Effects of HQK-1001 in Patients With Sickle Cell Disease

A Randomized, Placebo-controlled, Phase 2 Study of HQK-1001 in Sickle Cell Disease

The purpose of this study is to evaluate the effects of HQK-1001 on Hb F in subjects with sickle cell disease.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • University Health Network Toronto General Hospital
• Egypt
  • Cairo, Egypt
    • Abu El Reesh Pediatric University Hospital
  • Cairo, Egypt
    • Ain Sham University Hospital
• Jamaica
  • Mona, Kingston 7, Jamaica
    • University of the West Indies
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center
  • Beirut, Lebanon
    • Rafik Hariri University Hospital
  • Beirut, Lebanon
    • Chronic Care Center
• United States
  • Alabama
    • Mobile, Alabama, United States, 36617-2238
      • University of South Alabama
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center - Oakland
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University Hospital
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • The Children's Hospital at Montefiore Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth Univeristy - Center on Health Disparities

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females between 12 and 60 years of age
• Diagnosis of SCD, type Hb SS or Hb S-B0 Thalassemia
• At least 1 episode of SCD pain crisis, acute chest syndrome, other acute SCD complications, or leg ulcers in the 12 months prior to screening
• Not being treated with Hydroxyurea (HU); if HU treatment has been previously administered and then discontinued, at least 3 months must have elapsed since last dose of HU
• If subject has been transfused in the 3 months prior to screening, then Hb A level < 20% at screening
• Baseline Hb F level obtained within 14 days prior to randomization
• Able to swallow tablets
• Able and willing to give informed consent and/or assent
• If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 14 days of first dose of HQK-1001 and a negative urine pregnancy test prior to dosing on Day 1
• If a subject is a WCBP, she must agree to use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation
• Sexually active male subjects who have not had a vasectomy must agree to use latex condoms with WCBP partners or ensure that their partner(s) use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation.

Exclusion Criteria:

• Assigned to a regular transfusion program
• Use of erythropoiesis stimulating agents within 90 days prior to screening
• An SCD pain crisis or SCD-related acute complication within 3 weeks prior to randomization
• More than 5 SCD pain crisis or SCD-related acute complications within 12 months prior to screening
• Pulmonary hypertension requiring therapy
• ALT or AST > 3x ULN
• Serum creatinine > 1.5x ULN
• Serum amylase levels > 1.5x ULN
• Serum lipase level > 1.5x ULN
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• 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 due to SCD-related complication
• Symptomatic peptic ulcer, hiatus hernia, or gastroesophageal reflux disease (GERD)
• History of pancreatitis
• Chronic opiate use, which, in the view of the investigator, could confound evaluation of an investigational drug
• Current abuse of alcohol or drugs
• Use of 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 subjects are currently on anti-viral therapy or will be placed on therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo tablets, twice daily for 48 weeks
ACTIVE_COMPARATOR: HQK-1001	Drug: HQK-1001; HQK-1001 tablets, twice daily for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in % fetal hemoglobin	Day 1 through Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and number of SCD pain crises and SCD-related complications		Day 1 through Week 52
Subject reported daily pain scale scores and analgesic use		7 consecutive days following clinic visits at Day 1, and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Change in FACIT Fatigue Scale results		Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments		Day 1 through Week 52
HQK-1001 pharmacokinetic parameters	A subset of subjects (7) will undergo sampling for detailed analysis of pharmacokinetic parameters (AUC, Cmax) with samples taken pre-dose, and 1, 2, 4, 8, and 10 hours after the morning dose at Week 4.	1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48

Collaborators and Investigators

• Sponsor: HemaQuest Pharmaceuticals Inc.

Publications and helpful links

General Publications

• Reid ME, El Beshlawy A, Inati A, Kutlar A, Abboud MR, Haynes J Jr, Ward R, Sharon B, Taher AT, Smith W, Manwani D, Ghalie RG. A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Am J Hematol. 2014 Jul;89(7):709-13. doi: 10.1002/ajh.23725. Epub 2014 Apr 15.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: May 12, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (ESTIMATE): May 18, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

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-007