Health Condition 1: null- Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects
Conditions
Interventions
Intervention1: Sym001 drug product: The Sym001 drug product contains 0.6 mg/mL of Sym001 recombinant human anti-RhD IgG in 50 mM citrate-phosphate buffer, 150 mM sodium chloride and 0.05% polysorbate
Sponsors
Symphogen AS
Eligibility
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any trial-related procedures. 2. Age > 18. 3. Confirmed presence of thrombocytopenia with platelet count 200 μg/kg a maximum of 1 subject with platelet counts 1 hour interval between each other and both being 4. History of isolated ITP (thrombocytopenia with no known aetiology, blood smear showing normal appearing platelets or if performed, a bone marrow showing adequate thrombopoïesis and normal erythroid and myeloid morphology). 5. RhD- positive serology. 6. Previous treatment and response to first line therapy for ITP (corticosteroids, anti-D or IVIg), with response being defined as an increase in platelet count to >=30,000/mm3. 7. If female and of child-bearing potential, subject has a negative pregnancy test at screening. 8. If subject is a female of child-bearing potential, subject agrees to use a medically accepted form of contraception from the time of enrolment (at screening) to completion of all follow-up trial visits.
Exclusion criteria
Exclusion criteria: 1. Known clinical picture suggestive of other causes of thrombocytopenia, especially systemic lupus erythematosus, antiphospholipid syndrome, Evans syndrome, immunodeficiency states, lymphoproliferative disorders, liver disease, ingestion of drugs such as quinidine/quinine, heparin and sulfonamides and hereditary thrombocytopenia confirmed by relevant laboratory findings. 2. Suspected infection with HIV, hepatitis C, H. pylori unless corresponding laboratory tests are negative 3. Clinical splenomegaly (the spleen should not be palpable at more than 1 finger breadth below the costal margin). 4. History of abnormal bone marrow examination (except ITP-typical megacaryocytosis). 5. At pre-dose visit: an ongoing haemorrhage corresponding to a grade 3 or 4 on the WHO bleeding scale. 6. History of anaphylaxis or hypersensitivity reactions following anti-D treatment. 7. Current immune haemolytic anaemia. 8. Underlying haemolytic condition (e.g. reticulocyte count > 3%). 9. Planned surgery during the 15 days post dosing. 10. Haemoglobin pre-dose value lower than 2.0 g/dL below the lower limit of the laboratory normal range for gender and age. 11. History of splenectomy. 12. Known current malignancy (except basal cell carcinoma). 13. Received other investigational agent within 3 months prior to enrolment. 14. Positive DAT (direct Coombs-test) at screening unless subject has received treatment with IVIg or anti-D products within 3 months prior to screening with prior negative DAT. 15. Known non-responders to most recent anti-D treatment (despite any initial response to treatment). 16. Any other current treatment for ITP except corticosteroids (Prednisone or Dexamethasone) at doses equivalent to ≤30 mg prednisone/day if the daily dose has been constant for 2 weeks or more before trial drug administration. 17. Therapy with IVIg within 2 weeks prior to enrolment or with anti-D or any other treatment of ITP within 4 weeks prior to enrolment. 18. Therapy with tranexamic acid, alkylating agents or any anti-CD20 antibodies within 8 weeks prior to enrolment. 19. Any antithrombotic treatment (except acetyl salicylic acid at doses up to 150 mg daily) within 7 days prior to pre-dosing visit or planned during the trial. 20. PT/INR and aPTT out of normal range at the pre-dose visit. 21. History of venous or arterial thrombosis or known thrombophilia. 22. Diseases other than ITP that may influence the result of the trial as judged by the Investigator. 23. Creatinine 25% or more above normal range value, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) 100% above normal range value, and albumin 25% or more below normal range value. 24. Current or planned treatment with erythropoietin. 25. Subject is pregnant, breast feeding or intends to become pregnant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of AEs, including SAEs and Adverse Events of Special Interest (AESIs)Timepoint: during the 6-week trial period | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety Endpoints: 1. Maximum fall in Haemoglobin from baseline and until day 7 after administration of Sym001. 2. Acute infusion related reactions (41). 3. Presence of anti-Sym001 antibodies at pre-dose, 15 and 28 days and at 6 weeks. 4. Change from baseline in: interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor α (TNF α) at 30 minutes, 2, 8, 24, 48 and 72 hours and at day 7. 5. Clinically relevant changes in laboratory parameters, ECGs and vital signs. 6. Complement activation at 5-8 hours and 7 days post dosing. Efficacy Endpoints: 1. Percentage of subjects with platelet count > 30,000/mm3 and increase in platelet count by > 20,000/mm3 from baseline at 72 hours (major efficacy endpoint), 7 and 15 days. 2. Percentage of subjects, at 24, 48 and 72 hours, at 7, 15, and 28 days and at 6-weeks, with platelet count: a. ≥ 50,000/mm3 b. ≥ 30,000/mm3 c. Increase of > 20,000/mm3 from baseline. 3. Change of platelet count at 24, 48, 72 hours, 7, 15, 28 days and 6 weeks from baseline. 4. Time to platelet count: a. ≥ 50,000/mm3 b. ≥ 30,000/mm3 c. Increase of > 20,000/mm3 from baseline 5. Number of days with platelet count: a. ≥ 30,000/mm3 and increase of > 20,000/mm3 from baseline b. ≥ 50,000/mm3 c. ≥ 30,000/mm3 d. Increase of > 20,000/mm3 from baseline. 6. AUC for platelet count from baseline to 6-weeks. 7. Change in WHO bleeding scale from baseline (42). 8. Percentage of subjects requiring Rescue Medication. 9. PK parameters (AUC, Cmax, Cmin, T½) for Sym001. Binding of Sym001 to RBCs: DAT at screening, 24 hours, 28 days and 6-weeks post dosing. Timepoint: Varying timepoints for different endpoints. | — |
Countries
Austria, Belgium, Germany, Greece, India, Israel, Poland, Serbia, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactMr Subramanian
Project Manager
Outcome results
None listed