A study to learn if dapirolizumab pegol works and is safe in people with moderately to severely active systemic lupus erythematosus (SLE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biopharma

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

28 Nov 2024 → ongoing

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

UCB Biopharma SRL

External identifiers

EU CT number

2023-508191-11-00

EudraCT number

2019-003407-35

WHO UTN

U1111-1298-3467

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacodynamic, Pharmacogenetic, Pharmacokinetic

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

Secondary objectives 1

1. Evaluate the ability of dapirolizumab pegol (DZP) as an add-on treatment to standard of care (SOC) medication: - to achieve remission of at least 1 moderate or 2 mild SLE symptoms - to achieve long-term control of disease activity - to achieve and maintain the treat-to-target goal: low disease activity with low/acceptable glucocorticoid dose over time - to improve the participant health experience related to overall fatigue - to reduce glucocorticoid dose to low doses - to achieve components of the composite primary endpoint - to achieve endpoints supporting secondary endpoint on BILAG flare prevention -to achieve improvement of disease activity as measured by numerical disease state score commonly used in clinical practice -to assess patient reported outcomes To evaluate the safety and tolerability of DZP as add-on treatment to SOC medication

Conditions and MedDRA coding

Systemic lupus erythematosus (SLE)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Study participant must be ≥16 years of age, (≥18 years of age for China), 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 glucocorticoids and/or immunosuppressants or as stand-alone treatment if justified OR ◦ Treatment with glucocorticoids 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 1

1. - 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 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 within the time frame (Wash- Out Period) listed 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achievement of British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) response at Week 48

Secondary endpoints 14

1. Achievement of SRI 4 response at Week 48
2. Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 48
3. Achievement of LLDAS at Week 40 and maintaining LLDAS at Weeks 44 and 48
4. Change from Baseline to Week 48 in the FATIGUE-PRO Total score
5. Percentage of participants having a reduction in glucocorticoid dose from >7.5mg/day prednisone-equivalent dose at Baseline to ≤7.5mg/day at Week 36 and maintained through Week 48
6. Achievement of BILAG 2004 improvement without worsening at Week 48
7. Change from Baseline in PGA at Week 48
8. Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48
9. Change from Baseline in SLEDAI-2K at Week 48
10. Change from Baseline in FACIT-Fatigue score at Week 48
11. Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
12. Percentage of participants with serious treatment-emergent adverse events during the study
13. Percentage of participants with treatment-emergent adverse events of special interest during the study
14. Percentage of participants with treatment-emergent adverse events of special monitoring during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biopharma

Sponsor organisation

UCB Biopharma

Address

Researchdreef 60

City

Anderlecht

Postcode

1070

Country

Belgium

Scientific contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Public contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Third parties 23

Locations

9 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 342 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

22 submissions — initial application plus substantial / non-substantial modifications