Niemann-Pick Type C Disease
Conditions
Keywords
Niemann-Pick, NPC, NPC Type 1 (NPC1)
Brief summary
This study was amended from expanded access to a clinical trial. Information will be collected about long-term safety and effectiveness of adrabetadex shots in the spine every 2 weeks. Participants who were already taking adrabetadex will receive their stable dose. Participants who have not ever taken it will start by receiving 400 mg. Participants will receive treatment every 2 weeks until their doctor finds it does not help them anymore, they withdraw, or the study is stopped for any reason. Participants will not receive additional study treatment after their participation in this protocol.
Interventions
DRUGAdrabetadex
Administered via lumbar puncture (LP) and IT infusion
Sponsors
Mandos LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Continued treatment for children at least 4 years of age
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in the study, a participant must meet the following criteria: * Is male or female and at least 4 years of age at time of screening. * Has a confirmed diagnosis of NPC and exhibits neurologic symptoms. * Has written informed consent/assent to participate. * Has the ability to undergo LP and IT drug administration. * If taking miglustat (Zavesca®), must have been on a stable dose for the past 6 weeks and be willing to remain on a stable dose for the duration of participation in the study, or discontinue miglustat use at least 6 weeks before entry into the study (Day 1). * If has a history of seizures, the condition is adequately controlled as per protocol requirements. * Agrees to discontinue any investigational treatments (other than adrabetadex) for at least 1 month before first dose on Day 1. * If engaging in heterosexual sex, agrees to use a protocol-defined method of contraception throughout the study, and until 30 days after completing the study. * Has a responsible adult who the investigator determines is able and willing to comply with study requirements and a parent/guardian who will accompany the participant to study visits.
Exclusion criteria
Participants will be excluded from the study if they meet any of the following criteria: * Weighs less than 15 kg. * Has a history of hypersensitivity reactions to any product containing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) or has a history of hypersensitivity reactions or allergy to anesthesia/sedation. * Has received treatment with any investigational product (other than adrabetadex) within 1 month prior to Day 1 of treatment. * Is pregnant or nursing. * Has systemic infection or uncontrolled psychosis. * Has known history of a bleeding disorder. * Has used anticoagulants within 2 months of entry into the study. * Per protocol, or in the opinion of the investigator: 1. has laboratory values that would preclude participation 2. has suspected infection of the central nervous system (CNS) 3. has a spinal deformity that could impact performance of repeated LPs 4. has a serious skin infection in the lumbar region or evidence of obstructive or normal pressure hydrocephalus 5. is unable to comply with the study requirements 6. has a medical condition that might increase the risk of participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to Week 134 | An adverse event (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
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Naive Treatment-naive participants received prescribed adrabetadex by IT injection via LP every 2 weeks. Treatment with adrabetadex continued until the clinician considered adrabetadex to be no longer beneficial to the participant, the participant withdrew from the study, adrabetadex received marketing authorization in the United States, or the development program was discontinued. | 9 |
| Previously Treated Previously-treated participants received prescribed adrabetadex by IT injection via LP every 2 weeks. Treatment with adrabetadex continued until the clinician considered adrabetadex to be no longer beneficial to the participant, the participant withdrew from the study, adrabetadex received marketing authorization in the United States, or the development program was discontinued. | 18 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Other than specified | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 2 | 10 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Previously Treated | Total | Treatment Naive |
|---|---|---|---|
| Age, Continuous | 17.94 years STANDARD_DEVIATION 13.705 | 16.07 years STANDARD_DEVIATION 12.388 | 12.33 years STANDARD_DEVIATION 8.718 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 26 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 17 Participants | 24 Participants | 7 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 18 |
| other Total, other adverse events | 9 / 9 | 17 / 18 |
| serious Total, serious adverse events | 5 / 9 | 9 / 18 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (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 Week 134
Population: All enrolled participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Naive | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | All TEAEs | 9 Participants |
| Treatment Naive | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
| Previously Treated | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| Previously Treated | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | All TEAEs | 17 Participants |