Prediction
**Amended Eligibility Criteria (Version 17):**
Inclusion Criteria:
- To be included in the study, a participant must meet the following criteria:
- Male or female and at least 4 years of age at time of screening.
- Has a confirmed diagnosis of NPC and exhibits neurologic symptoms.
- Patient or parent/guardian must provide written informed consent/assent to participate.
- Has the ability to undergo lumbar puncture (LP) and intra-thecal (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 there is a history of seizures, the condition must be adequately controlled, i.e., the pattern of seizure activity must be stable and the subject must be on a stable dose and regimen of antiepileptic medication during the 1 month prior to Screening, with no change in dose or regimen up to and including the day of the first dose of adrabetadex (Day 1).
- If not currently receiving adrabetadex, agrees to discontinue any other investigational treatments for at least 1 month prior to first dose of adrabetadex (Day 1); subjects who are currently receiving intrathecal adrabetadex are eligible to participate.
- Sexually active females and males must use a medically acceptable method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
Acceptable methods of contraception include barrier method with spermicide, intrauterine device, steroidal contraceptive in conjunction with a barrier method, abstinence, or same-sex partner.
- Patient or parent/guardian must possess the ability, in the clinician’s opinion, to understand and comply with study requirements, including clinical outcome measurements and instructions, for the entire duration of the study.
- Caregiver, parent, guardian, or responsible adult must be able and willing to accompany the subject to study visits.
Exclusion Criteria:
- Weighs less than 15 kg.
- Has uncontrolled psychosis.
- 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 a female who is pregnant or nursing.
- Has a suspected infection of the central nervous system (CNS) or any systemic infection.
- Has a spinal deformity that, in the opinion of the clinician, is likely to impact the ability to perform repeated LPs.
- In the opinion of the clinician, has a serious skin infection in the lumbar region within 2 months of entry into the study.
- Has neutropenia, defined as an absolute neutrophil count of less than 1.0 × 10^9/L.
- Has thrombocytopenia (platelet count less than 75 × 10^9/L).
- Has an activated partial thromboplastin time (aPTT) or prothrombin time (PT) prolonged by greater than 1.5 times the upper limit of normal (ULN) or a known history of a bleeding disorder.
- Has evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
- Has recently used anticoagulants (in the 2 weeks prior to first dose of adrabetadex [Day 1]).
- In the opinion of the clinician, is unable to comply with the protocol or has a medical condition (e.g., cardiovascular, respiratory, hematologic, neurologic, renal) that would potentially increase the risk of participation.
After 21 June 2021, subjects must be discontinued from the study if the investigator does not consider them to be benefiting from treatment with intrathecal adrabetadex and/or they do not understand the risks associated with adrabetadex, including hearing loss.
This discussion with the subject should be documented in the subject’s medical record, and only those subjects (or legally authorized representatives) who have demonstrated an understanding of the risk/benefit of adrabetadex treatment should be permitted to continue in the study.