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

This study has been terminated.
(Study was terminated early by the Sponsor due to unblinding between study drug and placebo groups at the subject, site and Sponsor levels.)
Sponsor:
Information provided by (Responsible Party):
Baxalta US Inc.
ClinicalTrials.gov Identifier:
NCT01987908
First received: October 29, 2013
Last updated: February 3, 2017
Last verified: November 2016
Results First Received: June 21, 2016  
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

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
Placebo lead-in Period Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo
Treatment With Study Product 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
Treatment With 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 placebo for 28 days during the double-blind treatment period

Participant Flow for 3 periods

Period 1:   Placebo Lead-in Period
    Placebo lead-in Period   Treatment With Study Product   Treatment With Placebo
STARTED   23   0   0 
COMPLETED   14   0   0 
NOT COMPLETED   9   0   0 
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 2:   Treatment Period
    Placebo lead-in Period   Treatment With Study Product   Treatment With Placebo
STARTED   0   11   3 
COMPLETED   0   10   2 
NOT COMPLETED   0   1   1 
Adverse Event                0                1                1 

Period 3:   Post-Treatment Observation Period
    Placebo lead-in Period   Treatment With Study Product   Treatment With Placebo
STARTED   0   10   2 
COMPLETED   0   7   2 
NOT COMPLETED   0   3   0 
Other: Study Termination by Sponsor                0                2                0 
Other: Bad Veins                0                1                0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo lead-in Period Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo

Baseline Measures
   Placebo lead-in Period 
Overall Participants Analyzed 
[Units: Participants]
 23 
Age 
[Units: Years]
Mean (Standard Deviation)
 28  (7) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      13  56.5% 
Male      10  43.5% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period   [ Time Frame: Double-blind treatment period of 28 days (Day 1 to Day 28) ]

2.  Primary:   Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period   [ Time Frame: Placebo lead-in period of 14 days (Day -14 to Day -1) ]

3.  Primary:   Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period   [ Time Frame: Post-treatment observation period of 21 days (Day 29 to Day 49) ]

4.  Primary:   Number of Participants With Sickle-Cell Disease-related Symptoms   [ 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) ]

5.  Primary:   Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations   [ Time Frame: Throughout the study period (approximately 9 weeks) ]

6.  Primary:   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   [ 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) ]

7.  Secondary:   Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline   [ 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 ]

8.  Secondary:   Oxygen Binding p50/p20 Value - Change From Baseline   [ Time Frame: During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7 ]

9.  Secondary:   Plasma Erythropoietin (EPO) Levels - Change From Baseline   [ Time Frame: At baseline and Day 28 during the double-blind treatment period ]

10.  Secondary:   Hematocrit Levels - Change From Baseline   [ 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 ]

11.  Secondary:   Lactate Dehydrogenase (LDH) Levels - Change From Baseline   [ 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 ]

12.  Secondary:   Hemoglobin Levels - Change From Baseline   [ 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 ]

13.  Secondary:   Reticulocyte Percent- Change From Baseline   [ Time Frame: At baseline, Day 1 and Day 7 during the double-blind treatment period ]

14.  Secondary:   Direct Bilirubin - Change From Baseline   [ 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 ]

15.  Secondary:   LDH Isoform - Change From Baseline   [ 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 ]

16.  Secondary:   C Reactive Protein Levels - Change From Baseline   [ Time Frame: At baseline, Day 1 and Day 7 during the double-blind treatment period ]

17.  Secondary:   Serum Ferritin Levels - Change From Baseline   [ Time Frame: At baseline, Day 1 and Day 7 during the double-blind treatment period ]

18.  Secondary:   N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline   [ Time Frame: At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period ]

19.  Secondary:   Body Weight - Change From Baseline   [ 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 ]

20.  Secondary:   Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline   [ 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 ]

21.  Secondary:   Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline   [ Time Frame: Prior to dosing at baseline and on Day 49 of the post-treatment observation period ]

22.  Secondary:   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)   [ Time Frame: On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period ]

23.  Secondary:   Exercise Tolerance: Cardiopulmonary Exercise Test [CPET]   [ Time Frame: On last day of double-blind treatment period (Day 28) ]

24.  Secondary:   Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline   [ Time Frame: At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period ]

25.  Secondary:   Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline   [ Time Frame: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period ]

26.  Secondary:   Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period   [ Time Frame: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period ]

27.  Secondary:   Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline   [ 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 ]

28.  Secondary:   Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC   [ 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 ]

29.  Secondary:   Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline   [ Time Frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments ]

30.  Secondary:   Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC   [ Time Frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments ]

31.  Secondary:   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)   [ Time Frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments ]

32.  Secondary:   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   [ Time Frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments ]

33.  Secondary:   Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline   [ Time Frame: At baseline, Day 7 and Day 28 during the double-blind treatment period ]

34.  Secondary:   Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline   [ Time Frame: At baseline, Day 7 and Day 28 during the double-blind treatment period ]

35.  Secondary:   Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline   [ Time Frame: At baseline and Day 49 during the post-treatment observation period ]

36.  Secondary:   Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline   [ Time Frame: At baseline, Day 7 and Day 28 during the double-blind treatment period ]

37.  Secondary:   Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline   [ Time Frame: At baseline and Day 49 during the post-treatment observation period ]

38.  Secondary:   Analgesic Use   [ Time Frame: Throughout the study period (approximately 9 weeks) ]

39.  Secondary:   Reduction in Sickle Cell-specific Complications   [ Time Frame: Throughout the study period (approximately 9 weeks) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Registries and Results Disclosure
Organization: Baxalta US Inc.
e-mail: ClinicalTrialsDisclosure@baxalta.com



Responsible Party: Baxalta US Inc.
ClinicalTrials.gov Identifier: NCT01987908     History of Changes
Other Study ID Numbers: Aes-103-003
321401 ( Other Identifier: Baxalta )
Study First Received: October 29, 2013
Results First Received: June 21, 2016
Last Updated: February 3, 2017