Clinical Trial Results:
Evaluation of Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta (The INFORM Study)
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Summary
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EudraCT number |
2015-000697-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 Mar 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
23 May 2016
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First version publication date |
08 Jul 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AGAL19412
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01650779 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Genzyme Corporation
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Sponsor organisation address |
500 Kendall Street, Cambridge, MA, United States, 02142
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jun 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Mar 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This is an exploratory study to evaluate changes in glycosphingolipid levels and other (exploratory) Fabry disease parameters in male Fabry disease subjects who were previously treated with agalsidase alfa (Replagal®) 0.2 milligram per kilogram (mg/kg) every two weeks (q2w) and who were being switched to agalsidase beta (Fabrazyme®) 1.0 mg/kg q2w.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency.
Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
2
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
11
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 6 centers in the United States of America between April 30, 2012 and March 15, 2013. | ||||||||||
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Pre-assignment
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Screening details |
A total of 16 subjects were screened of which 1 subject was screen failure. A total of 15 subjects were enrolled in this study. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Agalsidase Beta | ||||||||||
Arm description |
Commercially available agalsidase beta up to Month 6. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Agalsidase beta
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Investigational medicinal product code |
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Other name |
Fabrazyme®
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Pharmaceutical forms |
Powder for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1 mg/kg every two weeks (q2w).
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Baseline characteristics reporting groups
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Reporting group title |
Agalsidase Beta
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Reporting group description |
Commercially available agalsidase beta up to Month 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Agalsidase Beta
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Reporting group description |
Commercially available agalsidase beta up to Month 6. | ||
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End point title |
Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 [1] | ||||||||||||||
End point description |
Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers. All enrolled subjects were included in the analysis. Here, 'n' signifies subjects with plasma Lyso-GL-3 assessment at the specified time point.
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End point type |
Primary
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End point timeframe |
Baseline, Month 2, 4, 6
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to system limitations statistical analysis cannot be presented for Single Arm Study. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 | ||||||||||||||
End point description |
Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. All enrolled subjects were included in the analysis. Here, 'n' signifies subjects with plasma GL-3 assessment at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 2, 4, 6
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 | ||||||||||||||
End point description |
Percent change from baseline = ([post-baseline value minus baseline value] divided by [baseline value]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. All enrolled subjects were included in the analysis. Here, 'n' signifies subjects with urine GL-3 assessment at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 2, 4, 6
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 | ||||||||
End point description |
Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual subject listing only. Analysis of this data was planned only if baseline data was collected on a large number of enrolled subjects. This was not the case and therefore interpretation of these results were not possible.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 2, 4, 6
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| Notes [2] - Explanation is provided in measure description. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to end of study (Month 6) or early withdrawal.
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Adverse event reporting additional description |
All enrolled subjects were included in the analysis.
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Assessment type |
Non-systematic | ||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Agalsidase Beta
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Reporting group description |
Commercially available agalsidase beta up to Month 6. | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| This is considered to be an exploratory study for the following reasons: it was based on a small number of subjects and has been designed as an open-label, single-arm study as opposed to a two-arm crossover design. | |||
