Trial of HQK-1001 in Beta Thalassemia Intermedia in Lebanon

NCT01642758 | Completed Phase 2 DMC

• 1 other identifier: HQK-P2-THAL
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Beta thalassemia intermedia syndromes are genetic anemias caused by mutations which reduce production of beta globin, a major component of adult hemoglobin A, the protein which delivers oxygen throughout the body. Patients suffer from poor growth, fatigue, heart failure, endocrine deficiencies, and eventually, many require chronic blood transfusions. There is no approved therapeutic for the deficiency of beta globin chains in beta thalassemia. This trial will study an oral therapeutic which stimulates production of fetal globin, an alternate type which is produced by all humans, but is normally switched off in infancy. This type of globin can compensate for the missing protein in beta thalassemia.

Conditions

Beta Thalassemia Intermedia

Keywords

Thalassemia intermedia; Fetal hemoglobin; Hemoglobin

Outcome Measures

Primary Outcomes (1)

• To measure changes from baseline in total hemoglobin when HQK-1001 is administered orally for 26 weeks in subjects with beta thalassemia intermedia.

  Baseline hemoglobin levels will be determined in each subject and averaged from levels obtained on a screening visit and on day one of the study, before any drug is taken. Hemoglobin levels will then be analyzed every 4 weeks during 26 weeks of taking the study drug and for 4 weeks after the dosing is completed. Changes from baseline will be determined.

  6 months

Secondary Outcomes (2)

• To measure the number of adverse events which occur with HQK-1001 treatment when given over 26 weeks in beta thalassemia intermedia.

  6 months

• To measure changes from baseline in HbF during treatment with HQK-1001 for 26 weeks in beta thalassemia intermedia.

  6 months

Study Arms (1)

Sodium 2,2 dimethylbutyrate

EXPERIMENTAL

A single dose (20 mg/kg/day) of study drug will be taken once per day by mouth.

Drug: Sodium 2,2 dimethylbutyrate

Interventions

Sodium 2,2 dimethylbutyrate DRUG

Oral capsules, dose 20 mg/kg/day, once per day for 26 weeks

Also known as: ST20

Sodium 2,2 dimethylbutyrate

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of beta thalassemia intermedia
• Ages 16-50 years
• Average total Hgb levels between 6.0 and 9.0 gm/dl within 30 days of initial dose of study drug
• Able to comply with all study procedures
• If female and of childbearing potential, must have a documented negative pregnancy test prior to entry and every 4 weeks

You may not qualify if:

• Red blood cell transfusions within 3 months prior to administration of study drug
• QT Segment corrected (QTc)\> 450 msec
• Use of Erythropoiesis Stimulating Agents(ESAs)within 9 days of first dose
• Hydroxyurea treatment within 6 months of first study drug
• History of significant arrythmias, syncope, or resuscitation
• Alanine Transaminase (ALT)\> 4x upper limit of normal
• Serum creatinine \> 1.5 mg/dl
• Sse of iron chelating agents within 7 days of first dose
• Pulmonary hypertension requiring oxygen therapy

Sponsors & Collaborators

• Boston University: lead
• HemaQuest Pharmaceuticals Inc.: collaborator

Study Sites (1)

Chronic Care Center

Beirut, Lebanon

Location

Related Publications (2)

• 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

• 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

MeSH Terms

Conditions

beta-Thalassemia

Interventions

2,2-dimethylbutyric acid

Condition Hierarchy (Ancestors)

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

Study Officials

• Susan P Perrine, MD

  Boston University

  STUDY DIRECTOR

• Adlette Inati, MD

  Chronic Care Center and Rafik Hariri University Hospital, Beirut, Lebanon

  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: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 17, 2012
• Study Start: May 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: January 1, 2013
• Last Updated: March 14, 2013

Record last verified: 2013-03

Locations

LE (1)