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 (IRB # 2022-0360)

Summary:

The purpose of this study (SL0044) is to evaluate the investigational drug Dapirolizumab Pegol in order to identify safety and efficacy of the drug for the treatment of active Systemic Lupus Erythematosus (SLE) in patients who are not responding to standard therapy. Dapirolizumab pegol is an antibody that targets CD40 ligand (CD40L), a protein in your immune system that affects T cell and B cell activity. Previous studies have shown that blocking CD40L is efficacious in treatment of inflammatory and autoimmune conditions. The results of early clinical studies have shown support for the use of Dapirolizumab Pegol for treatment of SLE.

Approximately 450 patients will be enrolled into this study worldwide, and approximately 2 patients will be from HSS. Study participants who meet the study's eligibility requirements and are enrolled will be randomized to receive either dapirolizumab pegol or placebo in a ratio of 2: 1. Treatment will be administered every month via intravenous infusion, with the last dose at Week 44. Study duration for a single subject will be 48 weeks plus a 2-week screening period and a 6-week safety follow-up period. The research staff will provide a schedule of assessments that illustrates when study subjects will be expected to attend study visits. Upon completion of the study, participants may be eligible for the open-label extension study, SL0046, to assess the long-term safety and tolerability of DZP treatment in study participants with SLE.

Inclusion Criteria:

Someone can participate in this study if they meet ALL of the following:

• At least 16 years of age and able to provide informed consent (if 16-17 years of age, then must be accompanied by a parent or guardian)
• Diagnosed with active SLE at least 24 weeks before screening
• Meets the EULAR/ACR 2019 classification criteria for SLE
• Have positive autoantibodies (ANA, or anti-dsDNA or anti-Smith) based on central laboratory screening
• Moderate to severe SLE disease activity as defined by the SLEDAI-2K and BILAG 2004 assessments
  • BILAG 2004 Grade B in ≥2 organ systems and/or Grade A in ≥1 organ systems AND
  • SLEDAI-2K ≥6 AND SLEDAI-2K without labs ≥4
• Taking standard of care SLE background therapies at stable dose for at least 8-12 weeks
  • Antimalarial treatment with corticosteroids and/or immunosuppressants
  • Treatment with corticosteroids and/or immunosuppressants if antimalarial treatment is not appropriate
  • ≤ 40 mg/day prednisone or other equivalent oral corticosteroid, stable ≥ 2 weeks prior to screening

Exclusion Criteria

Someone cannot participate in this study if they have ANY of the following: 

• History of anaphylaxis to latex, contrast agents, antibodies, or other human or murine proteins. Or, allergy/hypersensitivity to any components of Dapirolizumab Pegol including pegol or comparative drugs
• Another medical or psychiatric condition (including neuropsychiatric SLE and infections) that may confound SLE disease assessment and/or poses a danger to the participant
• Any cancer except the following treated cancers: cervical carcinoma, basal cell carcinoma, or dermatological squamous cell carcinoma
• Major surgery within 24 weeks prior to screening
• Significant blood loss or have donated/received  ≥ 450 mL of blood within 30 days of screening
  History ofthromboembolic events within 52 weeks of screening
• Study participant has a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE. Study participants with rheumatoid arthritis in their medical history are not considered as having an overlap syndrome and are therefore eligible
• Evidence of active or latent infections, including but not limited to:
  
  • Human Immunodeficiency Virus (HIV)
  • Hepatitis B or C
  • Herpes simplex virus or Herpes zoster
  • Tuberculosis (TB)
  • Other serious infections within the past 60 days requiring infusion therapy or prolonged hospitalization
• Excluded medication therapy:
  • Needing SOC treatment outside of that permitted by the study
  • Prohibited biologics/immunosuppressants within the following time frames, including but not limited to:
    • • Rituximab, Ofatumumab, Obinutuzimab, Ocrelizumab, Veltruzumab within 12 months
      • Cyclophosphamide, Vedolizumab, Ustekinumab, BIIB059 within 6 months
      • Belimumab, Tabalumab, Anifrolumab, Sifalimumab within 8-12 weeks
      • Abatacept, Eculizumab, ETI-201, Natalizumab, TACI-Ig, Tocilizumab, Rigerimod within 3 months
      • Tacrolimus, Pimecrolimus, Sirolimus, IV IG, Minocycline, JAK inhibitors, TYK 2 inhibitors within 4 weeks
• Other investigational drug within 3 months of screening or within 5 half-lives of the last dose
• Study participants who have received live/live attenuated vaccines within 6 weeks prior to the first study medication infusion or who plan to receive these vaccines during the study or up to 12 weeks after the final dose of study medication
• Pregnant, planning to become pregnant, or unwilling to use contraception through study and for 17 weeks after end of treatment in the study, or breastfeeding

Study Contact

Natasha Zarrin 
Clinical Research Coordinator 
zarrinn@hss.edu 
212.774.2967