervention as indicated by Investigator until the assessment time point will be defined as an intercurrent event for the primary endpoint leading to non-response from the day after the event onward.
  • Misura: Achievement of BICLA response at Week 12
  • Tempo: Week 12
  • Descrizione: A study participant is considered to be a BICLA responder if all of the following is fulfilled: BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B.); and No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and No worsening in the PGA compared to Baseline Visit defined as ≤10mm increase on a 100mm visual analog scale Escape treatment intervention as indicated by Investigator until the assessment time point will be defined as an intercurrent event for the primary endpoint leading to non-response from the day after the event onward.
  • Misura: Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 48
  • Tempo: During Treatment Period up to Week 48
  • Descrizione: BILAG severe flare is defined as a British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index (Yee et al, 2010).
  • Misura: Achievement of LLDAS in ≥50% of post-Baseline visits through Week 48
  • Tempo: During Treatment Period up to Week 48
  • Descrizione: Low lupus disease activity state (LLDAS) is defined as: No significant disease activity as per SLEDAI-2K and BILAG 2004 (SLEDAI-2K score ≤4 with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) No new and/or worsening disease activity defined as no SLEDAI-2K component documented as present that was not documented present at previous visit PGA ≤33mm Prednisone equivalent systemic dose for systemic lupus erythematosus (SLE) indication ≤7.5mg per day Stable standard maintenance doses of immunosuppressive drugs as allowed by protocol
  • Misura: Change from Baseline in SLEDAI-2K at Week 48
  • Tempo: From Baseline (Day 1) to Week 48
  • Descrizione: The SLEDAI-2K Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K; 30 days) measures disease activity. It is a global index and includes 24 clinical symptoms and laboratory variables that are weighted by the type of manifestation, but not by severity or dynamic of the individual item. The total score falls between 0 and 105, with higher scores representing increased disease activity.
  • Misura: Achievement of BILAG improvement without worsening at Week 48
  • Tempo: Week 48
  • Descrizione: BILAG 2004 improvement without worsening can be defined as A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B.
  • Misura: Change from Baseline in PGA at Week 48
  • Tempo: From Baseline (Day 1) to Week 48
  • Descrizione: Physician's Global Assessment of Disease (PGA) The Investigator will rate the overall status of the study participant.
  • Misura: Achievement of SRI4 response at Week 48
  • Tempo: Week 48
  • Descrizione: The Systemic Lupus Erythematosus Responder Index (SRI)-4 define responders as (ie, all criteria must be met): Reduction in SLEDAI-2K score of ≥4 No shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline No worsening in the PGA compared to study entry defined as ≤10mm increase on a 100mm visual analog scale
  • Misura: Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48
  • Tempo: During Treatment Period up to Week 48
  • Descrizione: BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index (Yee et al, 2010). BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items that are new or worse and are qualifying for the Grade B in any system (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade B will be according to the supplementary information for the numerical scoring of the BILAG- 2004 index (Yee et al, 2010)
  • Misura: Time to severe BILAG Flare through Week 48
  • Tempo: During Treatment Period up to Week 48
  • Descrizione: BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index (Yee et al, 2010).
  • Misura: Time to moderate/severe BILAG flare through Week 48
  • Tempo: During Treatment Period up to Week 48
  • Descrizione: BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index (Yee et al, 2010). BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items that are new or worse and are qualifying for the Grade B in any system (Isenberg et al, 2011). Determination of items that are new or worse qualifying for the Grade B will be according to the supplementary information for the numerical scoring of the BILAG- 2004 index (Yee et al, 2010)
  • Misura: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
  • Tempo: From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
  • Descrizione: Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
  • Misura: Percentage of participants with serious treatment-emergent adverse events during the study
  • Tempo: From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
  • Descrizione: A serious treatment-emergent adverse event (serious TEAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Is a congenital anomaly or birth defect Is an infection that requires treatment with parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above
  • Misura: Percentage of participants with treatment-emergent adverse events of special interest during the study
  • Tempo: From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
  • Descrizione: An adverse event of special interest is any AE that a regulatory authority has mandated be reported on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the administration of a UCB product/compound.
  • Misura: Percentage of participants with treatment-emergent adverse events of special monitoring during the study
  • Tempo: From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
  • Descrizione: An adverse event of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB.

CRITERI DI ELIGIBILITA'

  • Criteri di inclusione e esclusione

    Inclusion Criteria: - Rescreening will be allowed once during the study in case there is new evidence for an inclusion criterion that was not fulfilled at the first screening or in case a study participant no longer meets an exclusion criterion or screening period exceeded the maximum duration due to delays in screening processes - Study participant must be ≥16 years of age, unless restricted by local regulation, at the time of signing the Informed Consent form (ICF) - Study participants who have moderate to severe disease activity due to either persisting active SLE or due to an acute worsening of SLE in the scope of frequent flaring/relapsing-remitting systemic lupus erythematosus (SLE) despite stable standard of care (SOC) medication defined as: a. Diagnosed with SLE at least 24 weeks before the Screening Visit (Visit 1) study entry by a qualified physician b. Classified by 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE c. With serological evidence for SLE at Screening as demonstrated by at least 1 of the following: i) Evidence for anti-dsDNA (in central laboratory at Screening) ii) Either complement C3 < lower limit of normal (LLN) OR complement C4 2.5 mg/dL, or participant has proteinuria >3 g/day, or protein: creatinine ratio >340 mg/mmol at the Screening Visit


SESSO

Tutti


ETA' MINIMA

Età Minima: 16 Years
Età Massima: N/A


LUOGO

Sl0043 40084
Catania,

Sl0043 40472
Ferrara,

Sl0043 40514
Genova,

Sl0043 40291
Milano,

Sl0043 40448
Milano,

Sl0043 40471
Milano,

Sl0043 40509
Padova,

Sl0043 40148
Roma,

Sl0043 40492
Rozzano,

Sl0043 40473
Verona,

REFERENTE PER INFORMAZIONI

UCB Cares
001 844 599 2273
UCBCares@ucb.com