Effects of HQK-1001 in Patients With Sickle Cell Disease

NCT01601340 | Terminated Phase 2 DMC

• 1 other identifier: HQP 1001-SCD-007
• Study Type: interventional
• Target: 77
• Locations: 5 countries
• Sites: 18

Brief Summary

The purpose of this study is to evaluate the effects of HQK-1001 on Hb F 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)

• Change from baseline in % fetal hemoglobin

  Day 1 through Week 48

Secondary Outcomes (5)

• Incidence and number of SCD pain crises and SCD-related complications

  Day 1 through Week 52

• Subject reported daily pain scale scores and analgesic use

  7 consecutive days following clinic visits at Day 1, and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

• Change in FACIT Fatigue Scale results

  Day 1 and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

• Safety measured by the frequency and severity of adverse events, and changes from baseline in vital signs, electrocardiogram (ECG) monitoring, and laboratory assessments

  Day 1 through Week 52

• HQK-1001 pharmacokinetic parameters

  1 hour prior to, and 2 hours following morning dose on Weeks 12, 24 and 48

Study Arms (2)

HQK-1001

ACTIVE COMPARATOR

Drug: HQK-1001

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

HQK-1001 DRUG

HQK-1001 tablets, twice daily for 48 weeks

HQK-1001

Placebo DRUG

Placebo tablets, twice daily for 48 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• HemaQuest Pharmaceuticals Inc.: lead

Study Sites (18)

University of South Alabama

Mobile, Alabama, 36617-2238, United States

Location

Children's Hospital and Research Center - Oakland

Oakland, California, 94609, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Howard University Hospital

Washington D.C., District of Columbia, 20060, United States

Location

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

The Children's Hospital at Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Virginia Commonwealth Univeristy - Center on Health Disparities

Richmond, Virginia, 23298, United States

Location

University Health Network Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

Abu El Reesh Pediatric University Hospital

Cairo, Egypt

Location

Ain Sham University Hospital

Cairo, Egypt

Location

University of the West Indies

Mona, Kingston 7, Jamaica

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Chronic Care Center

Beirut, Lebanon

Location

Rafik Hariri University Hospital

Beirut, Lebanon

Location

Related Publications (1)

• 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.

  PMID: 24677033 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2012
• First Posted: May 18, 2012
• Study Start: July 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

JA (1); EG (2); CA (1); US (11); LE (3)