A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease

Sponsor
EpiDestiny, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04055818
Collaborator
National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
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Study Details

Study Description

Brief Summary

A randomized control trial in 20 subjects with sickle cell disease comparing oral THU-decitabine to nicotinamide and in combination (THU, decitabine and nicotinamide).

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

A randomized control trial comparing oral THU-decitabine to nicotinamide (1:1 randomization), and then comparing the effects of the combination of nicotinamide with THU-decitabine vs either treatment alone. Treatment with each agent alone is for 12 weeks followed by the combination for a further 12 weeks. Patients have the option to enter an extension phase of combination treatment for an additional 24 weeks (total of 48 weeks)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
1:1 Randomization1:1 Randomization
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease
Actual Study Start Date :
Jan 24, 2020
Anticipated Primary Completion Date :
Feb 5, 2023
Anticipated Study Completion Date :
Mar 3, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nicotinamide

Oral Nicotinamide 1000 mg twice daily

Drug: Nicotinamide
Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
Other Names:
  • Decitabine
  • Tetrahydrouridine
  • Experimental: THU Decitabine

    Oral 250 mg THU and 5 mg decitabine Once per week

    Drug: Nicotinamide
    Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
    Other Names:
  • Decitabine
  • Tetrahydrouridine
  • Outcome Measures

    Primary Outcome Measures

    1. Blood Hemoglobin [12 weeks]

      Measure hemoglobin function

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age 18 years or older.

    • Written informed consent provided by the subject before study entry.

    • Confirmed sickle cell disease (SCD) as determined by hemoglobin electrophoresis or liquid chromatography.

    • Subject is in his/her steady state and not having any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).

    • Weight at least 40kg

    • Regular compliance with comprehensive care and previous therapy.

    • Symptomatic SCD is defined as having one of following, despite at least 6 months of hydroxyurea therapy, or refuse to take hydroxyurea for personal reasons: fetal hemoglobin <0.5 g/dL, or 3 or more pain episodes per year requiring parenteral narcotics, or 1 or more acute chest syndrome episodes, or Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.

    Exclusion Criteria:
    • Inability to give informed consent.

    • Experienced severe sepsis or septic shock within the previous 12 weeks.

    • Last HU dose was ingested within the previous 4 weeks.

    • Currently pregnant or breast-feeding.

    • Alanine Aminotransferase (ALT) ≥ 3 times the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl.

    • Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.

    • Platelet count >800 x 109/L.

    • Absolute neutrophil count <1.5 x 109/L.

    • Female of active childbearing potential who is unwilling to use at least one of the two following forms of birth control: (i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of decitabine OR (ii) intrauterine device (IUD).

    • Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of THU and decitabine. This requirement applies also to males who have had a successful vasectomy.

    • Altered mental status or recurrent seizures requiring anti-seizure medications.

    • Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.

    • Concurrent diagnosis of malignancy including known Myelodysplastic syndrome, leukemia, or an abnormal karyotype.

    • New York Heart Association (NYHA) class III/IV status.

    • Eastern Co-operative Oncology Group (ECOG) performance status ≥3.

    • Participant is on chronic transfusion therapy

    • Known history of illicit drug or alcohol abuse within the past 12 months.

    • Other experimental or investigational drug therapy in the past 28 days.

    • Taking l-glutamine within the last 28 days

    • Being positive for HIV infection

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Illinois at Chicago College of Medicine Chicago Illinois United States 60612

    Sponsors and Collaborators

    • EpiDestiny, Inc.
    • National Institutes of Health (NIH)
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Robert Molokie, University of Illinois at Chicago College of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    EpiDestiny, Inc.
    ClinicalTrials.gov Identifier:
    NCT04055818
    Other Study ID Numbers:
    • 2019-0631
    • P01HL146372
    • R44HL135896
    First Posted:
    Aug 14, 2019
    Last Update Posted:
    Mar 22, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 22, 2022