A Study of HQK-1001 in Patients With Sickle Cell Disease

NCT01322269 | Completed Phase 2 DMC

• 1 other identifier: HQP 1001-SCD-006
• Study Type: interventional
• Target: 52
• Locations: 5 countries
• Sites: 16

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of three dose levels of HQK-1001 administered once daily for 26 weeks in subjects with sickle cell disease.

Conditions

Sickle Cell Disease; Sickle Cell Anemia; Sickle Cell Disorders; Hemoglobin S Disease; Sickling Disorder Due to Hemoglobin S

Outcome Measures

Primary Outcomes (1)

• Safety

  Physical exams, vital signs, clinical laboratory safety assessments, ECG and adverse event monitoring.

  Day 1 through Week 30

Secondary Outcomes (2)

• Fetal hemoglobin levels

  Day 1 and Weeks 4, 8, 12, 16, 20, 25, 26 and 30

• Incidence of sickle cell crisis events

  Day 1 through Week 30

Study Arms (3)

HQK-1001 (30 mg/kg)

EXPERIMENTAL

Drug: HQK-1001

HQK-1001 (40 mg/kg)

EXPERIMENTAL

Drug: HQK-1001

HQK-1001 (50 mg/kg)

EXPERIMENTAL

Drug: HQK-1001

Interventions

HQK-1001 DRUG

HQK-1001 tablets, once daily for daily 26 weeks

HQK-1001 (30 mg/kg); HQK-1001 (40 mg/kg); HQK-1001 (50 mg/kg)

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Established diagnosis of SCD
• Males and females between 12 and 60 years of age, inclusive
• At least 3 episodes of a SCD-related crisis or complication in the 3 years prior to screening OR 1 episode of acute chest syndrome in the 5 years prior to screening
• If receiving hydroxyurea, must be receiving a stable dose for at least 6 months prior to screening
• If hydroxyurea treatment has been discontinued, at least 3 months have elapsed since last dose
• If transfusion in the 4 months prior to screening, then HbA level \< 20% at screening
• Average of the initial two HbF levels ≥ 2.0 % within ≤ 7 days prior to the initial dose of HQK-1001. The two must be obtained ≥ 24 hours apart
• Ability to swallow tablets
• Able and willing to give informed consent and assent (if applicable)
• If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 7 days of first dose of HQK-1001
• If a subject is a WCBP, she must agree to use an effective form of contraception within 7 days of the initial dose of HQK-1001 and for one month after HQK-1001 discontinuation
• Sexually active male subjects (with WCBP partners) must agree to use latex condoms or ensure that their partner(s) use an effective form of contraception
• In the view of the Investigator, subject is able and willing to comply with necessary study procedures

You may not qualify if:

• More than 4 hospitalizations for acute sickle cell related events in the previous 12 months prior to screening
• Pulmonary hypertension requiring oxygen therapy
• QTc \> 450 msec (male) or 470 msec (female) on screening ECG (QT corrected by Fridericia's formula)
• Assigned to a regular transfusion program
• Use of erythropoiesis stimulating agents within 90 days of screening
• ALT \> 3x upper limit of normal (ULN)
• Serum creatinine \> 1.2 mg/dL
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• An acute vaso-occlusive event within 3 weeks prior to screening
• Creatine phosphokinase (CK) \> 20% above the ULN
• 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
• 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 screening

Sponsors & Collaborators

• HemaQuest Pharmaceuticals Inc.: lead

Study Sites (16)

Children's Hospital and Research Center - Oakland

Oakland, California, 94609, United States

Location

University of Miami Miller School of Medicine - Dept of Pediatrics

Miami, Florida, 33101, United States

Location

Georgia Health Sciences University - Adult SIckle Cell Center

Augusta, Georgia, 30912, United States

Location

University of Illinois at Chicago - Dept of Pediatrics

Chicago, Illinois, 60612, United States

Location

LSU Health Sciences Center - Feist Weiller Cancer Center

Shreveport, Louisiana, 71103, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of North Carolina at Chapel Hill - Comprehensive Sickle Cell Program

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Univerisity of Texas Southwestern Medical Center at Dallas - Pediatric Hematology Oncology

Dallas, Texas, 75390-9063, United States

Location

The Hospital for Sick Children

Toronto, Ontario, MSG 1X8, Canada

Location

University Health Network Toronto General Hospital

Toronto, Ontario, MSG 2C4, Canada

Location

Abu El Reesh Pediatric University Hospital

Cairo, Egypt

Location

University of the West Indies - Sickle Cell Unit

Mona, Kingston, Jamaica

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Rafik Hariri University Hospital

Beirut, Lebanon

Location

Chronic Care Center

Hazmiyeh, Lebanon

Location

Related Publications (1)

• Kutlar A, Reid ME, Inati A, Taher AT, Abboud MR, El-Beshlawy A, Buchanan GR, Smith H, Ataga KI, Perrine SP, Ghalie RG. A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Am J Hematol. 2013 Nov;88(11):E255-60. doi: 10.1002/ajh.23533. Epub 2013 Oct 3.

  PMID: 23828223 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

2,2-dimethylbutyric acid

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Richard Ghalie, MD, MBA

  HemaQuest Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2011
• First Posted: March 24, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2012
• Last Updated: June 19, 2013

Record last verified: 2013-06

Locations

CA (2); LE (3); US (9); EG (1); JA (1)