Study of SDMB (2,2 Dimethylbutyrate, Sodium Salt) in Beta Thalassemia Intermedia in Thailand (ST20-P2T)

An Open Label Academic Phase 2 Study of SDMB in Subjects in Thailand With Beta Thalassemia Intermedia

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.

Study Overview

• Status: Completed
• Conditions: Beta Thalassemia Intermedia
• Intervention / Treatment: Drug: sodium 2,2 dimethylbutyrate

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Nakhonpathom, Thailand
    • Mahidol University Thalassemia Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment; Study drug treatment	Drug: sodium 2,2 dimethylbutyrate; Oral capsule, dose 20 mg/kg/day, daily, for 26 weeks; Other Names: HQK-1001, ST20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Within 30 weeks, including 26 weeks of dosing with the study drug

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: Mahidol University
• Investigators: Principal Investigator: Suthat Fuchareon, MD, Thalassemia Research Centre, Mahidol University

Publications and helpful links

General Publications

• Perrine SP, Castaneda SA, Chui DH, Faller DV, Berenson RJ, Siritanaratku N, Fucharoen S. Fetal globin gene inducers: novel agents and new potential. Ann N Y Acad Sci. 2010 Aug;1202:158-64. doi: 10.1111/j.1749-6632.2010.05593.x.
• Perrine SP, Wargin WA, Boosalis MS, Wallis WJ, Case S, Keefer JR, Faller DV, Welch WC, Berenson RJ. Evaluation of safety and pharmacokinetics of sodium 2,2 dimethylbutyrate, a novel short chain fatty acid derivative, in a phase 1, double-blind, placebo-controlled, single-dose, and repeat-dose studies in healthy volunteers. J Clin Pharmacol. 2011 Aug;51(8):1186-94. doi: 10.1177/0091270010379810. Epub 2011 Mar 21.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (ESTIMATE): June 1, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 13, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Anemia; Thalassemia; Fetal hemoglobin
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: ST20-P2T; HQK-1001-Thal P2 (OTHER: HemaQuest)