- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03879655
Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1
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
Study Overview
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
-
San José, Costa Rica, 10101
- Hospital Clínica Biblica
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
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:
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: VTS-270
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.
|
Administered IT via LP infusion of VTS-270
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline up to Week 156
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Clinical Study Lead, Mandos LLC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Lymphatic Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Dementia
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Frontotemporal Lobar Degeneration
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Frontotemporal Dementia
- Pick Disease of the Brain
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
- Neurologic Manifestations
Other Study ID Numbers
- VTS-270-302
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Niemann-Pick Disease, Type C
-
National Eye Institute (NEI)CompletedNiemann Pick DiseasesUnited States, United Kingdom
-
Mandos LLCTerminatedNiemann-Pick Type C DiseaseUnited States
-
ActelionCompleted
-
Cyclo Therapeutics, Inc.RecruitingNiemann-Pick Disease, Type C1United States, Spain, Israel, Taiwan, Brazil, Germany, Australia, Poland, Turkey, Italy, United Kingdom
-
Xinhua Hospital, Shanghai Jiao Tong University...UnknownNiemann-Pick Disease, Type C1China
-
Eunice Kennedy Shriver National Institute of Child...RecruitingNiemann-Pick Disease Type C1 | Juvenile Neuronal Ceroid Lipofuscinosis | Smith-Lemli-Opitz Syndrome | Creatine Transporter DeficiencyUnited States
-
Eunice Kennedy Shriver National Institute of Child...TerminatedNiemann-Pick Disease, Type C1United States
-
Cyclo Therapeutics, Inc.CompletedNiemann-Pick Disease, Type C1Israel, Sweden, United Kingdom
-
Vtesse, LLC, a Mallinckrodt Pharmaceuticals CompanyCompletedNiemann-Pick Disease, Type C1United States
-
Cyclo Therapeutics, Inc.Active, not recruitingNiemann-Pick Disease, Type C1United States
Clinical Trials on VTS-270
-
Vtesse, LLC, a Mallinckrodt Pharmaceuticals CompanyWithdrawnNiemann-Pick Disease, Type C
-
Mandos LLCTerminatedNiemann-Pick Type C DiseaseUnited States
-
Eunice Kennedy Shriver National Institute of Child...TerminatedNiemann-Pick Disease, Type C1United States
-
Mandos LLCTerminatedNiemann-Pick Disease, Type CUnited States, Australia, United Kingdom, Turkey, Switzerland, Germany, New Zealand, Singapore, France
-
Vtesse, LLC, a Mallinckrodt Pharmaceuticals CompanyCompletedNiemann-Pick Disease, Type C1United States
-
Mandos LLCCompletedNiemann-Pick Disease, Type CUnited States, Australia, United Kingdom, Germany, France, New Zealand, Singapore, Spain, Turkey
-
Washington University School of MedicineEunice Kennedy Shriver National Institute of Child Health and Human Development...RecruitingNiemann-Pick Disease, Type CUnited States
-
AxeroVision, Inc.CompletedMeibomian Gland Dysfunction | Posterior BlepharitisUnited States
-
Helen S. Driver, PhDBraebon Medical Corporation; National Research Council, CanadaCompleted
-
University of MinnesotaNot yet recruitingAdductor Spasmodic Dysphonia | Laryngeal Dystonia | Abductor Spastic DysphoniaUnited States