Clinical trial NCT01601340: Effects of HQK-1001 in Patients With Sickle Cell Disease
Official title: A Randomized, Placebo-controlled, Phase 2 Study of HQK-1001 in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
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: 2012-05-18
Enrollment: 77
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 effects of HQK-1001 on Hb F in subjects with sickle cell disease.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in % fetal hemoglobin
timeFrame: Day 1 through Week 48
Secondary outcomes:
measure: Incidence and number of SCD pain crises and SCD-related complications
timeFrame: Day 1 through Week 52
measure: Subject reported daily pain scale scores and analgesic use
timeFrame: 7 consecutive days following clinic visits at Day 1, and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Change in FACIT Fatigue Scale results
timeFrame: Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments
timeFrame: Day 1 through Week 52
measure: HQK-1001 pharmacokinetic parameters
timeFrame: 1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Oakland
country: United States
facility: Children's Hospital and Research Center - Oakland
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth Univeristy - Center on Health Disparities
state: Virginia
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: Cairo
country: Egypt
facility: Ain Sham University Hospital
city: Mona, Kingston 7
country: Jamaica
facility: University of the West Indies
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Chronic Care Center
city: Beirut
country: Lebanon
facility: Rafik Hariri University Hospital
Study officials:
affiliation: HemaQuest Pharmaceuticals Inc.
name: Richard Ghalie, MD, MBA
role: STUDY_DIRECTOR
References:
citation: 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.