A multi-centre, single intravenous dose, exploratory dose-finding, open label trial on the safety and efficacy of Sym001 in the treatment of Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects - N/A

Conditions: Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects
MedDRA version: 9.1Level: LLTClassification code 10043561Term: Thrombocytopenic purpura

Registration Number: EUCTR2007-006081-15-DE

Lead Sponsor: Symphogen A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 66

Inclusion Criteria

Informed consent obtained before any trial-related procedures.
2.Age >18 years.
3.Confirmed presence of thrombocytopenia with platelet count < 30,000/mm3 at the pre-dose visit. In each cohort< 200 µg/kg a maximum of 3 subjects will be included with platelet counts < 10,000/mm3, and in cohorts > 200 µg/kg a maximum of 1 subject with platelet counts < 10,000/mm3 will be included in order to limit variability. Two individual pre-dose platelet counts taken on the dosing day within > 1 hour interval between each other and both being < 30,000/mm3 will be used to confirm thrombocytopenia.
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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 test 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 enrollment 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 know 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 (according to the local laboratory) at pre-dose visit.
24.Current or planned treatment with erythropoietin.
25.Subject is pregnant, breast feeding or intends to become pregnant.
26.Previous dosing with Sym001 in this trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of Sym001 following a single intravenous dose, at multiple dose levels, in the treatment of ITP in RhD positive, non-splenectomized adult subjects;Secondary Objective: To evaluate the efficacy of Sym001 following a single intravenous dose in the treatment of ITP in RhD positive, non-splenectomized adult subjects.<br>•To evaluate the binding of Sym001 to RBCs following a single intravenous dose of Sym001 in the treatment of ITP in RhD positive, non-splenectomized adult subjects.<br>•To evaluate an appropriate dose of Sym001 for Phase 3.<br>;Primary end point(s): Incidence and severity of AEs, including SAEs and Adverse Events of Special Interest (AESIs) during the 6-week trial period.<br>

Secondary Outcome Measures

Name	Time	Method

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