Phase I Study Evaluating TXA127 in Low/Intermediate-1 Risk Myelodysplastic Syndrome and Thrombocytopenia

NCT01362036 | Terminated Phase 1

• 1 other identifier: TXA127-2010-003
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability (changes from baseline for safety parameters) of TXA127 in thrombocytopenic subjects with low or Intermediate-1 risk myelodysplastic syndrome (MDS).

  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

  Once or twice weekly during treatment and at follow-up visits. (up to 2 years)

Secondary Outcomes (2)

• Evaluate the platelet response (change in platelet count from baseline) of thrombocytopenic subjects with low or intermediate-1 risk MDS receiving TXA127.

  Twice Weekly during treatment and at follow-up visits (up to 2 years)

• Assess the erythroid and granulocytic response (change from baseline) to TXA127 in patients with low or intermediate-1 risk MDS.

  Weekly during treatment and at follow-up visits (up to 2 years)

Study Arms (1)

TXA127 sc injectable

EXPERIMENTAL

All cohorts will recieve TXA127; Cohorts receive either 300, 600, or 900 ug/kg daily

Drug: TXA127

Interventions

TXA127 DRUG

Cohorts in this study will receive 300, 600, or 900 ug/kg daily by subcutaneous injection

Also known as: Angiotensin 1-7

TXA127 sc injectable

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MDS using the World Health Organization classification and Low or Intermediate-1 risk MDS using the IPSS
• The mean of two platelet counts taken during the 2-week Screening Period must be ≤50 x 109/L, with no individual non-transfused count \>60 x 109/L. Platelet counts taken prior to Informed Consent may be used as one of the two counts taken within 2 weeks prior to study Day 1, but both counts must be obtained within 4 weeks of commencement of treatment.
• Subjects must be ≥18 years of age at the time of obtaining informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
• Adequate Liver Function, as evidenced by a serum bilirubin ≤2 times the laboratory upper limit of normal (ULN) (except for patients with a confirmed diagnosis of Gilbert's Disease), ALT and/or AST ≤3 times the laboratory ULN.
• A serum creatinine concentration ≤2 mg/dL

You may not qualify if:

• Currently receiving any treatment for MDS other than transfusions (last transfusion must be at least 4 weeks prior to treatment).
• If granulocyte and/or erythropoetic growth factors are currently being received, there should be a 4-week washout prior to treatment, and they may not be used during the study period.
• Concurrent active malignancy (other than controlled prostate cancer, in situ cervical cancer, or basal cell cancer of the skin)
• Prior history of bone marrow transplantation
• Unstable angina, uncontrolled congestive heart failure \[NYHA \> class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction, or a QTc interval value \>450ms.
• Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
• Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine, or mycophenolate within 4 weeks of start of treatment
• Received IL-11 (oprelvekin) within 4 weeks before screening
• Have ever previously received rTPO, PEG-rHuMGDF, eltrombopag, or romiplostim
• Less than 4 weeks since receipt of any investigational agent (not FDA approved, for any indication)
• History of arterial thrombosis (e.g., stroke or transient ischemic attack) in the past year
• History of venous thrombosis that currently requires anti-coagulation therapy
• Female subjects who are pregnant or breastfeeding. Women of childbearing potential are required to have a positive HCG serum or urine pregnancy test performed 7 days prior to first study drug dose
• Women of childbearing potential who are unwilling to use an adequate form of contraception during the course of the study.
• Subjects with current alcohol abuse, illicit drug use, or any other condition (e.g., psychiatric disorder) that, in the opinion of the Investigator, may interfere with the patient's ability to comply with the study requirements or visit schedule.

Sponsors & Collaborators

• Tarix Pharmaceuticals: lead

Study Sites (1)

MD Anderson Leukemia Department

Houston, Texas, 77230-1402, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

angiotensin I (1-7)

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gere S diZerega, MD

  Sponsor - US Biotest Inc,

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2011
• First Posted: May 27, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: August 31, 2016

Record last verified: 2016-08

Locations

US (1)