Chronic Immune Thrombocytopenia MedDRA version: 14.1 Level: LLT Classification code 10051057 Term: Idiopathic thrombocytopenia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: BENLYSTA® (belimumab)
Product Name: belimumab
Product Code: GSK1550188
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belimumab
CAS Number: 356547-88-1
Current
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age & gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent 2. Disease severity: Diagnosis of chronic ITP for a minimum of 6 months with a platelet count of =75,000/µL at screening and a historical platelet count of =75,000/µL 2 to 6 months prior to screening. 3. ITP treatment: ITP patients stable either on no treatment or on a stable dose of corticosteroids (10mg/day prednisone or prednisone equivalent or less) and/or azathioprine (100mg/day or less) for a minimum of 30 days before screening. 4. ECG: Single QTc, 40 MlU/ml and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Secondary ITP: If the diagnosis of ITP is secondary to other conditions. 2. B-cell Prior Therapy: Have received treatment with any B cell targeted therapy at any time. 3. 364 Day Prior Therapy: Have received any of the following within 364 days prior to Day 0: • Abatacept. • A biologic investigational agent other than B cell targeted therapy. 4. 180 Day Prior Therapy: Have received any of the following within 180 days prior to Day 0: • Intravenous (IV) cyclophosphamide. • 3 or more courses of systemic corticosteroids for concomitant conditions (eg, asthma, atopic dermatitis. Topical or inhaled steroids are permitted). 5. 90 Day Prior Therapy: Have received any of the following within 90 days prior to Day 0: • High dose corticosteroid for treatment of ITP (> 100 mg/day prednisone or equivalent). • Splenectomy, plasmapheresis. 6. 60 Day Prior Therapy: Have received any of the following within 60 days, 5 halflives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to Day 0: • A non-biologic investigational agent. • Any other immunosuppressive/immunomodulatory agent with the exception of azathioprine and corticosteroids. • Eltrombopag, romiplostim. • Any steroid injection. Note: Inhaled steroids and Topical immunosuppressive agents are allowed. 7. 30 Day Prior to Screening Therapy: Have received any of the following within 30 days prior to Screening: • Intravenous immunoglobulin. • Corticosteroids greater than 10mg/day or azathioprine more than 100 mg/day. • Changes to corticosteroid or azathioprine therapy. 8. 30 Day Prior Therapy: Have received any of the following within 30 days prior to Day 0: • A live vaccine. 9. Haemorrhage: Disease status where, in the opinion of the investigator, the subject could be at risk of haemorrhage that threatens a vital organ. 10. Transplantation: Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant. 11. Cancer: Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin or carcinoma in situ of the uterine cervix. 12. Acute or chronic infection: Have required management of acute or chronic infections, as follows: • Currently on any suppressive therapy for a chronic infection • Hospitalisation for treatment of infection within 60 days prior to Day 0. • Use of parenteral antibiotics within 60 days prior to Day 0. 13. Other diseases/conditions: Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to ITP which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk. or Have a planned surgical procedure or a history of any other medical disease, laboratory abnormality, or condition that, in the opinion of the investigator, makes the subject unsuitable for the study. 14. Hepatitis: A positive screening Hepatitis C antibody result or serologic evidence of Hepatitis B (HB) infection based on the results of testing for HBsAg, anti-HBc and anti-HBs as follows: • Patients positive for HBsAg are excluded. • Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody and with no history of Hepatitis B vaccination are excluded. • Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies are excluded. • Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody are e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate the safety and tolerability of belimumab 10mg/kg in ITP - To assess the pharmacokinetics of belimumab 10mg/kg in ITP - To evaluate whether belimumab can modulate antigen specific lymphocyte responses, general serum autoantibody levels, serum cytokine/chemokine levels and transcriptomic profiling - To evaluate whether any demonstrated modulation of B cells and the immune system can, through selected pharmacodynamic (PD) assays, be directly linked to clinical efficacy such that the PD assays could be used as biomarkers ;Main Objective: - To evaluate whether belimumab can demonstrate clinical efficacy in ITP - To evaluate whether belimumab can modulate anti-platelet autoantibodies in patients with detectable baseline levels of these antibodies;Primary end point(s): - Change from baseline in platelet count - Change from baseline in serum and platelet-bound GPIIb/IIIa and/or GPIb/IX autoantibodies (in patients with detectable baseline levels of these antibodies);Timepoint(s) of evaluation of this end point: Week 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy - Time to first response (platelet count increase >20,000/µL from baseline) - Incidence of response of platelet count increase >20,000/µL from baseline (Day 0) at week 28 - Incidence of complete response as defined by platelet count to >100,000 at week 28 - Incidence of subjects with = 2 times baseline platelet count at week 28 Safety and tolerability - Adverse Events (AEs) - Change from baseline and number of subjects outside the normal range for blood pressure, heart rate, temperature - Change from baseline in clinical chemistry and haematology parameters - Immunogenicity Pharmacokinetics - Individual serum concentrations of belimumab and data permitting summary PK parameters Pharmacodynamics/biomarkers - Change in serum and/or platelet bound anti-platelet antibodies by visit - Change in relevant B cell and T cell sub-populations and BLyS receptor expression (by FACS analysis) by visit - Change in antigen-specific B cells and T cells by visit - Serum cytokine/chemokine and autoantibody profile by visit - Change in transcriptomic profile by visit ;Timepoint(s) of evaluation of this end point: Weeks 0, 2, 4, 8, 12, 16, 20, 24, 28, 40, 52 (dependent on endpoint) | — |
Countries
Germany, United Kingdom
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed