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

Systemic Lupus Erythematosus Clinical Trial

— PHOENYCS GO  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04294667
• Other study ID #: SL0043
• Secondary ID: 2019-003406-27
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 12, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: June 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 321
• Est. completion date: September 30, 2024
• Est. primary completion date: May 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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 <LLN OR elevated erythrocyte-bound complement C4d (where available) as measured by central laboratory iii) Antinuclear antibodies with a titer of at least 1:80 confirmed by central laboratory in combination with evidence of at least 1 of the following SLE typical autoantibodies:

1. Anti-Smith (anti-Sm) antibodies (central laboratory) 2. Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory) 3. Historic evidence for anti-dsDNA antibodies

d. Moderately to severely active defined as

• British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) Grade B in =2 organ systems and/or a BILAG 2004 Grade A in =1 organ systems at Screening and Baseline Visit AND

• Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) =6 at Screening Visit AND

• SLEDAI-2K without labs =4 at Baseline Visit

e. Receiving the following SOC medication at stable dose:

• Antimalarial treatment in combination with corticosteroids and/or immunosuppressants or as stand-alone treatment if justified OR Treatment with corticosteroids and/or immunosuppressants if anti-malarial treatment is not possible

Exclusion Criteria:

• Study participant has any medical or psychiatric condition (including conditions due to neuropsychiatric systemic lupus erythematosus (SLE)) that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study. This includes study participants with a life threatening condition

• Study participant has a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies

• Study participant has a history of malignancy, except the following treated cancers:

cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma

• Study participant has an increased risk for thromboembolic events due to an ongoing heart disease or due to a medical device, including but not limited to vascular graft, valvular heart disease, atrial fibrillation, or a heart rhythm disorder

• Study participant has evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection

• Study participant had a reactivated latent infection (example, cytomegalovirus, herpes simplex virus, or herpes zoster infection) or opportunistic infection (including but not limited to, pneumocystis, cytomegalovirus, or severe herpes zoster infection) within 12 weeks prior to the first study medication infusion (Visit 2), or is currently receiving suppressive therapy for an opportunistic infection

• Study participants who have received live/live attenuated vaccines within 6 weeks prior to the first study medication infusion

• Study participant has clinically significant active or latent infection

• Study participant has a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE

• Study participant takes any protocol defined prohibited concomitant medication

• Study participant has previously been randomized within this study or participant has previously been assigned to treatment with dapirolizumab pegol (DZP) in a study evaluating DZP

• Study participant has participated in another study of an IMP within the previous 12 weeks or 5 half-lives of the investigational medicinal product (IMP) whatever is longer or is currently participating in another study of an IMP

• Study participant has chronic kidney failure stage 4, manifested by estimated glomerular filtration rate <30mL/min/1.73m^2, or serum creatinine >2.5 mg/dL, or participant has proteinuria >3 g/day, or protein: creatinine ratio >340 mg/mmol at the Screening Visit

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• DZP
Subjects will receive dapirolizumab pegol at prespecified time-points.

Other:
• Placebo
Subjects will receive placebo at prespecified time-points.

Locations

Country	Name	City	State
Argentina	Sl0043 60002	Capital Federal
Argentina	Sl0043 60001	Ciudad Autonoma de Buenos Aire
Argentina	Sl0043 60029	Mendoza
Argentina	Sl0043 60003	Quilmes
Argentina	Sl0043 60022	Quilmes
Argentina	Sl0043 60011	San Juan
Argentina	Sl0043 60014	Tucuman
Australia	Sl0043 30020	Parkville
Australia	Sl0043 30025	St Albans
Austria	Sl0043 40388	Graz
Austria	Sl0043 40387	Wien
Belgium	Sl0043 40123	Bruxelles
Belgium	Sl0043 40060	Liege
Bulgaria	Sl0043 40006	Plovdiv
Bulgaria	Sl0043 40189	Plovdiv
Bulgaria	Sl0043 40522	Plovdiv
Bulgaria	Sl0043 40380	Sofia
Canada	Sl0043 50374	Calgary
Canada	Sl0043 50337	Edmonton
Canada	Sl0043 50259	Rimouski
Canada	Sl0043 50045	Toronto
Canada	Sl0043 50044	Trois-rivieres
Chile	Sl0043 60021	Providencia, Santiago
Chile	Sl0043 60018	Santiago
Chile	Sl0043 60030	Santiago
Chile	Sl0043 60015	Santiago de Chile
Colombia	Sl0043 60013	Barranquilla
Colombia	Sl0043 60019	Barranquilla
Colombia	Sl0043 60006	Bogota
Colombia	Sl0043 60027	Bogota
Colombia	Sl0043 60016	Bucaramanga
Colombia	Sl0043 60007	Chia
Colombia	Sl0043 60028	Medellín
Colombia	Sl0043 60031	Monteria
Czechia	Sl0043 40066	Praha 2
Denmark	Sl0043 40489	Odense
France	Sl0043 40506	Montpellier Cedex 5
France	Sl0043 40505	Paris Cedex 12
Germany	Sl0043 40386	Cologne
Germany	Sl0043 40322	Dessau
Germany	Sl0043 40356	Dresden
Germany	Sl0043 40072	Freiburg
Germany	Sl0043 40024	Hanover
Germany	Sl0043 40027	Herne
Germany	Sl0043 40078	Leipzig
Germany	Sl0043 40402	Tübingen
Greece	Sl0043 40378	Athens
Greece	Sl0043 40377	Crete
Greece	Sl0043 40501	Haidari - Athens
Greece	Sl0043 40507	Larisa
Greece	Sl0043 40375	Thessaloniki
Hungary	Sl0043 40412	Budapest
Hungary	Sl0043 40411	Debrecen
Hungary	Sl0043 40413	Gyula
Hungary	Sl0043 40031	Szeged
Hungary	Sl0043 40499	Szekesfehervar
Italy	Sl0043 40084	Catania
Italy	Sl0043 40472	Ferrara
Italy	Sl0043 40514	Genova
Italy	Sl0043 40291	Milano
Italy	Sl0043 40448	Milano
Italy	Sl0043 40471	Milano
Italy	Sl0043 40509	Padova
Italy	Sl0043 40148	Roma
Italy	Sl0043 40492	Rozzano
Korea, Republic of	Sl0043 20141	Busan
Korea, Republic of	Sl0043 20106	Daejeon
Korea, Republic of	Sl0043 20108	Incheon
Korea, Republic of	Sl0043 20104	Seoul
Mexico	Sl0043 50317	Chihuahua
Mexico	Sl0043 50250	Cuernavaca
Mexico	Sl0043 50249	Guadalajara
Mexico	Sl0043 50271	Leon
Mexico	Sl0043 50252	Merida
Mexico	Sl0043 50251	Monterrey
Peru	Sl0043 60026	Arequipa
Peru	Sl0043 60008	Lima
Peru	Sl0043 60009	Lima
Peru	Sl0043 60023	Lima
Philippines	Sl0043 20110	Angeles
Philippines	Sl0043 20182	Davao
Philippines	Sl0043 20181	Makati
Philippines	Sl0043 20111	Manila
Poland	Sl0043 40482	Bialystok
Poland	Sl0043 40119	Bydgoszcz
Poland	Sl0043 40398	Katowice
Poland	Sl0043 40490	Krakow
Poland	Sl0043 40502	Krakow
Poland	Sl0043 40037	Lublin
Poland	Sl0043 40151	Lublin
Poland	Sl0043 40483	Nadarzyn
Poland	Sl0043 40044	Poznan
Poland	Sl0043 40090	Poznan
Poland	Sl0043 40097	Warszawa
Poland	Sl0043 40098	Warszawa
Poland	Sl0043 40394	Warszawa
Poland	Sl0043 40397	Wroclaw
Poland	Sl0043 40481	Wroclaw
Romania	Sl0043 40464	Bucharest
Romania	Sl0043 40383	Bucuresti
Romania	Sl0043 40382	Galati
Serbia	Sl0043 40393	Belgrade
Serbia	Sl0043 40461	Belgrade
Serbia	Sl0043 40466	Kragujevac
Serbia	Sl0043 40392	Novi Sad
Spain	Sl0043 40045	A Coruna
Spain	Sl0043 40160	Barcelona
Spain	Sl0043 40341	Málaga
Spain	Sl0043 40521	Mérida
Spain	Sl0043 40101	Sabadell
Spain	Sl0043 40400	Sevilla
Spain	Sl0043 40099	Vigo
Taiwan	Sl0043 20113	Taichung City
Taiwan	Sl0043 20142	Taichung City
Taiwan	Sl0043 20095	Taipei
Taiwan	Sl0043 20099	Taipei City
Taiwan	Sl0043 20082	Taoyuan City
United States	Sl0043 50263	Amarillo	Texas
United States	Sl0043 50368	Atlanta	Georgia
United States	Sl0043 50382	Atlanta	Georgia
United States	Sl0043 50050	Beckley	West Virginia
United States	Sl0043 50338	Bellaire	Texas
United States	Sl0043 50383	Beverly Hills	California
United States	Sl0043 50140	Birmingham	Alabama
United States	Sl0043 50239	Brandon	Florida
United States	Sl0043 50010	Brooklyn	New York
United States	Sl0043 50366	Canton	New York
United States	Sl0043 50238	Charlotte	North Carolina
United States	Sl0043 50310	Chicago	Illinois
United States	Sl0043 50330	Cincinnati	Ohio
United States	Sl0043 50418	Colleyville	Texas
United States	Sl0043 50288	Cumberland	Maryland
United States	Sl0043 50057	Dallas	Texas
United States	Sl0043 50304	Dallas	Texas
United States	Sl0043 50339	Denver	Colorado
United States	Sl0043 50219	Detroit	Michigan
United States	Sl0043 50020	Duncansville	Pennsylvania
United States	Sl0043 50362	Gainesville	Florida
United States	Sl0043 50333	Grand Blanc	Michigan
United States	Sl0043 50266	Great Neck	New York
United States	Sl0043 50015	Hagerstown	Maryland
United States	Sl0043 50147	Hershey	Pennsylvania
United States	Sl0043 50474	Hopkinsville	Kentucky
United States	Sl0043 50240	Idaho Falls	Idaho
United States	Sl0043 50001	Jackson	Tennessee
United States	Sl0043 50257	La Jolla	California
United States	Sl0043 50275	La Palma	California
United States	Sl0043 50285	Lake Charles	Louisiana
United States	Sl0043 50273	Las Vegas	Nevada
United States	Sl0043 50378	Loma Linda	California
United States	Sl0043 50258	Los Angeles	California
United States	Sl0043 50264	Manhasset	New York
United States	Sl0043 50036	Mesquite	Texas
United States	Sl0043 50122	Miami	Florida
United States	Sl0043 50321	Morgantown	West Virginia
United States	Sl0043 50367	New Haven	Connecticut
United States	Sl0043 50077	New York	New York
United States	Sl0043 50334	New York	New York
United States	Sl0043 50262	Oklahoma City	Oklahoma
United States	Sl0043 50340	Orange	California
United States	Sl0043 50059	Ormond Beach	Florida
United States	Sl0043 50364	Philadelphia	Pennsylvania
United States	Sl0043 50052	Phoenix	Arizona
United States	Sl0043 50365	Pittsburgh	Pennsylvania
United States	Sl0043 50324	Plantation	Florida
United States	Sl0043 50331	Poway	California
United States	Sl0043 50377	San Diego	California
United States	Sl0043 50316	San Leandro	California
United States	Sl0043 50267	Seattle	Washington
United States	Sl0043 50360	Skokie	Illinois
United States	Sl0043 50061	Spokane	Washington
United States	Sl0043 50241	Syracuse	New York
United States	Sl0043 50283	Tampa	Florida
United States	Sl0043 50329	Tampa	Florida
United States	Sl0043 50328	Tucson	Arizona
United States	Sl0043 50341	Washington	District of Columbia
United States	Sl0043 50179	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Serbia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of BICLA response at Week 48	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.	Week 48
Secondary	Achievement of BICLA response at Week 24	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.	Week 24
Secondary	Achievement of BICLA response at Week 12	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.	Week 12
Secondary	Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 48	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).	During Treatment Period up to Week 48
Secondary	Achievement of LLDAS in =50% of post-Baseline visits through Week 48	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	During Treatment Period up to Week 48
Secondary	Change from Baseline in SLEDAI-2K at Week 48	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.	From Baseline (Day 1) to Week 48
Secondary	Achievement of BILAG improvement without worsening at Week 48	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.	Week 48
Secondary	Change from Baseline in PGA at Week 48	Physician's Global Assessment of Disease (PGA) The Investigator will rate the overall status of the study participant.	From Baseline (Day 1) to Week 48
Secondary	Achievement of SRI4 response at Week 48	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	Week 48
Secondary	Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48	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)	During Treatment Period up to Week 48
Secondary	Time to severe BILAG Flare through Week 48	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).	During Treatment Period up to Week 48
Secondary	Time to moderate/severe BILAG flare through Week 48	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)	During Treatment Period up to Week 48
Secondary	Percentage of participants with treatment-emergent adverse events (TEAEs) during the study	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.	From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
Secondary	Percentage of participants with serious treatment-emergent adverse events during the study	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	From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
Secondary	Percentage of participants with treatment-emergent adverse events of special interest during the study	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.	From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
Secondary	Percentage of participants with treatment-emergent adverse events of special monitoring during the study	An adverse event of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB.	From Baseline (Day 1) until Safety Follow-Up (up to Week 54)