Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 Administered Daily in Patients With Sickle Cell Disease

A Randomized, Blinded, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 in Subjects With Sickle Cell Disease

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: HQK-1001; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Jamaica
  • Mona
    • Kingston, Mona, Jamaica, 7
      • University of the West Indies, mona
• United States
  • Alabama
    • Madison, Alabama, United States, 35758
      • Trialogic Research
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center at Oakland
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Century Clinical Research, Inc.
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Comprehensive Sickle Cell Program
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Cancer Center and Hematology Service

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Matching placebo capsule. Administered orally once a day on dosing days.
EXPERIMENTAL: Active	Drug: HQK-1001; HQK-1001 capsules. 10 mg/kg, 20 mg/kg or 30 mg/kg administered once a day on dosing days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety as assessed by (1) adverse events (2) laboratory values (3) vital signs, and (4) physical exam.	126 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics assessed by plasma drug concentration levels.	Days 0, 6, 69 and 97 post first dose
Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin.	Every 2 weeks through Day 126 post first dose

Collaborators and Investigators

• Sponsor: HemaQuest Pharmaceuticals Inc.
• Investigators: Study Director: Susan Perrine, M.D., HemaQuest Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: February 11, 2009
• First Submitted That Met QC Criteria: February 11, 2009
• First Posted (ESTIMATE): February 12, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 1, 2011
• Last Update Submitted That Met QC Criteria: July 28, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: HQP 2008-004