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

UCB

Status and phase: Enrolling; Phase 3

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: DZP; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06617325

2023-508191-11 (Registry Identifier)

U1111-1298-3467 (Other Identifier)

SL0044

2019-003407-35 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 450 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• 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 systemic lupus erythematosus (SLE) or due to an acute worsening of SLE in the scope of frequent relapsing-remitting SLE despite stable standard of care(SOC) medication defined as:

  a. Diagnosed with SLE at least 24 weeks before the Screening Visit 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 (defined as evidence for anti-dsDNA antibodies in central laboratory) ii) Either complement C3 <lower limit of normal (LLN) OR complement C4 <LLN 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 or source verifiable history)

  2. Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory)

  3. Historical evidence for anti-dsDNA antibodies

  4. Anti-ribonucleoprotein (RNP) autoantibodies (central laboratory) 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 the Screening Visit AND
     • SLEDAI-2K without labs ≥4 at Baseline Visit e. Receiving the following standard of care (SOC) medications 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 antimalarial treatment is not appropriate (ie, there is documented intolerance in medical history, documented lack of efficacy, contraindications, or lack of availability)

     Exclusion Criteria:

• Study participant has any medical or psychiatric condition (including conditions due to neuropsychiatric 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. This includes systemic reactions due to latex allergy

• Study participant has a history of malignancy, except the following treated cancers: cervical carcinoma in situ (after complete resection [eg, curettage, electrodesiccation] not later than 4 weeks prior to the Screening Visit [V1]), 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 a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE

• Study participant has evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection at any time prior to or during the study

• Study participant has clinically significant active or latent infection

• Study participant had a reactivated latent infection (eg, 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 used the prohibited medications defined in the Protocol

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

• Study participant has participated in another study of an investigational medicinal product (IMP) within the previous 12 weeks or 5 half-lives of the 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 (eGFR) <30 mL/min/1.73m2, or serum creatinine >2.5 mg/dL, or participant has proteinuria >3g/day, or protein:creatinine ratio >340 mg/mmol at the Screening Visit

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups, including a placebo group

Dapirolizumab pegol

Experimental group

Description:

Study participants will receive dapriolizumab pegol throughout the Treatment Period.

Treatment:

Drug: DZP

Placebo

Placebo Comparator group

Description:

Study participants will receive placebo throughout the Treatment Period.

Treatment:

Other: Placebo