Evaluation of Different Dose Regimens of Aes-103 Given for 28 Days to Subjects With Stable Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Aes-103; Placebo
Intervention description: The active ingredient in Aes-103 is 5-hydroxymethyl furfural (5-HMF). Aes-103 and matching placebo are administered in a liquid oral formulation.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Pain; Biomarkers; 6 minute walk test; 5-HMF; Pharmacokinetics; Analgesic use; Sickle cell disease; Aes-103; SpO2; Anemia; Hemoglobin

Summary:

      Sickle cell disease (SCD) is a genetic blood disorder characterized by the presence of
      sickle-shaped red blood cells. In the U.S. and the U.K. this occurs primarily in persons of
      African origin. There is only one drug (hydroxyurea) approved to manage SCD, but it is not
      fully efficacious and can produce medically significant side effects. Aes-103 is being
      evaluated as a novel agent for the long term management of SCD. By directly reducing the
      sickling process, Aes-103 has a different mechanism of action than hydoxyurea. The active
      ingredient in Aes-103 is 5-hydroxymethyl furfural, a naturally occurring small molecule that
      is chemically related to glucose.

      This study will evaluate the safety and pharmacokinetic profile of two dosing regimens of
      Aes-103 for up to 28 days in up to 50 adult subjects with stable SCD compared with subjects
      receiving placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged 18-60 years old, inclusive

          -  Diagnosis of SCD (hemoglobin SS) without hospitalization for pain crises or any other
             reason in the 14 days before enrollment

          -  Have normal organ function as defined by direct bilirubin <1.1 mg/dL (19 μmol/L),
             alanine transaminase (serum glutamic pyruvic transaminase) ≤120 IU/L, and Creatinine
             ≤1.3 mg/dL (115 μmol/L)

          -  Have at least one of the following baseline values: hemoglobin level of <10 g/dL,
             numerical pain rating scale (NPRS) score of ≥ 4, or 6-minute walk distance (6MWD) of
             <500 m

          -  If female, be nonpregnant and nonbreastfeeding and be surgically sterile or using an
             acceptable method of contraception throughout the study and for 3 months after the
             last dose of study medication

          -  Have completed an outpatient screening visit consisting of medical history, physical
             examination, 12-lead electrocardiogram (ECG), vital signs, hematology and chemistry
             tests, urinalysis, urine drug screen, urine or serum pregnancy test (females),
             hemoglobin electrophoresis, hepatitis B and C screening, and HIV serology

          -  Be able to understand and have provided written informed consent including signature
             on an informed consent form approved by an institutional review board or independent
             ethics committee

          -  Have provided written authorization for use and disclosure of protected health
             information

          -  Agree to abide by the study schedule and to return for the required assessments

        Exclusion Criteria:

          -  Have been hospitalized in the 14 days before enrollment, for any reason

          -  Have evidence of clinically significant cardiovascular, respiratory, renal, hepatic,
             pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other
             disease that may interfere with the objectives of the study or the safety of the
             subject, or have been hospitalized in the past 6 months as a result of these
             conditions (for SCD-related morbidity, a minimum of 14 days from the last
             hospitalization is required)