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.

Phase 2

Completed

Conditions: Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects

Registration Number: CTRI/2010/091/003049

Lead Sponsor: Symphogen AS

Brief Summary: Immune Thrombocytopenic Purpura (ITP): ITP is an autoimmune disease mediated by anti-platelet autoantibodies that cause opsonisation and platelet elimination through binding to FcÎ³R-bearing phagocytic cells in the Reticuloendothelial System (RES) and especially in the spleen, leading to a reduced platelet count (thrombocytopenia). ITP is a primary form of immune thrombocytopenia where typically no aetiology can be found. Thrombocytopenia is defined by platelet counts < 150,000/mm3 and is characterized clinically by increased bruising tendency. However, ITP often presents as spontaneous bleeding in individuals with platelet counts of less than 20,000/mm3. Subjects with platelet counts < 10,000/mm3 may present with severe cutaneous bleedings, gingival bleeding, epistaxis, haematuria or menorrhagia. Spontaneous intracranial bleeding and other spontaneous internal bleeding can be seen in severe thrombocytopenia with platelet counts below 5,000/mm3 (2). ITP in individuals with platelet counts above 30,000/mm3 is most often diagnosed incidentally after a routine complete blood cell count. Some bleeding risk is present in subjects with platelet counts between 30,000/mm3 and 50,000/mm3 depending on the coexisting factors for bleeding (3). ITP is also characterized by an increased proportion of immature peripheral platelets, and to some extent by an increased proportion of megakaryocytes in the bone marrow. This is 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.? Sym001 is a clear colourless sterile liquid for injection filled into 10 mL glass injection vials with a bromobutyl rubber stopper. The vials are sealed with aluminium caps. The Sym001 drug product contains 0.6 mg/mL of Sym001 recombinant human anti-RhD IgG in citrate-phosphate buffer, sodium chloride and polysorbate 20, pH 6.0. The active ingredient in Sym001 is a mixture of 25 anti-RhD antibodies produced by expression in recombinant Chinese Hamster Ovary (CHO) cells. This is a global clinical trial and the participating countries are:- Germany, Belgium, U.K, Serbia, Poland, Spain, Romania, Russia, Ukraine, Israel, India, US, Australia. A maximum of 66 RhD positive, non-splenectomized ITP patients would be enrolled globally and it will be a Competitive Recruitment. A total of 20 subjects would be recruited from India. Patient recruitment in India is expected to start from 15-Feb-2011.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 66

Inclusion Criteria

Informed consent obtained before any trial-related procedures.
Confirmed presence of thrombocytopenia with platelet count < 30,000/mm3 at the pre-dose visit.
In each cohort < 200 Î¼g/kg a maximum of 3 subjects will be included with platelet counts < 10,000/mm3, and in cohorts > 200 Î¼g/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 and within > 1 hour interval between each other and both being < 30,000/mm3 will be used to confirm thrombocytopenia.
History of isolated ITP (thrombocytopenia with no known aetiology, blood smear showing normal appearing platelets or if performed, a bone marrow showing adequate thrombopoÃ¯esis and normal erythroid and myeloid morphology).
RhD- positive serology.
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 â‰¥30,000/mm3.
If female and of child-bearing potential, subject has a negative pregnancy test at screening.
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

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.
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).
History of abnormal bone marrow examination (except ITP-typical megacaryocytosis).
At pre-dose visit: an ongoing haemorrhage corresponding to a grade 3 or 4 on the WHO bleeding scale.
Current immune haemolytic anaemia.
Underlying haemolytic condition (e.g. reticulocyte count > 3%).
Planned surgery during the 15 days post dosing.
Haemoglobin pre-dose value lower than 2.0 g/dL below the lower limit of the laboratory normal range for gender and age.
History of splenectomy.
Known current malignancy (except basal cell carcinoma).
Received other investigational agent within 3 months prior to enrolment.
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.
Known non-responders to most recent anti-D treatment (despite any initial response to treatment).
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.
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.
Therapy with tranexamic acid, alkylating agents or any anti-CD20 antibodies within 8 weeks prior to enrolment.
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.
History of venous or arterial thrombosis or known thrombophilia.
Diseases other than ITP that may influence the result of the trial as judged by the Investigator.
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.
Current or planned treatment with erythropoietin.
Subject is pregnant, breast feeding or intends to become pregnant.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence and severity of AEs, including SAEs and Adverse Events of Special Interest (AESIs)	during the 6-week trial period

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): Apollo Hospital, Hyderabad
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Hyderabad, ANDHRA PRADESH, India
Columbia Asia Hospital
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Bangalore, KARNATAKA, India
Kasturba Medical College Hospital
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College, (KMC),, India
M S Ramaiah Hospital, Bangalore
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Bangalore, KARNATAKA, India
Medanta Cancer Hospital, Gurgoan
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Gurgaon, HARYANA, India
Narayana Hrudayalaya Hospital,
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Bangalore, KARNATAKA, India
St. Johns Medical College Hospital, Bangalore
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Bangalore, KARNATAKA, India
Apollo Hospital, Hyderabad
🇮🇳Hyderabad, ANDHRA PRADESH, India
Dr SVSSPrasad
Principal investigator
040-23431725
cvpr01@aherf-smo.org