Terminated by previous Sponsor decision

This is a multicenter, multinational, open-label study of VTS-270 to evaluate the long-term safety and tolerability of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in participants transitioning from Study VTS301 (Parts A/B [NCT02534844] and Part C [NCT04958642]) with neurologic manifestations of Niemann-Pick Type C1 (NPC1) disease.

Non-clinical studies and a Phase 1 clinical trial suggest that intrathecal (IT) administration of VTS-270 in participants with neurologic manifestations of NPC1 disease has the potential to slow the rate of progression of their neurologic disease. NPC1 disease is a rare, neurodegenerative, inherited, autosomal recessive lysosomal lipid storage disorder primarily in children and teenagers. The disease is characterized by the inability to properly metabolize cholesterol and other lipids within the cell due to mutations in the NPC1 gene causing unesterified cholesterol to accumulate in the brain, liver and spleen.

Eligible participants who transition into this study will receive treatment with VTS-270 at the last dose level administered in Study VTS301, administered IT via lumbar puncture (LP) infusion every 2 weeks, for up to a total duration of 3 years or until the investigator considers VTS-270 to be no longer beneficial to the participant, VTS-270 receives marketing authorization, or the VTS-270 development program is discontinued.

Key Inclusion Criteria:

To be eligible to participate in the study, at the Baseline Visit (except as noted below):

1. Participant completed Part B of Study VTS301 (defined as having completed Visit 27/Week 52 or completed at least through Visit 13/Week 24 and required rescue option) and is continuing in Part C of Study VTS301.
2. Participant, in the opinion of the Principal Investigator, should continue treatment with VTS-270.
3. Females of childbearing potential (not surgically sterile) 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.
4. Participant or parent/guardian must provide written informed consent to participate in the study. In addition to parental consent, assent to participate must also be sought from minor children.

Key Exclusion Criteria:

A participant is ineligible for study participation if, at the Baseline Visit:

1. Participants discontinued from Study VTS301 for AEs.

2. Participant has an unresolved serious adverse event (SAE) for which treatment with VTS-270 has been halted.

3. Female participants who are pregnant or nursing.

4. Participants with suspected infection of the central nervous system or any systemic infection.

5. Participants with a spinal deformity that could impact the ability to perform a LP.

6. Participants with a skin infection in the lumbar region within 2 months of study entry.

7. Any of the following laboratory abnormalities at the Baseline Visit:

   1. Neutropenia, defined as an absolute neutrophil count of less than 1.5 × 10^9/liter (L).
   2. Thrombocytopenia (platelet count of less than 75 × 10^9/L).
   3. Activated partial thromboplastin time or prothrombin time prolonged by greater than 1.5 × the upper limit of normal (ULN) or known history of a bleeding disorder.
   4. Aspartate aminotransferase or alanine aminotransferase (ALT) greater than 4 × ULN.
   5. Anemia: hemoglobin greater than 2 standard deviations below normal for age and gender.
   6. Estimated glomerular filtration rate less than 60 milliliters (mL)/minute/1.73 square meter (m^2) calculated using the modified Schwartz formula (Schwartz et al., 2009) for participants aged 4 through 17 years old or using the Chronic Kidney Disease Epidemiology Collaboration equation formula for participants aged 18 years or older.

8. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.

9. Recent use of anticoagulants (in past 2 weeks prior to first dose [Study Day 0]).

10. Active pulmonary disease, oxygen requirement, or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.

11. Participants who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.

All enrolled participants

Baseline up to Week 156

All enrolled participants

Study was terminated by the Sponsor and only 2 participants were enrolled in the study.