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

Sponsor

Baxalta now part of Shire (Industry)

Overall Status

Terminated

CT.gov ID

NCT01987908

Collaborator

(none)

Enrollment

Location

Arms

15.4

Actual Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Actual Study Start Date :

Dec 3, 2013

Actual Primary Completion Date :

Mar 16, 2015

Actual Study Completion Date :

Mar 16, 2015

Arms and Interventions

Arm	Intervention/Treatment
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. 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.	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. 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.	Other: Placebo

Outcome Measures

Primary Outcome Measures

Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period [Double-blind treatment period of 28 days (Day 1 to Day 28)]
Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period [Placebo lead-in period of 14 days (Day -14 to Day -1)]
Number of participants with adverse events (AEs) reported during the placebo lead-in period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period [Post-treatment observation period of 21 days (Day 29 to Day 49)]
Number of participants with adverse events (AEs) reported during the post-treatment observation period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Number of Participants With Sickle-Cell Disease-related Symptoms [Placebo lead-in period of 14 days (Day -14 to Day -1), double-blind treatment period of 28 days (Day 1 to Day 28) and post-treatment observation period of 21 days (Day 29 to Day 49)]
Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations [Throughout the study period (approximately 9 weeks)]
Vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations that were deemed clinically significant by the investigator in agreement with the sponsor study director.
PK: - Plasma AUC, Cmax, Tmax, and T1/2 of Aes-103 and Its Metabolite, HMFA - RBC Hemolysate AUC (0-8h), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of Hemoglobin Bound to Aes-103 [PK blood samples were to be taken within 10 minutes before dosing and 0.5, 1, 2, 4, and 6 hours after the first dose of study product on Days 1 and 7 and at the same time points on Day 28 (or early termination)]
Pharmacokinetic endpoints in the study protocol were as follows:- - Plasma Area under curve (AUC), Maximum plasma concentration (Cmax), time at which Cmax observed (Tmax), and terminal half-life (T1/2) of Aes-103 and its metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) - red blood cell (RBC) hemolysate Area under curve between 0 and 8 hours (AUC [0-8h]), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of hemoglobin bound to Aes-103

Secondary Outcome Measures

Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28]
A measure of the amount of oxygen in the blood. Oxygen saturation was determined by pulse oximetry. A pulse oximeter was placed over a nail polish-free finger nail to determine peripheral oxygen saturation (SpO2). Baseline was defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. A mean change from baseline >0 indicates an increase in oxygen saturation, a mean change <0 indicates a decrease in oxygen saturation. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Oxygen Binding p50/p20 Value - Change From Baseline [During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7]
A measure of the ability of hemoglobin to bind oxygen. The p50 is the oxygen level at which 50% of the hemoglobin contains oxygen. The p20 is the oxygen level at which 20% of the hemoglobin contains oxygen. Baseline is defined as the most recent value obtained prior to start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Plasma Erythropoietin (EPO) Levels - Change From Baseline [At baseline and Day 28 during the double-blind treatment period]
Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. EPO can be detected and measured in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Hematocrit Levels - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28]
Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Lactate Dehydrogenase (LDH) Levels - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28]
LDH levels were measured as a biomarker for intravascular hemolysis. The results are based on the LDH Total measurement. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Hemoglobin Levels - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28]
A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Reticulocyte Percent- Change From Baseline [At baseline, Day 1 and Day 7 during the double-blind treatment period]
Category title includes number of participants with available data (n) for participants treated with study product.
Direct Bilirubin - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14, Day 21 and Day 28]
Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
LDH Isoform - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28]
C Reactive Protein Levels - Change From Baseline [At baseline, Day 1 and Day 7 during the double-blind treatment period]
Category title includes number of participants with available data (n) for participants treated with study product.
Serum Ferritin Levels - Change From Baseline [At baseline, Day 1 and Day 7 during the double-blind treatment period]
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline [At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period]
Category title includes number of participants with available data (n) for participants treated with study product.
Body Weight - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28]
A negative change in body weight denotes a weight decrease, a positive change in body weight denotes a weight increase. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline [Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28]
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline [Prior to dosing at baseline and on Day 49 of the post-treatment observation period]
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1.
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) [On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period]
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results.
Exercise Tolerance: Cardiopulmonary Exercise Test [CPET] [On last day of double-blind treatment period (Day 28)]
CPET was optional, based on capacity of participant to complete the test.
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline [At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period]
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. No values available for placebo group for Day 28. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline [At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period]
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period [At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period]
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline was defined as the most recent value obtained on the last day of the double-blind treatment period. Categories contain Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21. and Day 28.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 49.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC [Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments]
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Area under the curve (AUC) was computed using change from baseline (Day 28) in weekly average values at Day 35, Day 42 and Day 49.
Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline [At baseline, Day 7 and Day 28 during the double-blind treatment period]
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline [At baseline, Day 7 and Day 28 during the double-blind treatment period]
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline [At baseline and Day 49 during the post-treatment observation period]
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline [At baseline, Day 7 and Day 28 during the double-blind treatment period]
Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline [At baseline and Day 49 during the post-treatment observation period]
Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Analgesic Use [Throughout the study period (approximately 9 weeks)]
Analgesic use assessed with pain levels by numerical pain rating scale (NPRS) and brief pain inventory (BPI).
Reduction in Sickle Cell-specific Complications [Throughout the study period (approximately 9 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Quintiles Ltd. - Quintiles Drug Research Unit, 6 Newcomen Street	London		United Kingdom	SE1 1YR

Sponsors and Collaborators

Baxalta now part of Shire

Investigators

Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Baxalta now part of Shire

ClinicalTrials.gov Identifier:

NCT01987908

Other Study ID Numbers:

Aes-103-003
321401
2013-001534-18

First Posted:

Nov 20, 2013

Last Update Posted:

May 25, 2021

Last Verified:

May 1, 2021

Keywords provided by Baxalta now part of Shire

Additional relevant MeSH terms:

Anemia, Sickle Cell

Study Results

Participant Flow

Recruitment Details	Enrollment was conducted at one clinical site in the United Kingdom with referrals and/or patient identification from five other clinical sites in the United Kingdom.
Pre-assignment Detail	35 participants were enrolled. 10 failed screen and 2 were randomization failures. 23 started the 2-week, single-blind, placebo lead-in period (to obtain stable baseline values and to screen out participants who did not tolerate placebo or were not compliant with study procedures).

Arm/Group Title	Placebo lead-in Period	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo	After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days during the double-blind treatment period	After placebo lead-in period, participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days during the double-blind treatment period
Period Title: Placebo Lead-in Period
STARTED	23	0	0
COMPLETED	14	0	0
NOT COMPLETED	9	0	0
Period Title: Placebo Lead-in Period
STARTED	0	11	3
COMPLETED	0	10	2
NOT COMPLETED	0	1	1
Period Title: Placebo Lead-in Period
STARTED	0	10	2
COMPLETED	0	7	2
NOT COMPLETED	0	3	0

Baseline Characteristics

Arm/Group Title	Placebo lead-in Period
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Overall Participants	23
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	28 (7)
Sex: Female, Male (Count of Participants)
Female	13 56.5%
Male	10 43.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period
Description	Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time Frame	Double-blind treatment period of 28 days (Day 1 to Day 28)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo	All Treated Participants
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	All participants randomized 3:1 (Aes-103 to placebo) and received 4 times daily dosing of 1,000 mg AEs-103 or 1,000 mg of placebo for 28 days
Measure Participants	11	3	14
Treatment-emergent AEs	9 39.1%	3 NaN	12 NaN
Related AEs	8 34.8%	2 NaN	10 NaN
Serious AEs	0 0%	0 NaN	0 NaN
Severe AEs	0 0%	0 NaN	0 NaN
AEs leading to discontinuation	1 4.3%	1 NaN	2 NaN
AEs leading to death	0 0%	0 NaN	0 NaN
Sickle-cell specific complications	4 17.4%	1 NaN	5 NaN

2. Primary Outcome

Title	Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period
Description	Number of participants with adverse events (AEs) reported during the placebo lead-in period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time Frame	Placebo lead-in period of 14 days (Day -14 to Day -1)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Placebo lead-in Period
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Measure Participants	23
Treatment-emergent AEs	21 91.3%
Related AEs	12 52.2%
Serious AEs	2 8.7%
Severe AEs	2 8.7%
AEs leading to discontinuation	2 8.7%
AEs leading to death	0 0%
Sickle cell-specific complications	2 8.7%

3. Primary Outcome

Title	Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period
Description	Number of participants with adverse events (AEs) reported during the post-treatment observation period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time Frame	Post-treatment observation period of 21 days (Day 29 to Day 49)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period	All Participants in Post-treatment Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no placebo was received	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) or placebo was received
Measure Participants	10	2	12
Treatment-emergent AEs	4 17.4%	0 NaN	4 NaN
Related AEs	2 8.7%	0 NaN	2 NaN
Serious AEs	1 4.3%	0 NaN	1 NaN
Severe AEs	1 4.3%	0 NaN	1 NaN
AEs leading to discontinuation	0 0%	0 NaN	0 NaN
AEs leading to death	0 0%	0 NaN	0 NaN
Sickle cell-specific complications	2 8.7%	0 NaN	2 NaN

4. Primary Outcome

Title	Number of Participants With Sickle-Cell Disease-related Symptoms
Description
Time Frame	Placebo lead-in period of 14 days (Day -14 to Day -1), double-blind treatment period of 28 days (Day 1 to Day 28) and post-treatment observation period of 21 days (Day 29 to Day 49)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Placebo Lead-in Period	Treatment With Study Product	Treatment With Placebo	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no placebo was received
Measure Participants	23	11	3	10	2
Abdominal Pain - Sickle Pain	0 0%	1 NaN	0 NaN	0 NaN	0 NaN
Exacerbation of Sickle Cell (SC) Disease Pain	1 4.3%	1 NaN	0 NaN	1 NaN	0 NaN
SC Disease Related Pain	0 0%	3 NaN	0 NaN	1 NaN	0 NaN
SC Pain	3 13%	3 NaN	1 NaN	1 NaN	0 NaN
Intermittent SC Pain	1 4.3%	0 NaN	0 NaN	0 NaN	0 NaN
SC Crisis	1 4.3%	0 NaN	0 NaN	0 NaN	0 NaN
Vaso-Occlusive Crisis caused by Chest Infection	1 4.3%	0 NaN	0 NaN	0 NaN	0 NaN

5. Primary Outcome

Title	Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations
Description	Vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations that were deemed clinically significant by the investigator in agreement with the sponsor study director.
Time Frame	Throughout the study period (approximately 9 weeks)

Outcome Measure Data

Analysis Population Description
safety analysis dataset

Arm/Group Title	Placebo lead-in Period	Double-blind Treatment Period - Study Product	Double-blind Treatment Period - Placebo	Post-treatment Observation Period
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo (Day -14 to Day -1)	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days (Day 1 to Day 28)	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of placebo for 28 days (Day 1 to Day 28)	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) or placebo was received (Day 29 to Day 49)
Measure Participants	23	11	3	12
Electrocardiogram T Wave Inversion	0	1	0	0
Transaminases Increased	0	0	1	0

6. Primary Outcome

Title	PK: - Plasma AUC, Cmax, Tmax, and T1/2 of Aes-103 and Its Metabolite, HMFA - RBC Hemolysate AUC (0-8h), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of Hemoglobin Bound to Aes-103
Description	Pharmacokinetic endpoints in the study protocol were as follows:- - Plasma Area under curve (AUC), Maximum plasma concentration (Cmax), time at which Cmax observed (Tmax), and terminal half-life (T1/2) of Aes-103 and its metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) - red blood cell (RBC) hemolysate Area under curve between 0 and 8 hours (AUC [0-8h]), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of hemoglobin bound to Aes-103
Time Frame	PK blood samples were to be taken within 10 minutes before dosing and 0.5, 1, 2, 4, and 6 hours after the first dose of study product on Days 1 and 7 and at the same time points on Day 28 (or early termination)

Outcome Measure Data

Analysis Population Description
PK data were not determined as the assay collection method was found to be faulty rendering all samples unevaluable.

Arm/Group Title	Overall Study Arm
Arm/Group Description	Data not collected
Measure Participants	0

7. Secondary Outcome

Title	Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline
Description	A measure of the amount of oxygen in the blood. Oxygen saturation was determined by pulse oximetry. A pulse oximeter was placed over a nail polish-free finger nail to determine peripheral oxygen saturation (SpO2). Baseline was defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. A mean change from baseline >0 indicates an increase in oxygen saturation, a mean change <0 indicates a decrease in oxygen saturation. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 4 (n=9, 3)	0 (2)	4 (5)
Day 7 (n= 9, 3)	0 (2)	-4 (8)
Day 14 (n=8, 2)	0 (2)	8 (10)
Day 28 (n=8, 2)	0 (3)	6 (8)

8. Secondary Outcome

Title	Oxygen Binding p50/p20 Value - Change From Baseline
Description	A measure of the ability of hemoglobin to bind oxygen. The p50 is the oxygen level at which 50% of the hemoglobin contains oxygen. The p20 is the oxygen level at which 20% of the hemoglobin contains oxygen. Baseline is defined as the most recent value obtained prior to start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	0.0 (0.2)	0.0 (0.2)
Day 4 (n=11, 3)	0.0 (0.1)	0.1 (0.1)
Day 7 (n=10, 3)	0.0 (0.2)	0.0 (0.1)

9. Secondary Outcome

Title	Plasma Erythropoietin (EPO) Levels - Change From Baseline
Description	Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. EPO can be detected and measured in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline and Day 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Mean (Standard Deviation) [U/L]	-5.9 (50.3)	-15.1 (20.4)

10. Secondary Outcome

Title	Hematocrit Levels - Change From Baseline
Description	Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	0.006 (0.011)	-0.002 (0.007)
Day 7 (n=9, 3)	0.007 (0.013)	0.020 (0.010)
Day 14 (n=8, 2)	0.003 (0.013)	-0.006 (0.015)
Day 28 (n=8, 2)	0.011 (0.012)	0.006 (0.007)

11. Secondary Outcome

Title	Lactate Dehydrogenase (LDH) Levels - Change From Baseline
Description	LDH levels were measured as a biomarker for intravascular hemolysis. The results are based on the LDH Total measurement. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	60 (107)	0 (197)
Day 7 (n=9, 3)	71 (101)	-6 (167)
Day 14 (n=8, 2)	4 (100)	689 (1142)
Day 28 (n=8, 2)	29 (110)	-69 (91)

12. Secondary Outcome

Title	Hemoglobin Levels - Change From Baseline
Description	A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	0 (5)	-3 (7)
Day 4 (n=10, 3)	1 (7)	3 (3)
Day 7 (n=10, 3)	-1 (5)	3 (2)
Day 14 (n=8, 2)	-2 (5)	-6 (1)
Day 21 (n=2, 0)	1 (4)	NA (NA)
Day 28 (n=10, 2)	0 (4)	-2 (5)

13. Secondary Outcome

Title	Reticulocyte Percent- Change From Baseline
Description	Category title includes number of participants with available data (n) for participants treated with study product.
Time Frame	At baseline, Day 1 and Day 7 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Arm/Group Title	Treatment With Study Product
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days
Measure Participants	2
Day 1 (n=2)	-0.46 (0.18)
Day 7 (n=1)	NA (NA)

14. Secondary Outcome

Title	Direct Bilirubin - Change From Baseline
Description	Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14, Day 21 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	0 (0)	0 (0)
Day 4 (n=10, 3)	0 (0)	0 (0)
Day 7 (n=10, 3)	0 (0)	0 (0)
Day 14 (n= 8, 2)	0 (0)	0 (0)
Day 21 (n=2, 0)	0 (0)	NA (NA)
Day 28 (n=10, 2)	0 (0)	0 (0)

15. Secondary Outcome

Title	LDH Isoform - Change From Baseline
Description
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description
Summary tables for this outcome measure were not done as baseline data missing. Study terminated early.

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	0	0

16. Secondary Outcome

Title	C Reactive Protein Levels - Change From Baseline
Description	Category title includes number of participants with available data (n) for participants treated with study product.
Time Frame	At baseline, Day 1 and Day 7 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Arm/Group Title	Treatment With Study Product
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days
Measure Participants	2
Day 1 (n=2)	-1.2 (3.0)
Day 7 (n=1)	NA (NA)

17. Secondary Outcome

Title	Serum Ferritin Levels - Change From Baseline
Description
Time Frame	At baseline, Day 1 and Day 7 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Arm/Group Title	Treatment With Study Product
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days
Measure Participants	2
Day 1	-4.9 (0.1)
Day 7	NA (NA)

18. Secondary Outcome

Title	N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline
Description	Category title includes number of participants with available data (n) for participants treated with study product.
Time Frame	At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.

Arm/Group Title	Treatment With Study Product
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days
Measure Participants	9
Day 1 (n=7)	6 (15)
Day 7 (n=6)	6 (97)
Day 14 (n=6)	32 (25)
Day 28 (n=7)	1 (55)

19. Secondary Outcome

Title	Body Weight - Change From Baseline
Description	A negative change in body weight denotes a weight decrease, a positive change in body weight denotes a weight increase. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 1 (n=11, 3)	-0.2 (0.7)	-0.6 (0.4)
Day 4 (n=10, 3)	-0.3 (1.6)	-0.4 (0.8)
Day 7 (n=10, 3)	-0.5 (1.6)	-0.7 (1.3)
Day 14 (n=8, 2)	1.1 (0.8)	0.8 (0.7)
Day 21 (n=6, 2)	0.1 (1.4)	0.5 (0.1)
Day 28 (n=10, 2)	0.6 (0.9)	0.4 (0.4)

20. Secondary Outcome

Title	Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline
Description	Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 4 (n=9, 3)	-8.5 (38.2)	20.6 (8.0)
Day 7 (n=9, 3)	36.9 (44.6)	28.3 (24.3)
Day 14 (n=8, 2)	-0.1 (31.5)	4.1 (6.1)
Day 28 (n=8, 2)	-14.9 (41.2)	-8.2 (8.2)

21. Secondary Outcome

Title	Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline
Description	Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1.
Time Frame	Prior to dosing at baseline and on Day 49 of the post-treatment observation period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	8	2
Mean (Standard Deviation) [meters]	-20.6 (41.3)	-1.1 (3.5)

22. Secondary Outcome

Title	Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28)
Description	Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results.
Time Frame	On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	8	2
Mean (Standard Deviation) [meters]	-5.6 (63.6)	7.2 (4.7)

23. Secondary Outcome

Title	Exercise Tolerance: Cardiopulmonary Exercise Test [CPET]
Description	CPET was optional, based on capacity of participant to complete the test.
Time Frame	On last day of double-blind treatment period (Day 28)

Outcome Measure Data

Analysis Population Description
Following an external review and report of CPET capabilities of the external service provider, all CPET testing was suspended and the decision made to not collect or analyze CPET data.

Arm/Group Title	Overall Study Arm
Arm/Group Description
Measure Participants	0

24. Secondary Outcome

Title	Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline
Description	Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. No values available for placebo group for Day 28. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 7 (n=10, 3)	0 (1)	0 (0)
Day 14 (n=9, 2)	0 (0)	0 (0)
Day 21 (n=8, 2)	0 (1)	0 (0)
Day 28 (n=9, 1)	0 (1)	NA (NA)

25. Secondary Outcome

Title	Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline
Description	Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Day 35 (n=8, 2)	0 (1)	0 (0)
Day 42 (n=10, 2)	0 (1)	0 (0)
Day 49 (n=8, 2)	0 (1)	0 (0)

26. Secondary Outcome

Title	Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period
Description	Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline was defined as the most recent value obtained on the last day of the double-blind treatment period. Categories contain Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Day 35 (n=8, 2)	0 (0)	0 (0)
Day 42 (n=10, 2)	0 (0)	0 (0)
Day 49 (n=8, 2)	0 (0)	0 (0)

27. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 7 (n=11, 3)	1.682 (3.482)	4.533 (4.536)
Day 14 (n=10, 2)	-0.850 (1.255)	-0.650 (0.071)
Day 21 (n=8, 2)	-0.825 (1.302)	-0.650 (0.071)
Day 28 (n=9, 2)	0.689 (1.279)	-0.650 (0.071)

28. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21. and Day 28.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Mean (Standard Deviation) [NPRS score*week]	-2.352 (2.674)	-3.229 (2.847)

29. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Day 35 (n=8, 2)	-4.675 (3.729)	-7.750 (1.202)
Day 42 (n=10, 2)	-2.830 (5.494)	-7.750 (1.202)
Day 49 (n=9, 2)	-3.089 (6.049)	-8.15 (0.212)

30. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 49.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Mean (Standard Deviation) [NPRS score*week]	-2.836 (3.637)	-6.118 (0.874)

31. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28)
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Day 35 (n=8, 2)	-3.425 (3.302)	-7.750 (1.202)
Day 42 (n=10, 2)	-1.830 (4.905)	-7.750 (1.202)
Day 49 (n=9, 2)	-1.978 (5.479)	-8.150 (0.212)

32. Secondary Outcome

Title	Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC
Description	Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living [ADLs]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Area under the curve (AUC) was computed using change from baseline (Day 28) in weekly average values at Day 35, Day 42 and Day 49.
Time Frame	Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	10	2
Mean (Standard Deviation) [NPRS score*week]	-2.836 (3.637)	-6.118 (0.874)

33. Secondary Outcome

Title	Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline
Description	Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline, Day 7 and Day 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 7 (n=10, 3)	-0.4 (2.3)	-3.0 (3.3)
Day 28 (n=8, 2)	-0.6 (1.2)	-1.3 (3.2)

34. Secondary Outcome

Title	Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline
Description	Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline, Day 7 and Day 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 7 (n=10, 3)	-1 (3)	0 (0)
Day 28 (n=8, 2)	-1 (3)	1 (1)

35. Secondary Outcome

Title	Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline
Description	Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Time Frame	At baseline and Day 49 during the post-treatment observation period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	8	2
Mean (Standard Deviation) [score on a scale]	-1 (5)	0 (0)

36. Secondary Outcome

Title	Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline
Description	Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time Frame	At baseline, Day 7 and Day 28 during the double-blind treatment period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Treatment With Study Product	Treatment With Placebo
Arm/Group Description	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of Aes-103 for 28 days	Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of 1,000 mg of placebo for 28 days
Measure Participants	11	3
Day 7 (n=10, 3)	0 (2)	0 (0)
Day 28 (n=8, 2)	1 (2)	0 (0)

37. Secondary Outcome

Title	Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline
Description	Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Time Frame	At baseline and Day 49 during the post-treatment observation period

Outcome Measure Data

Analysis Population Description
Participants who provided baseline data and at least one other data point for this outcome measure.

Arm/Group Title	Post-treatment With Study Product Observation Period	Post-treatment With Placebo Observation Period
Arm/Group Description	Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) was received	Participants underwent a post-treatment observation period of 21 days during which no study product (placebo) was received
Measure Participants	8	2
Mean (Standard Deviation) [score on a scale]	0 (1)	0 (0)

38. Secondary Outcome

Title	Analgesic Use
Description	Analgesic use assessed with pain levels by numerical pain rating scale (NPRS) and brief pain inventory (BPI).
Time Frame	Throughout the study period (approximately 9 weeks)

Outcome Measure Data

Analysis Population Description
Data not collected for this outcome measure. Study terminated early.

Arm/Group Title	Overall Study Arm
Arm/Group Description
Measure Participants	0

39. Secondary Outcome

Title	Reduction in Sickle Cell-specific Complications
Description
Time Frame	Throughout the study period (approximately 9 weeks)

Outcome Measure Data

Analysis Population Description
Data not collected for this outcome measure. Study terminated early.

Arm/Group Title	Overall Study Arm
Arm/Group Description
Measure Participants	0

Adverse Events

	Placebo lead-in Period		Double-blind Treatment Period		Post-treatment Observation Period
Time Frame	Throughout study period (approximately 9 weeks)
Adverse Event Reporting Description	Summary tables for Adverse Events were provided per study period i.e. Placebo Lead-in Period, Double-blind treatment period and Post-treatment observation period. No breakdown of AEs with study product and placebo were provided as study terminated early.

Arm/Group Title	Placebo lead-in Period		Double-blind Treatment Period		Post-treatment Observation Period
Arm/Group Description	Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo (Day -14 to Day -1)		Participants randomized 3:1 (Aes-103 to placebo) to receive 4 times daily dosing of either 1,000 mg of Aes-103 (study product) or placebo for 28 days (Day 1 to Day 28)		Participants underwent a post-treatment observation period of 21 days during which no study product (Aes-103) or placebo was received (Day 29 to Day 49)
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo lead-in Period		Double-blind Treatment Period		Post-treatment Observation Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)		0/14 (0%)		1/12 (8.3%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	2/23 (8.7%)	2	0/14 (0%)	0	0/12 (0%)	0
Sickle cell anaemia	0/23 (0%)	0	0/14 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Placebo lead-in Period		Double-blind Treatment Period		Post-treatment Observation Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)		12/14 (85.7%)		4/12 (33.3%)
Cardiac disorders
Atrioventricular block first degree	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Congenital, familial and genetic disorders
Sickle cell anaemia	5/23 (21.7%)	5	5/14 (35.7%)	6	2/12 (16.7%)	2
Eye disorders
Diplopia	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Abdominal distension	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Abdominal pain	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Abdominal pain upper	2/23 (8.7%)	2	0/14 (0%)	0	0/12 (0%)	0
Diarrhoea	1/23 (4.3%)	1	1/14 (7.1%)	1	0/12 (0%)	0
Dyspepsia	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Faeces discoloured	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Flatulence	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Nausea	3/23 (13%)	3	4/14 (28.6%)	4	0/12 (0%)	0
Toothache	1/23 (4.3%)	1	1/14 (7.1%)	1	1/12 (8.3%)	1
Vomiting	1/23 (4.3%)	1	1/14 (7.1%)	1	0/12 (0%)	0
General disorders
Fatigue	0/23 (0%)	0	1/14 (7.1%)	2	0/12 (0%)	0
Pain	1/23 (4.3%)	1	1/14 (7.1%)	1	0/12 (0%)	0
Infections and infestations
Lower respiratory tract infection	2/23 (8.7%)	2	0/14 (0%)	0	0/12 (0%)	0
Rhinitis	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Upper respiratory tract infection	0/23 (0%)	0	2/14 (14.3%)	2	0/12 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Investigations
Electrocardiogram T wave inversion	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Liver function test abnormal	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Transaminases increased	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Metabolism and nutrition disorders
Increased appetite	2/23 (8.7%)	2	0/14 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/23 (4.3%)	1	1/14 (7.1%)	1	0/12 (0%)	0
Muscle spasms	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Musculoskeletal stiffness	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Pain in extremity	1/23 (4.3%)	1	0/14 (0%)	0	0/12 (0%)	0
Nervous system disorders
Dysgeusia	13/23 (56.5%)	13	1/14 (7.1%)	1	0/12 (0%)	0
Headache	5/23 (21.7%)	7	6/14 (42.9%)	6	1/12 (8.3%)	1
Migraine	1/23 (4.3%)	1	0/14 (0%)	0	1/12 (8.3%)	2
Reproductive system and breast disorders
Dysmenorrhoea	0/23 (0%)	0	2/14 (14.3%)	2	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/23 (0%)	0	1/14 (7.1%)	1	0/12 (0%)	0
Oropharyngeal pain	1/23 (4.3%)	1	1/14 (7.1%)	1	0/12 (0%)	0

Limitations/Caveats

PK data not determined as the assay collection method was found to be faulty rendering all samples unevaluable. Study was terminated early by the Sponsor due to unblinding between study drug and placebo groups at the subject, site and Sponsor levels.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.

Results Point of Contact

Name/Title	Study Director
Organization	Shire
Phone	+1 866 842 5335
Email	ClinicalTransparency@shire.com

Responsible Party:

Baxalta now part of Shire

ClinicalTrials.gov Identifier:

NCT01987908

Other Study ID Numbers:

Aes-103-003
321401
2013-001534-18

First Posted:

Nov 20, 2013

Last Update Posted:

May 25, 2021

Last Verified:

May 1, 2021

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

Study Details

Study Description

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Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

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Inclusion Criteria:

Exclusion Criteria:

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Other (Not Including Serious) Adverse Events

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Results Point of Contact