Dapirolizumab Pegol for Lupus

(PHOENYCS FLY Trial)

Recruiting at117 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: UCB Biopharma SRL

Must be taking: Antimalarials, Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Malignancy, Heart disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Dapirolizumab Pegol for treating lupus?

Research shows that Dapirolizumab Pegol, which blocks a protein called CD40L involved in immune responses, has been well tolerated and led to improvements in lupus disease activity in clinical trials. It increased the likelihood of patients responding positively to treatment, suggesting it could be an effective option for managing lupus. ^{1 2 3 4 5}

Is Dapirolizumab Pegol safe for humans?

Dapirolizumab Pegol has been tested in both healthy individuals and patients with systemic lupus erythematosus (SLE) and was generally well tolerated without significant safety concerns. Unlike some other treatments targeting the same pathway, it did not show an increased risk of blood clots in studies. ^{1 2 3 4 5}

How is the drug dapirolizumab pegol different from other lupus treatments?

Dapirolizumab pegol is unique because it targets the CD40 ligand, a protein involved in immune cell activation, which may help reduce inflammation in lupus without the increased risk of blood clots seen in similar treatments. It is a PEGylated antibody fragment, which means it is modified to stay in the body longer, potentially improving its effectiveness. ^{1 2 3 4 5}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dapirolizumab Pegol (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. England 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response for Dapirolizumab Pegol From a Phase 2b Trial in Patients With Systemic Lupus Erythematosus. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. [2022]

4. England 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. [2018]

5. England 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. [2018]