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Study of SDMB (2,2 Dimethylbutyrate, Sodium Salt) in Beta Thalassemia Intermedia in Thailand

Phase 2
Completed
Conditions
Beta Thalassemia Intermedia
Interventions
Drug: sodium 2,2 dimethylbutyrate
Registration Number
NCT01609595
Lead Sponsor
Boston University
Brief Summary

Beta thalassemia intermedia is an inherited blood disease caused by molecular mutations which reduce the beta globin protein chain of adult hemoglobin A, the protein in red blood cells which carries oxygen throughout the body. Beta thalassemias cause progressively severe anemia, widespread organ damage, and often require blood transfusions. There is no FDA approved therapeutic to treat the underlying cause of beta thalassemia. Fetal hemoglobin is another type of endogenous hemoglobin which can replace the reduced beta globin protein, reduce the anemia, and even abolish transfusion requirements. This type of hemoglobin is normally suppressed in infancy.

Sodium 2,2 dimethylbutyrate (ST20, or HQK-1001) is a small molecule which stimulates production of fetal hemoglobin in nonhuman primates and in human patients in Phase I/II trials.

This is a Phase 2 open-label trial to evaluate the ability of this oral therapeutic to reduce anemia in patients with beta thalassemia intermedia, when administered once daily for 26 weeks. All participants will receive the study drug.

Detailed Description

This trial will:

1. Determine the proportion of patients in which treatment with the study drug results in an increase in total hemoglobin by 1.5 g/dl above baseline levels when administered for 26 weeks in Thai patients with beta thalassemia intermedia, including Hemoglobin E beta thalassemia.

2. Determine the number and proportion of participants in whom treatment with the study drug results in an increase in fetal hemoglobin.

3. Determine the number of participants who have adverse events.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria
  • Diagnosis of Beta Thalassemia Intermedia
  • Splenectomized
  • Average of two Hgb levels between 6.0 and 9.0 g/dl
Exclusion Criteria
  • Red blood cell transfusion within 3 months of study drug initiation
  • Enlarged spleen
  • Use of hydroxyurea within 6 months
  • QT Segment corrected (QTc)> 450 msec (men) or 470 msec (women) on screening ECG
  • Use of iron chelating agents within 7 days of first dose
  • Alanine Transaminase(ALT)> 4 times the upper limit of normal
  • Use of erythropoiesis stimulating agents (ESAs) within 90 days of first dose
  • serum creatinine > 1.5 mg/dL

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatmentsodium 2,2 dimethylbutyrateStudy drug treatment
Primary Outcome Measures
NameTimeMethod
The number of participants in which an increase in total hemoglobin of at least 1.5 g/dl above average baseline occurs with study drug treatment.Within 30 weeks, including 26 weeks of dosing with the study drug

Baseline hemoglobin levels will be determined by averaging 2 values prior to administration of the study drug.

The number of participants in which an increase in total hemoglobin of at least 1.5 g/dL above baseline occurs will be determined.

Secondary Outcome Measures
NameTimeMethod
The proportion of participants in which an increase in fetal hemoglobin occurs above the subjects' averaged baseline levels.Within 30 weeks, including 26 weeks of study drug administration

Tests of fetal hemoglobin will be obtained at two times prior to administration of the study drug and will be averaged. Laboratory tests of fetal hemoglobin will be assessed monthly during the study drug administration for 26 weeks, as a biomarker of drug activity.

Trial Locations

Locations (1)

Mahidol University Thalassemia Research Centre

🇹🇭

Nakhonpathom, Thailand

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