Clinical trial NCT01322269: A Study of HQK-1001 in Patients With Sickle Cell Disease
Official title: A Randomized, Open-Label, Multi-Dose Study of HQK-1001 in Subjects With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Sickle Cell Anemia
Sickle Cell Disorders
Hemoglobin S Disease
Sickling Disorder Due to Hemoglobin S
Lead sponsor: HemaQuest Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-24
Enrollment: 52
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety
timeFrame: Day 1 through Week 30
Secondary outcomes:
measure: Fetal hemoglobin levels
timeFrame: Day 1 and Weeks 4, 8, 12, 16, 20, 25, 26 and 30
measure: Incidence of sickle cell crisis events
timeFrame: Day 1 through Week 30
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center - Oakland
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine - Dept of Pediatrics
state: Florida
city: Augusta
country: United States
facility: Georgia Health Sciences University - Adult SIckle Cell Center
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago - Dept of Pediatrics
state: Illinois
city: Shreveport
country: United States
facility: LSU Health Sciences Center - Feist Weiller Cancer Center
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill - Comprehensive Sickle Cell Program
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Dallas
country: United States
facility: Univerisity of Texas Southwestern Medical Center at Dallas - Pediatric Hematology Oncology
state: Texas
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: University Health Network Toronto General Hospital
state: Ontario
city: Cairo
country: Egypt
facility: Abu El Reesh Pediatric University Hospital
city: Mona
country: Jamaica
facility: University of the West Indies - Sickle Cell Unit
state: Kingston
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Rafik Hariri University Hospital
city: Hazmieh
country: Lebanon
facility: Chronic Care Center
Study officials:
affiliation: HemaQuest Pharmaceuticals Inc.
name: Richard Ghalie, MD, MBA
role: STUDY_DIRECTOR
References:
citation: 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.