Conditions: Sickle Cell Disease
Keywords: Pain Biomarkers 6 minute walk test 5-HMF Pharmacokinetics Analgesic use Sickle cell disease Aes-103 SpO2 Anemia Hemoglobin
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 35
Healthy volunteers: no

Brief 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.

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.

Arms:
arm 1: Subjects randomized 3:1 to receive 4 times daily dosing of 1,000 mg of Aes 103 or placebo for 28 days arm 2: Subjects randomized 3:1 to receive 4 times daily dosing of 1,000 mg of Aes 103 or placebo arm 3: 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. Study terminated prior to completion of Cohort A due to unblinding between study product and placebo groups for participant, site and Sponsor. The study was stopped before initiation of Cohort B. arm 4: The dosing regiment of placebo will match that of the Aes-103 treatment in Cohort B. Study terminated prior to completion of Cohort A due to unblinding between study product and placebo groups for participant, site and Sponsor. The study was stopped before initiation of Cohort B.

Interventions: intervention 1: Aes-103 intervention 2: Placebo
Intervention descriptions: intervention 1: The active ingredient in Aes-103 is 5-hydroxymethyl furfural (5-HMF). Aes-103 and matching placebo are administered in a liquid oral formulation. intervention 2: None

Protocol document: