Niemann-Pick Disease, Type CPhase 2/3NCT03879655
Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1
A Phase 2/3 study testing VTS-270 in people with Niemann-Pick Disease, Type C, run by Mandos LLC at 1 site in Costa Rica.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 4 to 21 years
- Conditions the study is for
- Niemann-Pick Disease, Type C
- What is being tested?
- VTS-270
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteCosta Rica
- Study dates
- 2 Dec 2019to 18 Oct 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be eligible to participate in the study, at the Baseline Visit (except as noted below):
- 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.
- Participant, in the opinion of the Principal Investigator, should continue treatment with VTS-270.
- 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.
- 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.
Who cannot join
- A participant is ineligible for study participation if, at the Baseline Visit:
- Participants discontinued from Study VTS301 for AEs.
- Participant has an unresolved serious adverse event (SAE) for which treatment with VTS-270 has been halted.
- Female participants who are pregnant or nursing.
- Participants with suspected infection of the central nervous system or any systemic infection.
- Participants with a spinal deformity that could impact the ability to perform a LP.
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- Participants with a skin infection in the lumbar region within 2 months of study entry.
- Any of the following laboratory abnormalities at the Baseline Visit:
- Neutropenia, defined as an absolute neutrophil count of less than 1.5 × 10^9/liter (L).
- Thrombocytopenia (platelet count of less than 75 × 10^9/L).
- 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.
- Aspartate aminotransferase or alanine aminotransferase (ALT) greater than 4 × ULN.
- Anemia: hemoglobin greater than 2 standard deviations below normal for age and gender.
- 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.
- Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
- Recent use of anticoagulants (in past 2 weeks prior to first dose [Study Day 0]).
- Active pulmonary disease, oxygen requirement, or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2B/3 Open-label Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 Disease Previously Treated Under Protocol VTS301
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.
Read the detailed description
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.
- Conditions
- Niemann-Pick Disease, Type C
- Being tested
- VTS-270
- Keywords
- Niemann-Pick, NPC
- Medical subject headings
- Niemann-Pick Disease, Type C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VTS-270Drug
Also called 2-hydroxypropyl-β-cyclodextrin, Cyclodextrin, Adrabetadex
Administered IT via LP infusion of VTS-270
| Study group | Role | What they receive |
|---|---|---|
| VTS-270 | Experimental | 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 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. Receives: Drug: VTS-270 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to Week 156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start2 Dec 2019
- Primary completion18 Oct 2021
- Study completion18 Oct 2021
Why it stopped: Terminated by previous Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Niemann-Pick Disease, Type CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mandos LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Lead, Study director, Mandos LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03879655
- Sponsor's protocol ID
- VTS-270-302
- Status last verified
- Dec 2023
- First submitted
- 12 Dec 2018
- Last updated
- 26 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2B/3 Open-label Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 Disease Previously Treated Under Protocol VTS301
- ClinicalTrials.gov ID
- NCT03879655
- Acronym / sponsor ID
- VTS-270-302
- Conditions
- Niemann-Pick Disease, Type C
- Keywords
- Niemann-Pick, NPC
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by previous Sponsor decision
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Mandos LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2019 (actual)
- Primary completion
- 18 Oct 2021 (actual)
- Study completion
- 18 Oct 2021 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Posted 26 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VTS-270 | Experimental | Drug: VTS-270Eligible participants who transition into this study will receive treatment with VTS-270 at the last dose level administered in Study VTS301, administered IT via 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. |
Who may qualify
- Ages
- 4 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- To be eligible to participate in the study, at the Baseline Visit (except as noted below):
- 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.
- Participant, in the opinion of the Principal Investigator, should continue treatment with VTS-270.
- 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.
- 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 (18 listed)
- Participants discontinued from Study VTS301 for AEs.
- Participant has an unresolved serious adverse event (SAE) for which treatment with VTS-270 has been halted.
- Female participants who are pregnant or nursing.
- Participants with suspected infection of the central nervous system or any systemic infection.
- Participants with a spinal deformity that could impact the ability to perform a LP.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VTS-270Also: 2-hydroxypropyl-β-cyclodextrin, Cyclodextrin, AdrabetadexAdministered IT via LP infusion of VTS-270 | Drug | VTS-270 |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 156
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Study Lead study director
Mandos LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing VTS-270 in people with Niemann-Pick Disease, Type C, run by Mandos LLC at 1 site in Costa Rica.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Costa Rica. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to Week 156). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2023.