Trial of VTS-270 (2-hydroxypropyl-?-cyclodextrin) in Subjects with Niemann-Pick Type C1 Disease

Phase 1

• Conditions: eurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-002548-15-ES
• Lead Sponsor: Vtesse, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-13
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

1. Male or female subjects, ages 6 to 21 years of age at time of screening with onset of neurological symptoms prior to 15 years of age.
2. Diagnosis of NPC1 determined by one of the following:
a. Two NPC1 mutations;
b. Positive filipin staining or oxysterol testing and at least one NPC1 mutation;
c. Vertical supranuclear gaze palsy (VSNGP) in combination with either:
i. One NPC1 mutation, or
ii. Positive filipin staining or oxysterol levels consistent with NPC1 disease and no NPC2 mutations.
3. Subject 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.
4. Ability to undergo a LP and IT drug administration under monitored anesthesia care (conscious sedation) or if medically necessary, general anesthesia.
5. An NPC Clinical Severity Score of 1 through 4, inclusive, in two or more of the following NPC components on the NPC Clinical Severity Scale: ambulation, fine motor skills, or swallowing and a score of 0 through 4 on the cognition component.
6. Total NPC Clinical Severity Score of 10 or greater.
7. If taking miglustat, must have been on a stable dose for past 6 months and be willing to remain on a stable dose for the duration of participation in Parts A and B of the study.
8. Agree to discontinue all non-prescription supplements such as Coenzyme Q10, curcumin, cinnamon, fish oil supplements, high dose vitamin D (>500 mIU/day), N-acetylcystine, acetylleucine, or gingko biloba at least 1 month prior to first dose (Study Day 0). Note: daily administration of an age-appropriate multivitamin is allowed.
9. Agree to discontinue any other investigational treatments for NPC including, for example, vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0).
10. Females of child-bearing 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 (IUD) or steroidal contraceptive in conjunction with a barrier method, or abstinence.
11. Subject or caregiver must possess the ability, per the Investigator, to understand and comply with protocol requirements including clinical outcome measurements and instructions for the entire duration of the study.
12. Caregiver, parent, guardian or responsible adult must be able and willing to accompany the subject to study visits.

Part C
1. Subject has completed Part B, or meets the criteria for the Rescue Option
OR
2. Subject is a current participant in the NIH Phase 1 open-label study and
a. Subject agrees to convert from the dose of VTS-270 currently receiving as a subject in the NIH Phase 1 protocol to the dose chosen for Parts B and C of this study; subjects entering Part C prior to dose selection will receive 900 mg every 2 weeks until the Part B and Part C dose is selected, then will switch to the selected dose
b. Subject agrees to convert from the monthly dosing regimen used in the NIH Phase 1 protocol to an every 2 week dosing regimen.
3. Subject 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 35
F

Exclusion Criteria

1. Exclusion criteria as assessed by NPC Clinical Severity Scale:
a. Unable to walk, wheelchair dependent (ambulation NPC Clinical Severity Score=5)
b. Needs a nasogastric tube or gastric tube for all feedings (swallowing NPC Clinical Severity Score=5)
c. Severe dysmetria (fine motor NPC Clinical Severity Score=5)
d. Minimal cognitive function (cognition NPC Clinical Severity Score=5)
2. Body weight < 15 kg.
3. Prior treatment at any time with HP-?-CD for NPC1 disease. Note: Treatment of other medical conditions with drug preparations containing HP-?-CD as an excipient (inactive ingredient) is acceptable and will not exclude a subject from this trial.
4. Uncontrolled seizures, specifically: greater than 1 seizure over a 2-month period (quantified over the 6 months prior to enrollment), subjects requiring antiepileptic medication changes (other than dose adjustment for weight) in the 6 months prior to screening.
5. Subjects requiring more than 2 antiepileptic medications to control seizures.
6. Subjects on typical or atypical antipsychotics for treatment of psychosis.
7. History of hypersensitivity reactions to any product containing HP-?-CD.
8. Prior treatment with any other investigational product within 3 months prior to first dose (Study Day 0).
9. Female subjects who are pregnant or nursing.
10. Subjects with suspected infection of the CNS or any systemic infection.
11. Spinal deformity that could impact the ability to perform a lumbar puncture.
12. Skin infection in the lumbar region within 2 months of study entry.
13. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 109/L.
14. Thrombocytopenia (platelet count of less than 75 X 109/L).
15. aPTT or PT prolonged by > 1.5 times the upper limit of normal (ULN) or known history of a bleeding disorder.
16. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
17. Recent use of anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
18. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 4 times the ULN.
19. Anemia: Hemoglobin more than 2 standard deviations below normal for age and gender.
20. Estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73m2 calculated using the modified Schwartz formula (2009) for subjects age 6-17 years old or using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) formula for subjects 18 years and older.
21. Active pulmonary disease, oxygen requirement, or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
22. Subjects 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.
23. Life expectancy less than one year.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified