Sickle Cell Disease MedDRA version: 18.0 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850
Conditions
Interventions
Product Name: 5-hydroxymethyl 2 furfural
Product Code: Aes-103
Pharmaceutical Form: Oral solution
INN or Proposed INN: INN Not yet proposed
Current Sponsor code: Aes-103
Concentration unit: mg/ml mill
Sponsors
AesRx
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be male or female, aged 18-60 years old, inclusive 2. Have SCD (hemoglobin SS or S-beta-zero) without hospitalization for any reason in the 14 days before enrollment. Subjects are allowed concomitant usage of HU and other scheduled prescription drugs if the dosage is stable for the 2 months before screening and is at a dosage that does not exceed the product’s labeling. These scheduled prescription medications will be continued during the study. All other medications administered on an as-needed basis, including over-the-counter medications used according to the product labeling, will be permitted except for disulfiram, dextromethorphan, or dextrorphan. Medications for pain management will be allowed as needed. 3. Have normal organ function as defined below: • Direct bilirubin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Have been hospitalized in the 14 days before enrollment, for any reason 2. 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, as judged by the investigator in agreement with the sponsor or medical monitor, 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) 3. Have a history of development of abnormal liver function test (LFT) values in association with administration of xenobiotic provided the causality relationship of the xenobiotic to the LFT abnormality is judged to be at least probably related. 4. Be considered not suitable for participation in this study for any reason, as judged by the investigator 5. Have taken any other investigational drug within 30 days before the screening visit 6. Consumed more than 21 alcohol units per week in the last month or more than 3 units per day in the last week 7. Have received disulfiram or 4-methoxypyrazole within 30 days before dosing (may affect PK results due to assay interference) 8. Have received dextromethorphan or dextrorphan within 7 days before dosing 9. Have taken herbal preparations in the 2 weeks before dosing 10. Have positive result for urine drug test (cocaine, opiates [except prescribed], amphetamines, methamphetamines, benzodiazepines [except prescribed]) at screening visit (A positive test for THC will not be an exclusion)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and pharmacokinetic (PK) profile of four times daily (q.i.d.) dosing of 1000 mg of Aes-103 in Cohort A and up to four additional dosing regimens (to be determined) in Cohort B given for up to 28 days in adult subjects with stable sickle cell disease (SCD) compared with subjects receiving placebo;Secondary Objective: To obtain exploratory evidence of pharmacodynamic (PD) and clinical efficacy endpoint changes from baseline in Aes-103-treated subjects compared with those receiving placebo with respect to the magnitude of effect, time course of effect, and relationship to plasma and red blood cell (RBC) concentrations of Aes-103.;Primary end point(s): The primary safety endpoints will be assessed by the following: •Frequency and severity of AEs, including sickle cell-specific symptoms, such as development of new skin ulcers, hospitalization or ambulatory acute care intravenous analgesics visit for pain episodes, acute chest syndrome, priapism, or stroke. •Changes in other SCD-related symptoms •Changes in vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations. The primary PK endpoints are as follows: •Plasma AUC, Cmax, Tmax, and t1/2 of Aes-103 and its metabolite, HMFA •RBC hemolysate AUC0-8h, Cmax, Tmax, and t1/2 of Aes-103 •Percentage of hemoglobin bound to Aes-103 ;Timepoint(s) of evaluation of this end point: The following safety parameters will be assessed at screening, between 1 and 3 hours before the first dose of lead-in placebo on Day –14, on Days -1, 1, and 4 during the inpatient period, and at each outpatient visit throughout the study unless otherwise specified: • AEs, including sickle cell-specific symptoms (recorded as signs and symptoms before first dose of single-blind placebo on Day –14 and continuously throughout the study thereafter) • Vital signs at 1 to 3 hours after the morning dose and between 9 pm and 10 pm on all inpatient days (also recorded on Day –1 and | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary PD and efficacy endpoints will be change from baseline for each of the two dosing regimens compared to placebo for the following: •Resting oxygen saturation as measured by oximetry (SpO2) •Oxygen binding p50 value •Plasma erythropoietin (EPO) levels •Hematocrit • LDH total levels, anemia/hemoglobin count, reticulocyte percent, and direct bilirubin • LDH isozyme (LDH1, LDH2, LDH3, LDH4, and LDH5) levels • C reactive protein levels • Serum ferritin levels • NT-proBNP levels • Body weight • Exercise tolerance (6MWT and CPET) • Patient Global Impression of Change • Pain levels and analgesic use • Reduction in sickle cell-specific complications;Timepoint(s) of evaluation of this end point: PD and efficacy samples and measurements will be taken between 1 and 3 hours before the first dose and 1 to 3 hours after the first dose of study medication on Day 1 of the double-blind, inpatient period, 1 to 3 hours after the morning dose on Day 7, 1 to 3 hours after the morning dose on Day 28 (or the last day of dosing during the double-blind, outpatient period, if earlier) and on Day 49 (or the last day of the post-dose observation period, if earlier). The following will be • Whole blood will be drawn for p50/p20 assays between 8 pm and 10 pm on the evening before the first dose (Day –1) and between 8 am and 10 am on Days 1, 4 of the inpatient period (Visit 3) and on Day 7 (Visit 4). Please refer to protocol pages x and xi for remaining text. | — |
Countries
United Kingdom
Contacts
Public ContactWarren Stern
AesRx
Outcome results
None listed