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

NCT01609595 | Completed Phase 2 DMC

• 2 other identifiers: ST20-P2THQK-1001-Thal P2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Beta Thalassemia Intermedia

Keywords

Thalassemia; Anemia; Fetal hemoglobin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (1)

Treatment

EXPERIMENTAL

Study drug treatment

Drug: sodium 2,2 dimethylbutyrate

Interventions

sodium 2,2 dimethylbutyrate DRUG

Oral capsule, dose 20 mg/kg/day, daily, for 26 weeks

Also known as: HQK-1001, ST20

Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of Beta Thalassemia Intermedia
• Splenectomized
• Average of two Hgb levels between 6.0 and 9.0 g/dl

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston University: lead
• Mahidol University: collaborator

Study Sites (1)

Mahidol University Thalassemia Research Centre

Nakhonpathom, Thailand

Location

Related Publications (2)

• 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.

  PMID: 20712788 BACKGROUND

• 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.

  PMID: 21422239 BACKGROUND

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia; Anemia

Interventions

2,2-dimethylbutyric acid

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Suthat Fuchareon, MD

  Thalassemia Research Centre, Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: April 25, 2012
• First Posted: June 1, 2012
• Study Start: March 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 13, 2013

Record last verified: 2013-03

Locations

TH (1)