The BeLimumab Antiphospholipid Syndrome Trial (BLAST) (BLAST)

Open-label, Prospective, Phase II Descriptive Pilot Trial of Belimumab Therapy for Refractory and/or Non-criteria Manifestations of Antiphospholipid Syndrome

AIM: The primary objective of the BeLimumab Antiphospholipid Syndrome Trial (BLAST) is to evaluate the safety and tolerability of belimumab for up to 24 months in patients with persistent aPL positivity and clinical features attributable to aPL that are resistant to warfarin and/or heparin.

Study Overview

• Status: Recruiting
• Conditions: Antiphospholipid Syndrome
• Intervention / Treatment: Drug: Belimumab

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Italy
  • Piedmont
    • Turin, Piedmont, Italy, 10154
      • Recruiting
      • San Giovanni Bosco Hospital
      • Contact: Savino Sciascia, MD;PhD; Phone Number: +390112402051; Email: savino.sciascia@unito.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Positive aPL profile defined as: Positive lupus anticoagulant test as defined by the International Society on Thrombosis and Haemostasis, on two or more occasions, at least 12 weeks apart and/or Positive anticardiolipin antibody (aCL) immunoglobulin G(Ig)G/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart and/or Positive anti-β2-glycoprotein-I (aβ2GPI) IgG/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart

AND

• Clinical features attributable to aPL that are resistant to warfarin and/or heparin:

• Recurrent thrombosis despite ongoing anticoagulation and/or
• Persistent thrombocytopenia and/or
• Persistent autoimmune hemolytic anemia and/or
• Cardiac valve disease and/or
• Chronic skin ulcers and/or
• Renal thrombotic microangiopathy and/or
• Cognitive dysfunction with/without white matter changes

Exclusion Criteria:

• >=4/11 American College of Rheumatology Classification Criteria for SLE
• Acute thrombosis (arterial or venous acute thrombosis diagnosis less than 30 days before study screening)
• History of stroke Acute or chronic pancreatitis
• Pregnancy
• Have a history of malignant neoplasm within the last 5 years except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years
• Have evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, poses a significant suicide risk
• Have a history of a primary immunodeficiency
• Have a significant IgG deficiency (IgG level < 400 mg/dL)
• Have an IgA deficiency (IgA level < 10 mg/dL)
• Known active bacterial, viral fungal mycobacterial, or other infection
• Infection history:
• Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)
• Hospitalization for treatment of infection within 60 days of Day 0.
• Use of parenteral (IV or IM) antibiotics (anti-bacterial, antiviral, anti-fungal, or antiparasitic agents) within 60 days of Day 0
• Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0
• Have a historically positive HIV test or test positive at screening for HIV
• Hepatitis status:
• Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows:
• Patients positive for HBsAg or HBcAb are excluded
• Positive test for Hepatitis C antibody
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
• Have any other clinically significant abnormal laboratory value in the opinion of the investigator
• If Women of Child-Bearing Potential (WCBP) are included, please see special instructions below.
• Have any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; INTERVENTION DRUG: BELIMUMAB 10 MG/KG	Drug: Belimumab; INTERVENTION DRUG: BELIMUMAB 10 MG/KG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Adverse Events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Efficacy of Belimumab-thrombocytopenia	Outcome measures scored as complete response (CR), partial (PR), and none (NR) at 24, 52, 104 weeks. For thrombocytopenia, CR defined as a platelet count of ≥150×109/μl,PR as 100-149,and NR as <100.	104 weeks
The Efficacy of Belimumab-CVD	Outcome measures scored as complete response (CR), partial (PR), and none (NR) at 24, 52, 104 weeks.For CVD,CR defined as the disappearance of cardiac lesions, PR as 50%improvement,and NR as no change.	104 weeks
The Efficacy of Belimumab-renal involvement	Outcome measures scored as complete response (CR), partial (PR), and none (NR) at 24, 52, 104 weeks. For aPL nephropathy, CR defined as a normal serum creatinine level, inactive urinary sediment, and urinary protein: creatinine 0.5;PR as a serum cr level 15% above baseline, RBCs per high-power field 50% above baseline with no casts, 50%improvement in the urinary prt:cr, and estimated GFR 10%above baseline; and NR as the absence of C/PR.	104 weeks
The Efficacy of Belimumab-cognitive impairment	Outcome measures scored as complete response (CR), partial (PR), and none (NR) at 24, 52, 104 weeks. For cognitive dysfunction,CR defined as normalization of the cognitive impairment index with 50%improvement,PR as abnormal index with 50%, and NR as no change.	104 weeks
The Efficacy of Belimumab-thrombosis	Rate of documented thrombotic events	104 weeks
Change in aPL profile	Change in aPL levels at 24, 52, 104 weeks	104 weeks

Collaborators and Investigators

• Sponsor: University of Turin, Italy

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease; Syndrome; Antiphospholipid Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: APSGB01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No