Details

Details

Title Safety, efficacy, tolerability, pharmacokinetics and pharmacodynamics of open-label study with multiple and (for non-responders) escalating subcutaneous doses of BI 655064 once a week in patients with chronic primary immune thrombocytopenic purpura

IRB BIP1Z14

CC 15-042

Hospital Main Campus

Phase Phase 1

Disease Chronic Immune Thrombocytopenic Purpura

Drug BI655064

Description

Description

OBJECTIVES
  • The aim of this study is to evaluate the safety and the efficacy of BI 655064 administered subcutaneously to ITP patients. All patients start with 120 mg q1w for four weeks. Patients who show an increase in platelet count above or equal to 100 x 109/L will continue treatment with 120 mg q1w for additional 8 weeks. Patients whose platelet count stays below 100 x 109/L will continue treatment for 2 weeks with 180 mg q1w followed by 120 mg q1w for additional 6 weeks. After last dose of BI 655064, there will be a 12 weeks follow-up for all patients.
  • The study will evaluate response after the 12 weeks of treatment, which is defined as increase in thrombocytes by greater than 20 x 109/L from baseline and above 50 x 109/L, both at any time point between week 1 and 12 with no rescue therapy.
  • In addition, the study will evaluate exploratory pharmacodynamic parameters (anti-platelet GP-IIb/IIIa, Ib/IX and Ia/IIa antibodies), receptor occupancy, and the population pharmacokinetics of BI 655064.
Inclusion Criteria

Inclusion Criteria

  1. Male and female patients with persistent or chronic primary ITP, diagnosed according to the American Society of Hematology guidelines (P12-03913).
  2. Male and female patients aged ≥18
  3. Platelet count >10 x 109/L (10,000/mm3) and < 50 x 109/L (50,000/mm3) at visit 1
  4. Patients who have signed and dated a written informed consent by date of Visit 1 in accordance with Good Clinical Practices (GCP) and local legislation.
Exclusion Criteria

Exclusion Criteria

  1. Any other treatment for ITP except glucocorticoids with an equivalent dose of ≤ 20 mg prednisolone and stable for at least 2 weeks prior to screening.
  2. No treatment with thrombopoetin agonists for at least 1 week prior to screening. Patients who are on stable dose of thrombopoetin agonists for at least 4 weeks prior to screening can remain on them and still enter study
  3. No treatment with ANTI-CD20 antibodies for at least 6 months prior to screening.
  4. No treatment with immunosuppressants for at least 2 weeks prior to screening. Patients who are on a stable dose of immmunosuppressants for at least 4 weeks prior to screening can remain on them and still enter the study.
  5. Any concurrent disease if clinically significant based on the investigators medical assessment.
  6. Any acute infection at screening or baseline. Re-screening after 30 days is allowed.
  7. History of malignancy in the past 5 years except cured squamous cell or basal cell carcinoma.
  8. Positive test for HCV, HBs antigen, HIV infection at screening.
  9. Any history of lymphoproliferative disorders, myelodysplasia, systemic lupus erythematosus, drug-inducedthrombocytopenia. History of clinically significant hypoglobulinemia or dysglobulinemia in the previous year before screening
  10. Patients participating in another trial with an investigational drug within 30 days or five half-lives of the drug whichever is longer prior to screening.
  11. History of alcohol (more than 30g per day) or drug abuse within one year prior to screening.
  12. Leukocyte count < 2.5 x 10 9 /L (2500/mm3), neutrophil count <1.0 x 109/L(1000/mm3), lymphocyte count < 0.75 x10/9L (750/mm3), hemoglobin 100 g/L (10 g/dL), and transaminase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) > 2 times the upper limit of normal at visit 1. Re-screening after 30 days is allowed.
  13. Any abnormal laboratory values at screening (except low platelet count) if clinically significant based on the investigators medical assessment.
  14. Clinically significant abnormalities in ECG based on the investigators medical assessment.
  15. Pre-menopausal women (last menstruation ≤ one year prior to informed consent) who: are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomized partner. NOTE: Female patients taking stable doses of estrogens or other hormonal replacement therapy will be included if the patient has been on these agents for at least three months prior to study entry. Female subjects who are not of childbearing potential due to being postmenopausal (2 years without menstruation) or surgical sterilization (oophorectomy [removal of the ovaries], hysterectomy [removal of the uterus] and/or tubal ligation [tubes tied]), do not need to use birth control to be eligible to take part in this research study.