Clinical Trial Results:
A Single arm, Prospective, Open Label, Multicenter Study to Evaluate Efficacy and Safety of One-Year Maximum Dosage in Chinese Label of Imiglucerase Treatment in Chinese Patients who are Diagnosed as Gaucher Disease Type Ⅲ
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Summary
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EudraCT number |
2024-000041-27 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 Oct 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Apr 2024
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First version publication date |
25 Apr 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 |
LPS16031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04656600 | ||
WHO universal trial number (UTN) |
U1111-1244-1166 | ||
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Sponsors
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Sponsor organisation name |
SANOFI (CHINA) INVESTMENT CO., LTD
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Sponsor organisation address |
7F of HP Building, No.112 Jianguo Road, Chaoyang District, Beijing, China, 100022
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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 |
07 Dec 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 |
12 Oct 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 efficacy on hematologic manifestations of Cerezyme treatment in Chinese participants who were diagnosed as Gaucher disease type Ⅲ and to evaluate the safety profile of Cerezyme in maximum dose in the label (60 units per kilogram [U/kg], intravenous [IV] biweekly) in Chinese participants.
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric particpants. The parent(s) or guardian(s) as well as 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 minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anaesthesia may have been used to minimise distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Mar 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) |
2
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Adolescents (12-17 years) |
6
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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 centers in China. A total of 13 participants were screened from 02 March 2021 to 15 September 2022, of which 1 was screen failure. | ||||||
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Pre-assignment
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Screening details |
A total of 12 participants 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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Cerezyme | ||||||
Arm description |
Participants received Cerezyme 60 U/kg by IV infusion once every 2 weeks for 12 months. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Cerezyme
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Investigational medicinal product code |
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Other name |
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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 |
Cerezyme 60 U/kg was administered by IV infusion once every 2 weeks for 12 months.
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Baseline characteristics reporting groups
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Reporting group title |
Cerezyme
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Reporting group description |
Participants received Cerezyme 60 U/kg by IV infusion once every 2 weeks for 12 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cerezyme
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Reporting group description |
Participants received Cerezyme 60 U/kg by IV infusion once every 2 weeks for 12 months. | ||
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End point title |
Mean Change From Baseline in Hemoglobin at Month 12 [1] | ||||||||
End point description |
The mean change in hemoglobin from baseline to Month 12 was assessed. Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed.
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End point type |
Primary
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End point timeframe |
Baseline and Month 12
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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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change From Baseline in Platelet Count at Month 12 [2] | ||||||||
End point description |
The mean change in platelet count from baseline to Month 12 was assessed. Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed.
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End point type |
Primary
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End point timeframe |
Baseline and Month 12
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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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [3] | ||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the adverse events that occurred between the first dose of study drug and the end of the study. Serious adverse events (SAE): Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Safety population included all participants 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 of study treatment (Day 1) up to Day 30 post last dose of study treatment, approximately 13 months
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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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Change From Baseline in Liver and Spleen Volume at Month 12 | ||||||||||||
End point description |
Magnetic resonance imaging (MRI) was used for volumetric measurement of liver and spleen. The mean change in liver and spleen volumes from baseline to Month 12 was assessed. Negative value signifies reduction of volume. Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed. Here ’n’= number of participants with available data for a particular category.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Frequency of Bone Pain at Month 12 | ||||||||
End point description |
The frequency of bone pain was assessed at baseline and up to end of study. All participants were asked the following question: ‘What is the frequency of your bone pain during last month?’. For bone pain occurring after walking or related to exertion, frequency of bone pain was classified as "pain on exertion or exertion"; for intermittent, irregular and occasional bone pain, frequency of bone pain was categorized as "intermittent or irregular pain"; for persistent pain, frequency of bone pain was defined as 30 times/month. Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Duration of Bone Pain at Month 12 | ||||||||
End point description |
The duration of bone pain was assessed at baseline and up to end of study. All participants were asked the following question: ‘How long did single bone pain attack last?’. For bone pain occurring after walking or related to exertion, duration of bone pain was classified as "pain on exertion or exertion"; for intermittent, irregular and occasional bone pain, duration of bone pain was categorized as "intermittent or irregular pain"; for persistent pain, duration of bone pain was categorized as "persistent bone pain". Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Severity of Bone Pain at Month 12 | ||||||||
End point description |
The severity of bone pain was assessed at baseline and up to end of study. Numeric Rating Scale (NRS) was used to evaluate the severity of bone pain. All participants were asked the following question: ‘How would you rate your bone pain?’. Score range 0-10 was used to represent the level of pain, where higher scores indicate more severe bone pain. Evaluable population included all participants with no critical protocol deviations.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in the Number of Bone Crisis at Month 12 | ||||||||
End point description |
The number of bone crises were recorded at baseline and up to the end of study. Bone crisis was defined as pain with acute onset which required immobilization of the affected area, narcotics for relief of pain and might be accompanied by one or more of the following: periosteal elevation, elevated white blood cell count, fever, or debilitation of >3 days. Evaluable population included all participants with no critical protocol deviations. Only those participants with data available were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Quality of life (QoL) as Assessed by SF-12v2 Health Survey (SF-12v2) at Months 3, 6, 9, and 12 | ||||||||||||||||||||||||
End point description |
The SF-12v2 was used to assess the participant's functional health and well-being. SF-12v2 transformed health domain scale total raw scores to 0–100 scores, where higher score means better level of physical and mental health. Evaluable population included all participants with no critical protocol deviations. Only adult participants were included for the analysis of this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline and Months 3, 6, 9, and 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in QoL as Assessed by Measurement Model for the Pediatric Quality of Life Inventory (PedsQL) at Months 3, 6, 9, and 12 | ||||||||||||||||||||||||
End point description |
The PedsQL was used to assess health-related quality of life in children. For the young child (aged 7 and below), the PedsQL was administered by their parents. Children aged 8-18 self-administered the PedsQL. Participants reported their function using a 5-point Likert scale ranging from 0 to 4. The responses were reverse scored and linearly transformed to a 0 to 100 scale, with a higher score indicating a higher QOL in pediatrics. Evaluable population included all participants with no critical protocol deviations. Only pediatric participants were included for the analysis of this endpoint. Here ’n’= number of participants with available data for a particular category.
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End point type |
Secondary
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End point timeframe |
Baseline and Months 3, 6, 9, and 12
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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 |
From first dose of study treatment (Day 1) up to Day 30 post last dose of study treatment, approximately 13 months
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Adverse event reporting additional description |
Safety population included all participants who received at least 1 dose of study intervention.
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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 |
26.1
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Reporting groups
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Reporting group title |
Cerezyme
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Reporting group description |
Participants received Cerezyme 60 U/kg by IV infusion once every 2 weeks for 12 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Jun 2020 |
The amendment of the protocol was mainly based on the communication with Center for Drug Evaluation of National Medical Products Administration of China. The major change was to include Gaucher Disease type Ⅲ Chinese participants instead of Gaucher Disease participants with significant change of electroencephalogram. There were also changes in inclusion and exclusion criteria based on opinions from principal investigators. |
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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 | |||
