A Study of HQK-1001 in Patients With Sickle Cell Disease

A Randomized, Open-Label, Multi-Dose Study of HQK-1001 in Subjects With Sickle Cell Disease

The purpose of this study is to evaluate the safety and tolerability of three dose levels of HQK-1001 administered once daily for 26 weeks in subjects with sickle cell disease.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Sickle Cell Anemia; Sickle Cell Disorders; Hemoglobin S Disease; Sickling Disorder Due to Hemoglobin S
• Intervention / Treatment: Drug: HQK-1001

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, MSG 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, MSG 2C4
      • University Health Network Toronto General Hospital
• Egypt
  • Cairo, Egypt
    • Abu El Reesh Pediatric University Hospital
• Jamaica
  • Kingston
    • Mona, Kingston, Jamaica
      • University of the West Indies - Sickle Cell Unit
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center
  • Beirut, Lebanon
    • Rafik Hariri University Hospital
  • Hazmieh, Lebanon
    • Chronic Care Center
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center - Oakland
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Miller School of Medicine - Dept of Pediatrics
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University - Adult SIckle Cell Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago - Dept of Pediatrics
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center - Feist Weiller Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill - Comprehensive Sickle Cell Program
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9063
      • Univerisity of Texas Southwestern Medical Center at Dallas - Pediatric Hematology Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Established diagnosis of SCD
• Males and females between 12 and 60 years of age, inclusive
• At least 3 episodes of a SCD-related crisis or complication in the 3 years prior to screening OR 1 episode of acute chest syndrome in the 5 years prior to screening
• If receiving hydroxyurea, must be receiving a stable dose for at least 6 months prior to screening
• If hydroxyurea treatment has been discontinued, at least 3 months have elapsed since last dose
• If transfusion in the 4 months prior to screening, then HbA level < 20% at screening
• Average of the initial two HbF levels ≥ 2.0 % within ≤ 7 days prior to the initial dose of HQK-1001. The two must be obtained ≥ 24 hours apart
• Ability to swallow tablets
• Able and willing to give informed consent and assent (if applicable)
• If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 7 days of first dose of HQK-1001
• If a subject is a WCBP, she must agree to use an effective form of contraception within 7 days of the initial dose of HQK-1001 and for one month after HQK-1001 discontinuation
• Sexually active male subjects (with WCBP partners) must agree to use latex condoms or ensure that their partner(s) use an effective form of contraception
• In the view of the Investigator, subject is able and willing to comply with necessary study procedures

Exclusion Criteria:

• More than 4 hospitalizations for acute sickle cell related events in the previous 12 months prior to screening
• Pulmonary hypertension requiring oxygen therapy
• QTc > 450 msec (male) or 470 msec (female) on screening ECG (QT corrected by Fridericia's formula)
• Assigned to a regular transfusion program
• Use of erythropoiesis stimulating agents within 90 days of screening
• ALT > 3x upper limit of normal (ULN)
• Serum creatinine > 1.2 mg/dL
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• An acute vaso-occlusive event within 3 weeks prior to screening
• Creatine phosphokinase (CK) > 20% above the ULN
• An acute illness (e.g., febrile, GI, respiratory) within 72 hours prior to screening
• History of syncope, clinically significant dysrhythmias or resuscitation from sudden death
• Chronic opiate use, which, in the view of the Investigator, could confound evaluation of an investigational drug
• Current abuse of alcohol or drugs
• Received another investigational agent within 4 weeks or 5 half-lives, whichever is longer, prior to screening
• Currently pregnant or breast feeding a child
• Known infection with HIV-1
• Infection with hepatitis B or hepatitis C, such that patients are currently on therapy or will be placed on therapy during the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HQK-1001 (30 mg/kg)	Drug: HQK-1001; HQK-1001 tablets, once daily for daily 26 weeks
Experimental: HQK-1001 (40 mg/kg)	Drug: HQK-1001; HQK-1001 tablets, once daily for daily 26 weeks
Experimental: HQK-1001 (50 mg/kg)	Drug: HQK-1001; HQK-1001 tablets, once daily for daily 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Physical exams, vital signs, clinical laboratory safety assessments, ECG and adverse event monitoring.	Day 1 through Week 30

Secondary Outcome Measures

Outcome Measure	Time Frame
Fetal hemoglobin levels	Day 1 and Weeks 4, 8, 12, 16, 20, 25, 26 and 30
Incidence of sickle cell crisis events	Day 1 through Week 30

Collaborators and Investigators

• Sponsor: HemaQuest Pharmaceuticals Inc.

Publications and helpful links

General Publications

• Kutlar A, Reid ME, Inati A, Taher AT, Abboud MR, El-Beshlawy A, Buchanan GR, Smith H, Ataga KI, Perrine SP, Ghalie RG. A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Am J Hematol. 2013 Nov;88(11):E255-60. doi: 10.1002/ajh.23533. Epub 2013 Oct 3.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimate): March 24, 2011

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 11, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Disease; Anemia, Sickle Cell; Sickle Cell Trait
• Other Study ID Numbers: HQP 1001-SCD-006