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

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ClinicalTrials.gov Identifier: NCT01987908
Recruitment Status : Terminated (Study was terminated early by the Sponsor due to unblinding between study drug and placebo groups at the subject, site and Sponsor levels.)
First Posted : November 20, 2013
Results First Posted : March 24, 2017
Last Update Posted : October 23, 2017
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Sickle Cell Disease
Interventions Drug: Aes-103
Other: Placebo
Enrollment 35

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 Details 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
Hide 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
Reason Not Completed
Adverse Event             2             0             0
Physician Decision             2             0             0
Withdrawal by Subject             1             0             0
Other: Study Termination by Sponsor             4             0             0
Period Title: Treatment Period
Started 0 11 3
Completed 0 10 2
Not Completed 0 1 1
Reason Not Completed
Adverse Event             0             1             1
Period Title: Post-Treatment Observation Period
Started 0 10 2
Completed 0 7 2
Not Completed 0 3 0
Reason Not Completed
Other: Study Termination by Sponsor             0             2             0
Other: Bad Veins             0             1             0
Arm/Group Title Placebo lead-in Period
Hide Arm/Group Description Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
Out of the participants who enrolled in the study, only participants who passed the screen and were randomized were entered in the Placebo Lead-in Period.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants
28  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
13
  56.5%
Male
10
  43.5%
1.Primary Outcome
Title Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo All Treated Participants
Hide 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
Overall Number of Participants Analyzed 11 3 14
Measure Type: Number
Unit of Measure: participants
Treatment-emergent AEs 9 3 12
Related AEs 8 2 10
Serious AEs 0 0 0
Severe AEs 0 0 0
AEs leading to discontinuation 1 1 2
AEs leading to death 0 0 0
Sickle-cell specific complications 4 1 5
2.Primary Outcome
Title Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo lead-in Period
Hide Arm/Group Description:
Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: participants
Treatment-emergent AEs 21
Related AEs 12
Serious AEs 2
Severe AEs 2
AEs leading to discontinuation 2
AEs leading to death 0
Sickle cell-specific complications 2
3.Primary Outcome
Title Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period
Hide 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)
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[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
Hide 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
Overall Number of Participants Analyzed 10 2 12
Measure Type: Number
Unit of Measure: participants
Treatment-emergent AEs 4 0 4
Related AEs 2 0 2
Serious AEs 1 0 1
Severe AEs 1 0 1
AEs leading to discontinuation 0 0 0
AEs leading to death 0 0 0
Sickle cell-specific complications 2 0 2
4.Primary Outcome
Title Number of Participants With Sickle-Cell Disease-related Symptoms
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 23 11 3 10 2
Measure Type: Number
Unit of Measure: participants
Abdominal Pain - Sickle Pain 0 1 0 0 0
Exacerbation of Sickle Cell (SC) Disease Pain 1 1 0 1 0
SC Disease Related Pain 0 3 0 1 0
SC Pain 3 3 1 1 0
Intermittent SC Pain 1 0 0 0 0
SC Crisis 1 0 0 0 0
Vaso-Occlusive Crisis caused by Chest Infection 1 0 0 0 0
5.Primary Outcome
Title Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations
Hide 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)
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Hide 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
Hide 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)
Overall Number of Participants Analyzed 23 11 3 12
Measure Type: Number
Unit of Measure: clinically significant observations
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
Hide 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)
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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
Hide Arm/Group Description:
Data not collected
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: percent saturation
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: U/L
-5.9  (50.3) -15.1  (20.4)
10.Secondary Outcome
Title Hematocrit Levels - Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: L/L
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: U/L
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: g/L
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 [1]   (NA)
Day 28 (n=10, 2) 0  (4) -2  (5)
[1]
Data not collected.
13.Secondary Outcome
Title Reticulocyte Percent- Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: percent
Day 1 (n=2) -0.46  (0.18)
Day 7 (n=1) NA [1]   (NA)
[1]
When number of participants is less than 2, summary statistics are not computed.
14.Secondary Outcome
Title Direct Bilirubin - Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: mircomoles/L
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 [1]   (NA)
Day 28 (n=10, 2) 0  (0) 0  (0)
[1]
Data not collected.
15.Secondary Outcome
Title LDH Isoform - Change From Baseline
Hide Description [Not Specified]
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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title C Reactive Protein Levels - Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: mg/L
Day 1 (n=2) -1.2  (3.0)
Day 7 (n=1) NA [1]   (NA)
[1]
When number of participants is less than 2, summary statistics are not computed.
17.Secondary Outcome
Title Serum Ferritin Levels - Change From Baseline
Hide Description [Not Specified]
Time Frame At baseline, Day 1 and Day 7 during the double-blind treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: mircograms/L
Day 1 -4.9  (0.1)
Day 7 NA [1]   (NA)
[1]
When number of participants is less than 2, summary statistics are not computed.
18.Secondary Outcome
Title N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: pmol/L
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: kg
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: meters
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
Hide 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
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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
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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
Overall Number of Participants Analyzed 8 2
Mean (Standard Deviation)
Unit of Measure: 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)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 8 2
Mean (Standard Deviation)
Unit of Measure: meters
-5.6  (63.6) 7.2  (4.7)
23.Secondary Outcome
Title Exercise Tolerance: Cardiopulmonary Exercise Test [CPET]
Hide 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)
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Hide 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
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[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline
Hide 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
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
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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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
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 [1]   (NA)
[1]
When number of participants is less than 2, summary statistics are not computed.
25.Secondary Outcome
Title Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment With Study Product Treatment With Placebo
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: 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)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Post-treatment With Study Product Observation Period Post-treatment With Placebo Observation Period
Hide 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
Overall Number of Participants Analyzed 10 2
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
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Hide 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
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 8 2
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 8 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
0  (1) 0  (0)
38.Secondary Outcome
Title Analgesic Use
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data not collected for this outcome measure. Study terminated early.
Arm/Group Title Overall Study Arm
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
39.Secondary Outcome
Title Reduction in Sickle Cell-specific Complications
Hide Description [Not Specified]
Time Frame Throughout the study period (approximately 9 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data not collected for this outcome measure. Study terminated early.
Arm/Group Title Overall Study Arm
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
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
Hide 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
Placebo lead-in Period Double-blind Treatment Period Post-treatment Observation Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide 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 (8.70%)      0/14 (0.00%)      1/12 (8.33%)    
Congenital, familial and genetic disorders       
Sickle cell anaemia with crisis  1  2/23 (8.70%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Sickle cell anaemia  1  0/23 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (91.30%)      12/14 (85.71%)      4/12 (33.33%)    
Cardiac disorders       
Atrioventricular block first degree * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Congenital, familial and genetic disorders       
Sickle cell anaemia * 1  5/23 (21.74%)  5 5/14 (35.71%)  6 2/12 (16.67%)  2
Eye disorders       
Diplopia * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Gastrointestinal disorders       
Abdominal discomfort * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Abdominal distension * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Abdominal pain upper * 1  2/23 (8.70%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Diarrhoea * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
Dyspepsia * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Faeces discoloured * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Flatulence * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Nausea * 1  3/23 (13.04%)  3 4/14 (28.57%)  4 0/12 (0.00%)  0
Toothache * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 1/12 (8.33%)  1
Vomiting * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
General disorders       
Fatigue * 1  0/23 (0.00%)  0 1/14 (7.14%)  2 0/12 (0.00%)  0
Pain * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
Infections and infestations       
Lower respiratory tract infection * 1  2/23 (8.70%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Rhinitis * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Upper respiratory tract infection * 1  0/23 (0.00%)  0 2/14 (14.29%)  2 0/12 (0.00%)  0
Injury, poisoning and procedural complications       
Ligament sprain * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Investigations       
Electrocardiogram T wave inversion * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Liver function test abnormal * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Transaminases increased * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Metabolism and nutrition disorders       
Increased appetite * 1  2/23 (8.70%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
Muscle spasms * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal stiffness * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pain in extremity * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders       
Dysgeusia * 1  13/23 (56.52%)  13 1/14 (7.14%)  1 0/12 (0.00%)  0
Headache * 1  5/23 (21.74%)  7 6/14 (42.86%)  6 1/12 (8.33%)  1
Migraine * 1  1/23 (4.35%)  1 0/14 (0.00%)  0 1/12 (8.33%)  2
Reproductive system and breast disorders       
Dysmenorrhoea * 1  0/23 (0.00%)  0 2/14 (14.29%)  2 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/23 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Oropharyngeal pain * 1  1/23 (4.35%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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: Clinical Trial Registries and Results Disclosure
Organization: Baxalta US Inc.
Responsible Party: Shire ( Baxalta now part of Shire )
ClinicalTrials.gov Identifier: NCT01987908     History of Changes
Other Study ID Numbers: Aes-103-003
321401 ( Other Identifier: Baxalta )
First Submitted: October 29, 2013
First Posted: November 20, 2013
Results First Submitted: June 21, 2016
Results First Posted: March 24, 2017
Last Update Posted: October 23, 2017