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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00842088
• Other study ID #: HQP 2008-004
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 11, 2009
• Last updated: July 28, 2011
• Start date: March 2009

Study information

• Verified date: July 2011
• Source: HemaQuest Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Placebo
Matching placebo capsule. Administered orally once a day on dosing days.
• HQK-1001
HQK-1001 capsules. 10 mg/kg, 20 mg/kg or 30 mg/kg administered once a day on dosing days.

Locations

Country	Name	City	State
Jamaica	University of the West Indies, Mona	Kingston	Mona
United States	Medical College of Georgia	Augusta	Georgia
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	UNC Comprehensive Sickle Cell Program	Chapel Hill	North Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Century Clinical Research, Inc.	Daytona Beach	Florida
United States	Texas Children's Cancer Center and Hematology Service	Houston	Texas
United States	Trialogic Research	Madison	Alabama
United States	Children's Hospital and Research Center at Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
HemaQuest Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Jamaica, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as assessed by (1) adverse events (2) laboratory values (3) vital signs, and (4) physical exam.		126 days	Yes
Secondary	Pharmacokinetics assessed by plasma drug concentration levels.		Days 0, 6, 69 and 97 post first dose	No
Secondary	Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin.		Every 2 weeks through Day 126 post first dose	No