Niemann-Pick Disease, Type C
Conditions
Keywords
Niemann-Pick Type C1 (NPC1) Disease, neurologic disease, gross motor dysfunction, fine motor dysfunction, dysphagia, swallowing problems, cognitive dysfunction, gait abnormalities, pediatrics
Brief summary
Due to different study designs, the sponsor separated Part C into this separate registration (NCT04958642), leaving Parts A/B in NCT02534844. The trial's final results for the primary outcome measure of Adverse Events (AE) will be reported here. This study is to evaluate how safe and effective adrabetadex is for participants with Niemann-Pick Type C1 (NPC1) disease who experience neurologic symptoms (listed under Keywords). In Parts A/B (NCT02534844), two out of every 3 participants will receive the study drug. The third participant will receive 1 to 2 small needle pricks at the location where the IT injection is normally made (sham control). In Part C, all participants will receive study drug.
Detailed description
Participants in Part C will receive adrabetadex until the investigator considers adrabetadex to no longer be beneficial to the participant, or the development program is discontinued.
Interventions
DRUGAdrabetadex
Mallinckrodt test formulation, administered intrathecal (IT) via lumbar puncture (LP) infusion.
Sponsors
Mandos LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In Part C, all participants receive adrabetadex
Eligibility
Sex/Gender
ALL
Age
4 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
One of the following is required for inclusion into VTS301 Part C: * Has agreed to convert from the monthly dosing regimen used in the NIH phase 1/2a protocol to an every 2 weeks dosing regimen * The investigator has received prior written authorization from the sponsor for the participant to enter VTS301 Part C on an amended dose and/or regimen * Has received prior written authorization from Vtesse to enroll directly into Part C
Exclusion criteria
* None of the inclusion criteria are applicable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to 5 years | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as an AE with onset on or after the start of adrabetadex treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Countries
Australia, France, Germany, New Zealand, Singapore, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
This is an open-label extension phase of study VTS301 (Parts A/B) (NCT02534844). Participants who completed Part B and participants who completed National Institutes of Health (NIH) phase 1 study (Protocol 13-CH-0001) were eligible to participate in this study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Naive Treatment-naive participants received adrabetadex 900 milligrams (mg) administered intrathecal (IT) via lumbar puncture (LP) infusion every 2 weeks until the investigator considered adrabetadex to no longer be beneficial to the participant, or the development program was discontinued. | 18 |
| Previously Treated in Phase I Rollover participants from Study 13-CH-0001 received adrabetadex at an amended dose and/or regimen after prior written authorization from the sponsor. The treatment was continued until the investigator considered adrabetadex to no longer be beneficial to the participant, or the development program was discontinued. | 13 |
| Previously Treated in Part A/B Participants continuing from Part B of the study received adrabetadex 900 mg administered IT via LP infusion every 2 weeks until the investigator considered adrabetadex to no longer be beneficial to the participant, or the development program was discontinued. | 35 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Investigator's Decision | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Termination by Sponsor/Regulatory Authorities | 8 | 4 | 13 |
| Overall Study | Transferred to EAP following study termination | 0 | 0 | 1 |
| Overall Study | Transferred to Expanded Access Program | 1 | 0 | 0 |
| Overall Study | Transferred to OLEX program | 3 | 0 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 9 | 13 |
Baseline characteristics
| Characteristic | Treatment Naive | Previously Treated in Phase I | Previously Treated in Part A/B | Total |
|---|---|---|---|---|
| Age, Continuous | 13.2 years STANDARD_DEVIATION 5.07 | 17.5 years STANDARD_DEVIATION 6.16 | 14.1 years STANDARD_DEVIATION 5.6 | 14.5 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 11 Participants | 29 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 16 Participants | 13 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 20 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 0 / 13 | 1 / 35 |
| other Total, other adverse events | 18 / 18 | 13 / 13 | 34 / 35 |
| serious Total, serious adverse events | 9 / 18 | 7 / 13 | 20 / 35 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as an AE with onset on or after the start of adrabetadex treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to 5 years
Population: The Open-label population included participants who received at least 1 dose of adrabetadex during Part C.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Naive | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 18 Participants |
| Treatment Naive | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| Previously Treated in Phase I | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 13 Participants |
| Previously Treated in Phase I | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 7 Participants |
| Previously Treated in Part A/B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAEs | 34 Participants |
| Previously Treated in Part A/B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 20 Participants |