An open label extension study to evaluate the safety of long term dosing of AMG 531 in trombocytopenic subjects with myelodysplastic syndromes (MDS).

Title of the study:
An Open Label Extension Study Evaluating the Safety of Long Term Dosing of AMG
531 in Thrombocytopenic Subjects with Myelodysplastic Syndromes (MDS)

Background of the study:
Myelodysplastic syndrome (MDS)is a heterogenous group of clonal disorders in
the hematopoetic stem cell characterised by a varying degree of cytopenia in
one or more cell lines. Prognosis can be expressed by the International
Prognostic Scoring System (IPSS) score. Patients with low or intermediary-1
risk according to the IPSS are often treated with supportive care. About 30% of
these patients have trombocytopenia at presentation, in the others it develops
during the course of the disease. Thrombocytopenia can give rise to bleeding,
often of the oral mucosa, and spontaneous hematomas. This negatively affects
the quality of life of these patients. Thrombocyte transfusions are only
effective for a few days and are given only in case of serious bleeding. Other
than a thrombocyte transfusion, a thrombocytopenia cannot be treated at the
moment. AMG 531 is a recombinantly expressed protein in E. Coli which offers a
possible new treatment for thrombocytopenia in MDS patients.

To provide long-term safety data for the use of AMG 531 in thrombocytopenic
subjects with IPSS low or intermediate-1 risk MDS.

This is an open label extension study. Patients who have participated in the
AMG 531 20050159 or 20060198 study and fulfil the protocol specified in- and
exclusion criteria are allowed to participate in this open label extension
study.
Patients will enter the screening when patients have signed and dated the
Informed Consent Form. If patients meet the participation criteria, the
treatment phase will start. In this period, the actual treatment with AMG 531
takes place. It will last at most until June 2009. Patients will visit the
hospital weekly during this treatment phase. Patients will need to return one
week and four weeks after their last administration of AMG 531 to close the
study.

QW or Q2W Injections with AMG 531

Patients will visit the hospital every week. At the first and last visit, a
bone marrow aspirate and biopsy will be done. Physical examination and
laboratory evaluations will be regularly done. At the first visit, a pregnancy
test, if applicable, will be done.
AMG 531 has been studied in 2 phase 1 studies in healthy volunteers and 2 phase
2 studies in ITP patients. There is also an ongoing open label extension study
in patients with ITP. To date no neutralizing antibodies to endogenous TPO have
been detected. In healthy volunteers the most common adverse events were
headache, fatigue and flu-like symptoms. In ITP patients these were headache,
fatigue and epistaxis. In patients with ITP an increase of bone marrow
reticulin was reported.