Fabry's Disease
Conditions
Brief summary
This Phase 4 study will evaluate the safety and tolerability of Fabrazyme at current approved dose with increases in the infusion rate and reduced infusion volume. This study aims to generate data to provide the guidance on how infusion rate can be safely increased and minimize the burden of the life-long treatment with Fabrazyme.
Detailed description
The total duration will be up to 7 months
Interventions
Pharmaceutical form: Lyophilized powder for reconstitution Route of administration: IV infusion
DRUGAcetaminophen
Tablet or solution; Oral
DRUGDiphenhydramine
Tablet or solution; Oral
DRUGDexamethasone
Tablet or solution; Oral
DRUGMontelukast
Tablet or chewable tablet or oral granules; Oral
DRUGLoratadine
Tablet or chewable tablet; Oral
DRUGCetirizine
Tablet or oral solution; Oral
DRUGFexofenadine
Tablet or oral suspension; Oral
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Participants with confirmed diagnosis of FD who are ≥2 and ≤65 years of age at the time of signing the informed consent form (ICF) or assent, if applicable. * Cohort 1: female participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. * Cohort 2: non-classic male participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. * Cohort 3: classic male participants with body weight ≥30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. * Cohort 4: participants with body weight \<30 kg who have been treated with Fabrazyme for at least 3 months without IARs during the most recent 3 infusions. Women of childbearing potential must use a highly effective method of contraception through the study.
Exclusion criteria
* Female participants who are pregnant or breastfeeding. * History of significant allergic disease or hypersensitivity to Fabrazyme or other medicinal products. * Contraindication to Fabrazyme or any of the premedications or rescue medications (diphenhydramine, loratadine, cetirizine, fexofenadine, acetaminophen, montelukast, dexamethasone). * Any other medical condition considered to make the increased infusion rate not tolerable at the Investigator's discretion. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Shortest Tolerated Infusion Duration From Pre-study Average of Recent 3 Infusions | Up to 16 weeks | Percent reduction was with respect to the shortest tolerated infusion for the participant. The shortest infusion duration tolerated was the actual shortest duration (highest infusion rate) of a completed infusion tolerated by the participant without experiencing a second infusion associated reaction (IAR). The pre-study infusion duration was derived as the average of the duration of 3 most recent infusions the participant received prior to participating to this study. Percent reduction of infusion duration was calculated as: 100 x (average of pre-study infusion duration \[minutes\] - actual shortest infusion duration tolerated \[minutes\]) / average of pre-study infusion duration (minutes). |
| Shortest Actual Tolerated Infusion Duration | Up to 16 weeks | The shortest infusion duration tolerated was the actual shortest duration (highest infusion rate) of a completed infusion tolerated by the participant without experiencing a second IAR. IARs were events recorded as adverse event of special interest (AESI) and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing Any Infusion Associated Reaction | Up to 16 weeks | Number of participants who achieved the shortest planned duration of infusion time without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. |
| Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing a Second Infusion Associated Reaction | Up to 16 weeks | Number of participants who achieved the shortest planned duration of infusion time without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. |
| Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing Any Infusion Associated Reaction | Up to 16 weeks | Number of participants who tolerated the shortest planned duration of infusion time without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. Participants with an initial planned target duration \<90 minutes were considered a responder if they tolerated at least 1 infusion during the study treatment period with actual duration \<90 minutes. |
| Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing a Second Infusion Associated Reaction | Up to 16 weeks | Number of participants who tolerated the shortest planned duration of infusion time without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. Participants with an initial planned target duration \<90 minutes were considered a responder if they tolerated at least 1 infusion during the study treatment period with actual duration \<90 minutes. |
| Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | Up to 16 weeks | Number of participants who tolerated each planned infusion duration without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. The planned duration of infusion time was 120 minutes, 90 minutes, 60 minutes, 40 minutes, and 20 minutes. |
| Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | Up to 16 weeks | Number of participants who tolerated each planned infusion duration without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. The planned duration of infusion time was 120 minutes, 90 minutes, 60 minutes, 40 minutes, and 20 minutes. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 4 centers in United States. A total of 8 participants were screened from 10 November 2023 to 27 August 2024, of which none were screen failures.
Pre-assignment details
A total of 8 participants were enrolled in the study. All participants received same dose in this single-group, single arm study as pre-specified in the protocol and statistical analysis plan (SAP). Note: Reason for not completed = Reason for permanent full study treatment discontinuation.
Participants by arm
| Arm | Count |
|---|---|
| Fabrazyme® All participants received Fabrazyme® 1 mg/kg Q2W via IV infusion for up to 16 weeks (up to 9 infusions). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Fabrazyme® |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 17.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Percent Reduction in Shortest Tolerated Infusion Duration From Pre-study Average of Recent 3 Infusions
Percent reduction was with respect to the shortest tolerated infusion for the participant. The shortest infusion duration tolerated was the actual shortest duration (highest infusion rate) of a completed infusion tolerated by the participant without experiencing a second infusion associated reaction (IAR). The pre-study infusion duration was derived as the average of the duration of 3 most recent infusions the participant received prior to participating to this study. Percent reduction of infusion duration was calculated as: 100 x (average of pre-study infusion duration \[minutes\] - actual shortest infusion duration tolerated \[minutes\]) / average of pre-study infusion duration (minutes).
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fabrazyme® | Percent Reduction in Shortest Tolerated Infusion Duration From Pre-study Average of Recent 3 Infusions | 84.19 percent |
Primary
Shortest Actual Tolerated Infusion Duration
The shortest infusion duration tolerated was the actual shortest duration (highest infusion rate) of a completed infusion tolerated by the participant without experiencing a second IAR. IARs were events recorded as adverse event of special interest (AESI) and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fabrazyme® | Shortest Actual Tolerated Infusion Duration | 20.00 minutes |
Secondary
Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing Any Infusion Associated Reaction
Number of participants who achieved the shortest planned duration of infusion time without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fabrazyme® | Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing Any Infusion Associated Reaction | 8 Participants |
Secondary
Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing a Second Infusion Associated Reaction
Number of participants who achieved the shortest planned duration of infusion time without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fabrazyme® | Number of Participants Who Achieved the Shortest Planned Duration of Infusion Time Without Experiencing a Second Infusion Associated Reaction | 8 Participants |
Secondary
Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction
Number of participants who tolerated each planned infusion duration without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. The planned duration of infusion time was 120 minutes, 90 minutes, 60 minutes, 40 minutes, and 20 minutes.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | 120 minutes | 6 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | 90 minutes | 7 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | 60 minutes | 8 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | 40 minutes | 8 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing Any Infusion Associated Reaction | 20 minutes | 8 Participants |
Secondary
Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction
Number of participants who tolerated each planned infusion duration without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. The planned duration of infusion time was 120 minutes, 90 minutes, 60 minutes, 40 minutes, and 20 minutes.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | 40 minutes | 8 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | 120 minutes | 6 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | 90 minutes | 7 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | 60 minutes | 8 Participants |
| Fabrazyme® | Number of Participants Who Tolerated Each Planned Infusion Duration Without Experiencing a Second Infusion Associated Reaction | 20 minutes | 8 Participants |
Secondary
Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing Any Infusion Associated Reaction
Number of participants who tolerated the shortest planned duration of infusion time without experiencing any IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. Participants with an initial planned target duration \<90 minutes were considered a responder if they tolerated at least 1 infusion during the study treatment period with actual duration \<90 minutes.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fabrazyme® | Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing Any Infusion Associated Reaction | 8 Participants |
Secondary
Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing a Second Infusion Associated Reaction
Number of participants who tolerated the shortest planned duration of infusion time without experiencing a second IAR is reported. ARs were events recorded as AESI and were defined as AEs the Investigator considered related to Fabrazyme® infusion, that occurred on same day as infusion and only after infusion had begun. Participants with an initial planned target duration \<90 minutes were considered a responder if they tolerated at least 1 infusion during the study treatment period with actual duration \<90 minutes.
Time frame: Up to 16 weeks
Population: The ITT analysis set included all participants who were enrolled and allocated to study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fabrazyme® | Number of Participants Who Tolerated Planned Infusion Duration Shorter Than 90 Minutes Without Experiencing a Second Infusion Associated Reaction | 8 Participants |