Evaluation of Different Dose Regimens of Aes-103 Given for 28 Days to Subjects With Stable Sickle Cell Disease

This study is currently recruiting participants.
Verified November 2013 by AesRx, LLC
Sponsor:
Information provided by (Responsible Party):
AesRx, LLC
ClinicalTrials.gov Identifier:
NCT01987908
First received: October 29, 2013
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Sickle Cell Disease
Drug: Aes-103
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Exploratory, Placebo-Controlled, Multicenter, Double-Blind Evaluation of the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Two Dose Regimens of Aes-103 Given for 28 Days to Subjects With Stable Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by AesRx, LLC:

Primary Outcome Measures:
  • Frequency of adverse events [ Time Frame: Monitored throughout the study, beginning from the time the subject is administered the first dose at the start of the outpatient run-in through the final clinic visit, for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    Measurement of spontaneously reported adverse events prior to the start of study drug, during dosing and after dosing ends. Related safety measures include vital signs, clinical laboratory tests, and physical exams


Secondary Outcome Measures:
  • Hemoglobin [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood

  • Measurement of drug levels in blood [ Time Frame: On Days 1 and 7 of the inpatient dosing period and on the last day of the outpatient dosing period for an approximate total of 7 weeks ] [ Designated as safety issue: No ]
    Determination in plasma and red blood cells of Aes-103 and its metabolite, HMFA; determination of percentage of hemoglobin bound to Aes-103

  • Lactate dehydrogenase (LDH) [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A clinical laboratory endpoint that reflects the amount of destruction of red blood cells

  • SpO2% [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A measure of the amount of oxygen in the blood

  • p50 [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A measure of the ability of hemoglobin to bind oxygen

  • Pain ratings [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A clinical measure of the effects of sickle cell disease on the functioning of the patient using a pain scale, pain inventory, and record of analgesic use

  • Exercise Tolerance [ Time Frame: Measured prior to, during and after the end of dosing for a total of approximately 9 weeks ] [ Designated as safety issue: Yes ]
    A clinical measure of the effects of sickle cell disease on the physical functioning of the patient using a 6 minute walk test


Estimated Enrollment: 50
Study Start Date: October 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A (Drug)
Subjects randomized 3:1 to receive 4 times daily dosing of 1,000 mg of Aes 103 or placebo for 28 days
Drug: Aes-103
The active ingredient in Aes-103 is 5-hydroxymethyl furfural (5-HMF). Aes-103 and matching placebo are administered in a liquid oral formulation.
Placebo Comparator: Cohort A (Placebo)
Subjects randomized 3:1 to receive 4 times daily dosing of 1,000 mg of Aes 103 or placebo
Other: Placebo
Experimental: Cohort B (Drug)
In this adaptive design, the dose frequency and the total amount given per day to Cohort B will be adjusted depending on the tolerability, clinical pharmacology and clinical endpoint results of Cohort A
Drug: Aes-103
The active ingredient in Aes-103 is 5-hydroxymethyl furfural (5-HMF). Aes-103 and matching placebo are administered in a liquid oral formulation.
Placebo Comparator: Cohort B (Placebo)
The dosing regiment of placebo will match that of the Aes-103 treatment in Cohort B.
Other: Placebo

Detailed Description:

This study will evaluate evaluate in subjects with stable SCD the safety, pharmacokinetic profile, clinical pharmacology actions and clinical activities of two dosing regimens of Aes-103 (1000 mg four times daily in Cohort A and a higher or lower dose given once daily or up to four times daily in Cohort B) given for up to 28 days in adult subjects with stable SCD compared with subjects receiving placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01987908

Locations
United Kingdom
Quintiles Guy's Hospital Drug Research Unit, 6 Newcomen Street Recruiting
London, United Kingdom, SE1 1YR
Contact: Timothy Mant, MBBS    44 (0)20-7910-7809    Tim.Mant@Quintiles.com   
Principal Investigator: Timothy Mant, MBBS         
Sponsors and Collaborators
AesRx, LLC
  More Information

No publications provided

Responsible Party: AesRx, LLC
ClinicalTrials.gov Identifier: NCT01987908     History of Changes
Other Study ID Numbers: Aes-103-003
Study First Received: October 29, 2013
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AesRx, LLC:
Aes-103
5-HMF
Sickle cell disease
Anemia
Hemoglobin
Pain
Analgesic use
6 minute walk test
Pharmacokinetics
SpO2
Biomarkers

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 17, 2014