Dapirolizumab Pegol for Lupus

(PHOENYCS FLY Trial)

Recruiting at 217 trial locations

Overseen By UCB Cares

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB Biopharma SRL

Must be taking: Antimalarials, Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Malignancy, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called dapirolizumab pegol (a pegylated anti-CD40L antibody) to determine its effectiveness for people with lupus, a condition where the immune system attacks the body, causing inflammation and pain. The goal is to see if adding this treatment to usual medications can improve long-term symptoms for those with moderate to severe lupus. Participants will receive either the new treatment or a placebo (a harmless, inactive substance) to compare effects. Suitable candidates for this trial are those diagnosed with lupus for at least six months who still experience frequent flare-ups despite regular medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop your current medications. In fact, it mentions that participants should be on stable standard of care medications, which may include antimalarials, corticosteroids, or immunosuppressants.

Is there any evidence suggesting that dapirolizumab pegol is likely to be safe for humans?

A previous study tested dapirolizumab pegol on both healthy individuals and those with systemic lupus erythematosus (SLE). The results showed it was well-tolerated, with no safety concerns. This treatment blocks a specific signal that calms the overactive immune system, a common issue in lupus. Although some trials did not always meet their main goals, the safety results have been reassuring. So far, the treatment appears safe, with no significant side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Dapirolizumab pegol is unique because it targets CD40 ligand, a molecule involved in the immune response, which is a different approach compared to standard lupus treatments like hydroxychloroquine and corticosteroids. By focusing on this specific target, dapirolizumab pegol aims to modulate the immune system more precisely, potentially reducing inflammation and tissue damage associated with lupus. Researchers are excited about this treatment because it offers a novel mechanism of action that could provide relief for patients who do not respond adequately to existing therapies.

What evidence suggests that dapirolizumab pegol could be an effective treatment for lupus?

Research has shown that dapirolizumab pegol (DZP), which participants in this trial may receive, may help treat lupus. In a previous study, patients who took DZP experienced less disease activity after 24 weeks compared to those who took a placebo. DZP blocks a protein called CD40L, which reduces harmful immune responses involved in lupus. The treatment was well tolerated, with no major safety concerns reported. These findings suggest DZP could effectively manage lupus symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Are You a Good Fit for This Trial?

This trial is for individuals over the age of 16 with moderately to severely active systemic lupus erythematosus. Participants must have certain autoantibodies (anti-Sm, Anti-SSA/Ro, anti-SSB/La or anti-dsDNA) and meet specific disease activity criteria. They should be on standard treatments like antimalarials, corticosteroids, or immunosuppressants.

Inclusion Criteria

I am 16 years or older.

I have anti-Smith antibodies.

I have had positive tests for anti-dsDNA antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapirolizumab pegol or placebo as an add-on treatment to standard of care medication to achieve clinically relevant long-term improvement of moderate to severe disease activity

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapirolizumab Pegol

Trial Overview The study tests if adding dapirolizumab pegol (DZP) to standard care helps people with severe lupus symptoms improve long-term. Some participants will receive DZP while others get a placebo; both groups continue their usual medications.

How Is the Trial Designed?

Group I: Dapirolizumab pegol Experimental Treatment 1 Intervention

Study participants will receive dapriolizumab pegol throughout the Treatment Period.

Group II: Placebo Placebo Group 1 Intervention

Study participants will receive placebo throughout the Treatment Period.

Who Is Running the Clinical Trial?

UCB Biopharma SRL

Lead Sponsor

Trials

118

Recruited

23,200+

Jean-Christophe Tellier

UCB Biopharma SRL

Chief Executive Officer since 2015

MD from University of Reims Champagne-Ardenne, Rheumatology specialization from University of Paris V, Executive business programs at Harvard and INSEAD

Dr. Iris Loew-Friedrich

UCB Biopharma SRL

Chief Medical Officer since 2014

MD from University of Leuven, PhD in Medical Sciences from University of Leuven

Published Research Related to This Trial

In a 32-week study involving 24 patients with systemic lupus erythematosus (SLE), dapirolizumab pegol was found to be safe, with no serious adverse events reported and only mild to moderate side effects that resolved without intervention.

The treatment showed promising efficacy, with 46% of patients on dapirolizumab pegol achieving a significant clinical response compared to only 14% in the placebo group, indicating its potential as a biological treatment for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles. Chamberlain, C., Colman, PJ., Ranger, AM., et al.[2018]

CDP7657, a PEGylated anti-CD40L antibody fragment, was well tolerated in a phase I study involving 28 healthy individuals and 17 patients with systemic lupus erythematosus (SLE), with most adverse events being mild or moderate.

The pharmacokinetics of CDP7657 were predictable and dose-proportional, and there were no significant safety concerns, supporting its potential for further investigation as a treatment for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus. Tocoian, A., Buchan, P., Kirby, H., et al.[2018]

Dapirolizumab pegol, currently in phase 3 trials for systemic lupus erythematosus (SLE), shows dose-proportional pharmacokinetics and effectively increases the likelihood of patients transitioning from 'Nonresponder' to 'Responder' based on the British Isles Lupus Assessment Group criteria.

The study found that maintaining higher concentrations of dapirolizumab pegol is crucial for sustaining treatment response, as the effective concentration needed to prevent relapse ('Responder' to 'Nonresponder') is significantly higher than that required to achieve an initial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response for Dapirolizumab Pegol From a Phase 2b Trial in Patients With Systemic Lupus Erythematosus. Acharya, C., Magnusson, MO., Vajjah, P., et al.[2023]

Dapirolizumab pegol (DZP) showed improvements in clinical and immunological outcomes for patients with moderately to severely active systemic lupus erythematosus (SLE) after 24 weeks, although the primary dose-response relationship was not statistically significant.

DZP was well tolerated with low incidences of serious adverse events, suggesting it is a safe option for SLE treatment, warranting further investigation into its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. Furie, RA., Bruce, IN., Dörner, T., et al.[2022]

CDP7657, a high affinity PEGylated anti-CD40L antibody fragment, effectively inhibited immune responses in Cynomolgus monkeys without causing thrombotic events, unlike the previously tested hu5c8 antibody.

The study demonstrated that anti-CD40L antibodies lacking a functional Fc region, such as CDP7657, do not activate platelets and retain their therapeutic efficacy, suggesting a safer alternative for treating systemic lupus erythematosus and other autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. Shock, A., Burkly, L., Wakefield, I., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9194804/

Phase 2, randomized, placebo-controlled trial of ... DZP appeared to be well tolerated, and patients exhibited improvements across multiple clinical and immunological measures of disease activity after 24 weeks ...

2. investors.biogen.com investors.biogen.com/news-releases/news-release-details/biogen-present-additional-results-phase-3-study-dapirolizumab

Biogen to Present Additional Results from Phase 3 Study of ... Dapirolizumab pegol inhibits CD40L signaling which has been shown to reduce B cell activation and autoantibody production, mitigate type 1 ...

3. ard.bmj.com ard.bmj.com/content/early/2017/08/04/annrheumdis-2017-211388?versioned=true

Repeated administration of dapirolizumab pegol in a ... Dapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1568997220302433

Rediscovering the role of the CD40–CD40L pathway in ... The CD40–CD40L pathway is central to SLE pathogenesis and the generation of autoantibodies and their deposition in the kidneys, resulting in renal injury in ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25784719/

First-in-human trial of the safety, pharmacokinetics and ... Single doses of CDP7657 showed predictable PK in healthy individuals and patients with SLE and were well tolerated, with no safety signals of concern.

6. guidetopharmacology.org guidetopharmacology.org/GRAC/LigandDisplayForward?tab=refs&ligandId=11123

dapirolizumab pegol | Ligand page First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and ...

7. db.antibodysociety.org db.antibodysociety.org/db0/497/

Dapirolizumab pegol Clinical Immunoconjugate, Pegylated Oct 2018: Dapirolizumab pegol (DZP) did not meet the primary endpoint of demonstrating a dose response at 24 weeks on the British Isles Lupus Assessment Group ( ...