Clinical Trial Results:
A Phase 4, single-arm, open-label safety and efficacy study of Aldurazyme® (laronidase) as enzyme replacement therapy in participants with Mucopolysaccharidosis I (MPS I) in China
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Summary
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EudraCT number |
2023-001027-16 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
26 Jul 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Feb 2024
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First version publication date |
01 Feb 2024
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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 |
LPS16578
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05134571 | ||
WHO universal trial number (UTN) |
U1111-1260-3947 | ||
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Sponsors
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Sponsor organisation name |
Sanofi B.V.
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Sponsor organisation address |
Paasheuvelweg 25, Amsterdam, Netherlands, 1105 BP
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Public contact |
Trial Transparency Team, Sanofi-Aventis Recherche & Developpement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi-Aventis Recherche & Developpement, 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 |
14 Aug 2023
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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 |
26 Jul 2023
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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 |
• To evaluate the safety and tolerability of aldurazyme in Chinese mucopolysaccharidosis I (MPS I) participants.
• To evaluate the efficacy of aldurazyme on urinary glycosaminoglycans (uGAGs) after 26 weeks of treatment in Chinese MPS I participants.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Oct 2021
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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 |
China: 12
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Worldwide total number of subjects |
12
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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) |
7
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
4
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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 5 active centers in China between 28 October 2021 and 26 July 2023. A total of 12 subjects were screened in this study and there were no screening failures. | ||||||
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Pre-assignment
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Screening details |
A total of 12 subjects were treated in the study. This was a single-arm, open-label 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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Aldurazyme | ||||||
Arm description |
Subjects were treated with aldurazyme 100 units per kilogram (U/kg) of body weight intravenous (IV) infusion once weekly (QW) up to 26 weeks. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Aldurazyme
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Investigational medicinal product code |
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Other name |
Laronidase
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Aldurazyme 100 U/kg of body weight through IV infusion QW up to 26 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Aldurazyme
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Reporting group description |
Subjects were treated with aldurazyme 100 units per kilogram (U/kg) of body weight intravenous (IV) infusion once weekly (QW) up to 26 weeks. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aldurazyme
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Reporting group description |
Subjects were treated with aldurazyme 100 units per kilogram (U/kg) of body weight intravenous (IV) infusion once weekly (QW) up to 26 weeks. | ||
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End point title |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) [1] | ||||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period [that is, from the time of first dose of study intervention up to 7 days after the last administration of the study intervention]. Results are based on the safety analysis set which included all enrolled subjects who received at least 1 dose of study intervention.
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End point type |
Primary
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End point timeframe |
From first dose administration (Day 1) up to Week 27
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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: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Laboratory Parameters [2] | ||||||||||||||||||
End point description |
Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Results are based on the safety analysis set which included all enrolled subjects who received at least 1 dose of study intervention.
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End point type |
Primary
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End point timeframe |
From first dose administration (Day 1) up to Week 27
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| Notes [2] - 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: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) [3] | ||||||||||||||||||||||
End point description |
Single 12-lead ECGs were recorded after at least 10 minutes rest in the supine position using an electrocardiographic device. The following were assessed: heart rate (HR), PR interval, QRS duration, QT interval and corrected QTc (method unspecified). Results are based on the safety analysis set which included all enrolled subjects who received at least 1 dose of study intervention. Here, n= number of subjects analyzed for each parameter.
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End point type |
Primary
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End point timeframe |
From first dose administration (Day 1) up to Week 27
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| Notes [3] - 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: Only descriptive statistical analysis was performed for the primary endpoint. |
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| Notes [4] - n= 4 for HR:High, >= Grade 1 and Grade 2; HR:High and increase from baseline >= Grade 1 and Grade 2. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs [5] | ||||||||||||||||||||||||
End point description |
Subjects vital signs were examined to determine the abnormalities. Vital signs included HR, systolic blood pressure (SBP) and diastolic blood pressure (DBP), weight, respiratory rate, temperature and height. Results are based on the safety analysis set which included all enrolled subjects who received at least 1 dose of study intervention. Here, n= number of subjects analyzed for each parameter.
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End point type |
Primary
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End point timeframe |
From first dose administration (Day 1) up to Week 27
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| Notes [5] - 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: Only descriptive statistical analysis was performed for the primary endpoint. |
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| Notes [6] - n= 4 for HR, weight: Increase from baseline. n= 8 for respiratory rate. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percent Change From Baseline in Urinary Glycosaminoglycan (uGAGs) at Week 26 [7] | ||||||||
End point description |
Urine samples collected and performed analysis at central lab to determine the uGAG level. The missing value was imputed by carrying forward the last uGAG value [last observation carried forward (LOCF) method] observed during the on-treatment period. Results are based on the modified intent-to-treat (mITT) analysis set which included all enrolled subjects who received at least 1 dose of study intervention and with an evaluable primary efficacy endpoint.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) and Week 26
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| Notes [7] - 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: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in uGAGs up to Week 20 | ||||||||||||||||||
End point description |
Urine samples collected and performed analysis at central lab to determine the uGAG level. Results are based on the mITT analysis set which included all enrolled subjects who received at least 1 dose of study intervention and with an evaluable primary efficacy endpoint. Here, n= number of subjects analyzed at specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Weeks 2, 4, 8, 12 and 20
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Absolute Change From Baseline in uGAGs up to Week 26 | ||||||||||||||||||||
End point description |
Urine samples collected and performed analysis at central lab to determine the uGAG level. The missing value was imputed by carrying forward the last uGAG value (LOCF method) observed during the on-treatment period. Results are based on the mITT analysis set which included all enrolled subjects who received at least 1 dose of study intervention and with an evaluable primary efficacy endpoint. Here, n= number of subjects analyzed at specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Weeks 2, 4, 8, 12, 20 and 26
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Percent Change From Baseline in Liver Volume at Week 26 | ||||||||
End point description |
Liver volume was measured by abdominal B type ultrasound examination. Results are based on the mITT analysis set which included all enrolled subjects who received at least 1 dose of study intervention and with an evaluable primary efficacy endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Week 26
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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 |
TEAEs data was collected from first dose administration (Day 1) up to Week 27.
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Adverse event reporting additional description |
Analysis was performed on the safety analysis set.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Aldurazyme
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Reporting group description |
Subjects were treated with aldurazyme 100 U/kg of body weight IV infusion QW up to 26 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| None reported | |||
