Phase I Study Evaluating TXA127 in Low/Intermediate-1 Risk Myelodysplastic Syndrome and Thrombocytopenia
Phase 1, single-center, open-label, sequential cohort dose escalation study. This is a 3 + 3 design study involving at least 3 subjects in ascending dose cohorts, with subjects participating up to 10 weeks.
The overall study objectives are to evaluate the safety and tolerability of TXA127 in thrombocytopenic subjects with low or intermediate-1 risk MDS.
Evaluation of the platelet response and the erythroid and granulocytic responses to TXA127 will provide preliminary efficacy data.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Open-Label Dose-Escalating Study Evaluating the Safety and Preliminary Efficacy of TXA127 in Patients With Low/Intermediate-1 Risk Myelodysplastic Syndrome and Thrombocytopenia|
- Safety and tolerability (changes from baseline for safety parameters) of TXA127 in thrombocytopenic subjects with low or Intermediate-1 risk myelodysplastic syndrome (MDS). [ Time Frame: Once or twice weekly during treatment and at follow-up visits. (up to 2 years) ] [ Designated as safety issue: Yes ]
Evaluations performed during the study include vital signs and physical exam at all visits (twice/week for 4 weeks of treatment and at follow-up visits occurring 2 & 4 weeks following last treatment), blood chemistry, CBC, and platelet counts (once per week for 4 weeks, and at follow-up visits), concomitant medication and adverse event evaluations throughout the study period (8 weeks).
Safety and tolerability will be assessed by incidence, severity, and changes from baseline of all relevant parameters including adverse events (AEs), laboratory values, and vital signs
- Evaluate the platelet response (change in platelet count from baseline) of thrombocytopenic subjects with low or intermediate-1 risk MDS receiving TXA127. [ Time Frame: Twice Weekly during treatment and at follow-up visits (up to 2 years) ] [ Designated as safety issue: Yes ]Platelet counts and response will be evaluated twice per week at clinic visits during the treatment period (4 weeks), and again at the follow-up visits (week 6 and week 8).
- Assess the erythroid and granulocytic response (change from baseline) to TXA127 in patients with low or intermediate-1 risk MDS. [ Time Frame: Weekly during treatment and at follow-up visits (up to 2 years) ] [ Designated as safety issue: Yes ]Erythroid and granulocytic responses will be evaluated once weekly during the treatment period (first visit of each treatment week), and again at the follow-up clinic visits.
|Study Start Date:||April 2011|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: TXA127 sc injectable
All cohorts will recieve TXA127; Cohorts receive either 300, 600, or 900 ug/kg daily
Cohorts in this study will receive 300, 600, or 900 ug/kg daily by subcutaneous injection
Other Name: Angiotensin 1-7
The hematopoietic properties demonstrated in the preclinical and clinical studies support the investigation of TXA127 to stimulate stem cell and progenitor cell proliferation. This is an exploratory study in a limited population of low or intermediate-1 MDS subjects who have platelet counts of ≤50 x 109/L to evaluate the effects of TXA127 on platelet response and on granulocytic and erythroid response.
Platelet response will be defined as complete and major as below:
- Complete platelet response: increase of platelet count to >100 x 109/L
- Major platelet response: increase of absolute platelet count by >30 x 109/L Other responses will be according to modified IWG MDS criteria (2006). Daily subcutaneous dosing of TXA will be carried out both in the clinic at scheduled visits and at home between clinic visits for a period fo 28 days.
|United States, Texas|
|MD Anderson Leukemia Department|
|Houston, Texas, United States, 77230-1402|
|Study Chair:||Gere S diZerega, MD||Sponsor - US Biotest Inc,|