Clinical trial NCT00842088: Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 Administered Daily in Patients With Sickle Cell Disease
Official title: A Randomized, Blinded, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 in Subjects With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Lead sponsor: HemaQuest Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2009-02-12
Enrollment: 24
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 assess the safety and tolerability of HQK-1001 administered for a total of 12 weeks (with one dosing break) in subjects with sickle cell disease.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of SCD or sickle beta thalassemia (excluding Hemoglobin C)
* Between 12 and 60 years of age, inclusive
* At least one episode of a SCD-related crisis or complication (e.g., vaso-occlusive crisis, acute chest syndrome, priapism) per year for an average of 3 years or one episode of acute chest syndrome over the prior 5 years
* Screening (untransfused) HbF level \>/= 2% as analyzed by a central laboratory
* If receiving hydroxyurea therapy, must be receiving a stable dose for at least 6 months
* Able and willing to give informed consent
* If female, must have a negative serum pregnancy test within 7 days of dosing
* If female, must not be of childbearing potential defined as post-menopausal by at least 2 years or surgically sterile, or must agree to use a medically accepted form of contraception throughout the study
* If the sexual partner of a male subject is a WCBP, she must agree to use a medically accepted form of birth control for themselves or their partner throughout the study
* In the view of the Investigator, able to comply with necessary study procedures

Exclusion Criteria:

* Red blood cell (RBC) transfusion within 3 months prior to beginning study medication
* Participation in a regular blood transfusion program
* More than 4 hospitalizations for acute sickle cell-related events in the previous 12 months
* An acute vaso-occlusive event within 3 weeks prior to receiving first dose of study medication
* Pulmonary hypertension requiring oxygen
* QTc \> 450 msec on screening
* Alanine transaminase (ALT) \> 3X upper limit of normal (ULN)
* Creatinine phosphokinase (CPK) \> 20% above the ULN
* Serum creatinine \>1.2 mg/dL
* An acute illness (e.g., febrile, gastrointestinal \[GI\], respiratory) within 72 hours prior to receiving first dose of study medication
* 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 administration of study medication
* 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 as assessed by (1) adverse events (2) laboratory values (3) vital signs, and (4) physical exam.
timeFrame: 126 days
Secondary outcomes:
measure: Pharmacokinetics assessed by plasma drug concentration levels.
timeFrame: Days 0, 6, 69 and 97 post first dose
measure: Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin.
timeFrame: Every 2 weeks through Day 126 post first dose
Other outcomes:
Locations:
city: Madison
country: United States
facility: Trialogic Research
state: Alabama
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Daytona Beach
country: United States
facility: Century Clinical Research, Inc.
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Chapel Hill
country: United States
facility: UNC Comprehensive Sickle Cell Program
state: North Carolina
city: Houston
country: United States
facility: Texas Children's Cancer Center and Hematology Service
state: Texas
city: Kingston
country: Jamaica
facility: University of the West Indies, Mona
state: Mona
Study officials:
affiliation: HemaQuest Pharmaceuticals
name: Susan Perrine, M.D.
role: STUDY_DIRECTOR
References:
citation: Kutlar A, Ataga K, Reid M, Vichinsky EP, Neumayr L, Blair-Britt L, Labotka R, Glass J, Keefer JR, Wargin WA, Berenson R, Perrine SP. A phase 1/2 trial of HQK-1001, an oral fetal globin inducer, in sickle cell disease. Am J Hematol. 2012 Nov;87(11):1017-21. doi: 10.1002/ajh.23306. Epub 2012 Aug 7.