Effects of HQK-1001 in Patients With Sickle Cell Disease
Primary Purpose
Sickle Cell Disease, Sickle Cell Anemia, Sickle Cell Disorders
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
HQK-1001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for 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
Sites / Locations
- University of South Alabama
- Children's Hospital and Research Center - Oakland
- Children's National Hospital
- Howard University Hospital
- Georgia Health Sciences University
- University of Illinois at Chicago
- Tufts Medical Center
- The Children's Hospital at Montefiore Medical Center
- New York Methodist Hospital
- University of North Carolina at Chapel Hill
- Virginia Commonwealth Univeristy - Center on Health Disparities
- University Health Network Toronto General Hospital
- Abu El Reesh Pediatric University Hospital
- Ain Sham University Hospital
- University of the West Indies
- American University of Beirut Medical Center
- Chronic Care Center
- Rafik Hariri University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
HQK-1001
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline in % fetal hemoglobin
Secondary Outcome Measures
Incidence and number of SCD pain crises and SCD-related complications
Subject reported daily pain scale scores and analgesic use
Change in FACIT Fatigue Scale results
Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments
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.
Full Information
NCT ID
NCT01601340
First Posted
May 12, 2012
Last Updated
March 17, 2015
Sponsor
HemaQuest Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01601340
Brief Title
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
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Study Start Date
July 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HemaQuest Pharmaceuticals Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effects of HQK-1001 on Hb F in subjects with sickle cell disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Sickle Cell Anemia, Sickle Cell Disorders, Hemoglobin S Disease, Sickling Disorder Due to Hemoglobin S
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HQK-1001
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
HQK-1001
Intervention Description
HQK-1001 tablets, twice daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets, twice daily for 48 weeks
Primary Outcome Measure Information:
Title
Change from baseline in % fetal hemoglobin
Time Frame
Day 1 through Week 48
Secondary Outcome Measure Information:
Title
Incidence and number of SCD pain crises and SCD-related complications
Time Frame
Day 1 through Week 52
Title
Subject reported daily pain scale scores and analgesic use
Time Frame
7 consecutive days following clinic visits at Day 1, and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Title
Change in FACIT Fatigue Scale results
Time Frame
Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Title
Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments
Time Frame
Day 1 through Week 52
Title
HQK-1001 pharmacokinetic parameters
Description
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.
Time Frame
1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Ghalie, MD, MBA
Organizational Affiliation
HemaQuest Pharmaceuticals Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of South Alabama
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36617-2238
Country
United States
Facility Name
Children's Hospital and Research Center - Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's National Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Howard University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20060
Country
United States
Facility Name
Georgia Health Sciences University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
The Children's Hospital at Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Virginia Commonwealth Univeristy - Center on Health Disparities
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University Health Network Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2C4
Country
Canada
Facility Name
Abu El Reesh Pediatric University Hospital
City
Cairo
Country
Egypt
Facility Name
Ain Sham University Hospital
City
Cairo
Country
Egypt
Facility Name
University of the West Indies
City
Mona, Kingston 7
Country
Jamaica
Facility Name
American University of Beirut Medical Center
City
Beirut
Country
Lebanon
Facility Name
Chronic Care Center
City
Beirut
Country
Lebanon
Facility Name
Rafik Hariri University Hospital
City
Beirut
Country
Lebanon
12. IPD Sharing Statement
Citations:
PubMed Identifier
24677033
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.
Results Reference
derived
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Effects of HQK-1001 in Patients With Sickle Cell Disease
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