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Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo(TM) in Pediatric and Adult Patients With Niemann-Pick Disease Type C1 (TransportNPC)

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ClinicalTrials.gov Identifier: NCT04860960
Recruitment Status : Recruiting
First Posted : April 27, 2021
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Cyclo Therapeutics, Inc.

Brief Summary:
A prospective, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 3 and older with confirmed diagnosis of Niemann Pick disease type C1 (NPC1). The objective of this study is to evaluate the safety, tolerability and efficacy of 2000 mg/kg dose of Trappsol Cyclo (hydroxypropyl betacyclodextrin) administered intravenously compared to standard of care. An open-label sub-study in countries following European Medicines Agency (EMA) guidance will enroll asymptomatic or symptomatic patients from infancy up to age 3 to evaluate safety in that population.

Condition or disease Intervention/treatment Phase
Niemann-Pick Disease, Type C1 Drug: Hydroxypropyl-beta-cyclodextrin Drug: Placebo Phase 3

Detailed Description:
The TransportNPC study is a prospective, randomized, double-blind, placebo controlled therapeutic study for 93 patients age 3 and older with confirmed diagnosis of NPC1. The objective of this study is to evaluate the safety, tolerability and efficacy of 2000 mg/kg dose of Trappsol Cyclo (hydroxypropyl betacyclodextrin) administered intravenously by slow infusion every two weeks in addition to standard of care as compared to placebo and standard of care. Standard of care may include Miglustat or leucine products that are not currently under investigation as a therapeutic. Patients will be randomized to receive Trappsol Cyclo or placebo at a 2:1 ratio. The study duration is 96 weeks, with an unblinded interim analysis at 48 weeks. An open-label extension of up to 96 weeks follows the interventional study. Patients whose disease progression worsens by two levels in the Clinical Global Impression of Severity scale over 12 weeks, starting at week 36, may be moved to open label treatment. Efficacy will be measured at week 48 and week 96 by a composite score of major disease features. A sub-study will be conducted in countries following EMA guidance for up to 12 patients age 0 - 3 years who may be asymptomatic. Outcomes for the sub-study are safety, clinical and caregiver impression of disease.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, placebo-controlled, multi-center, double-blind and parallel group study with 2:1 randomization of Trappsol Cyclo plus SOC versus placebo plus SOC over 96 weeks, followed by open-label extension study of 96 weeks
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of 2000mg/kg of Trappsol®Cyclo™ (Hydroxypropyl-B-cyclodextrin) and Standard of Care Compared to Placebo and Standard of Care in Patients With Niemann-Pick Disease Type C1 (TransportNPC)
Actual Study Start Date : July 20, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2025


Arm Intervention/treatment
Experimental: Experimental
Intravenous administration of 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) (based on body weight) diluted with 0.5N saline over at least 6.5 hours every 2 weeks
Drug: Hydroxypropyl-beta-cyclodextrin
Dose is 2000 mg/kg body weight provided every 2 weeks intravenously
Other Name: Trappsol Cyclo

Placebo Comparator: Placebo comparator
Intravenous administration of 0.5N saline over at least 6.5 hours every 2 weeks
Drug: Placebo
0.5N saline provided every 2 weeks intravenously
Other Name: 0.5N saline

Experimental: Open Label sub-study for Infants up to age 3
Up to 12 patients age 0 - 3 yrs in countries following EMA guidance may be enrolled in this open label sub-study. All patients will receive 2000 mg/kg hydroxypropyl betacyclodextrin (Trappsol Cyclo) diluted with 0.5N saline at the clinician's discretion over 6.5 hours every 2 weeks. Outcome measures are safety, clinician and caregiver impressions.
Drug: Hydroxypropyl-beta-cyclodextrin
Dose is 2000 mg/kg body weight provided every 2 weeks intravenously
Other Name: Trappsol Cyclo




Primary Outcome Measures :
  1. Change from Baseline in 4-Domain NPC Severity Score (US only) [ Time Frame: Interim Analysis at Week 48 ]
    Ambulation, Fine Motor, Speech, Swallow

  2. Change from Baseline in 4-Domain NPC Severity Score (US only) [ Time Frame: End of Study at Week 96 ]
    Ambulation, Fine Motor, Speech, Swallow

  3. Change from Baseline in 5-Domain NPC Severity Score (ex-US) [ Time Frame: Interim Analysis at Week 48 ]
    Ambulation, Fine Motor, Speech, Swallow, Cognition

  4. Change from Baseline in 5-Domain NPC Severity Score (ex-US) [ Time Frame: End of Study at Week 96 ]
    Ambulation, Fine Motor, Speech, Swallow, Cognition


Secondary Outcome Measures :
  1. Change in ataxia as measured by Spinocerebellar ataxia functional index [ Time Frame: Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192 ]
    SCAFI

  2. Change in adaptive behavior as measured by Vineland Adaptive Behavior Scale II [ Time Frame: Change from Baseline as measured every 12 weeks through week 96 and end of OLE week 192 ]
    Vineland Adaptive Behavior Scale II

  3. Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale [ Time Frame: Change from Baseline measured at Interim Analysis Week 48 ]
    PAS

  4. Change in Swallow function evaluated by videofluoroscopy or fiberoptic endoscopy and measured by Penetration Aspiration Scale [ Time Frame: Change from Baseline measured at End of Study Week 96 ]
    PAS


Other Outcome Measures:
  1. Change in speaking ability compared to Baseline as measured by voice recordings collected in SpeechVitals mobile device application [ Time Frame: Baseline and every two weeks through week 192 ]
    Measurement of speech features including articulatory precision, speaking and pause rates

  2. Change in speaking ability compared to Pre-Infusion as measured by voice recordings collected in SpeechVitals mobile device application [ Time Frame: Every two weeks through week 192 ]
    Measurement of speech features including articulatory precision, speaking and pause rates within 24 hours post-infusion

  3. Change in Scores of Clinical Global Impression of Severity and of Change compared to Baseline [ Time Frame: Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192 ]
    Clinical Global Impression of Severity and of Change

  4. Change in Scores of Caregiver Global Impression of Severity and of Change scales [ Time Frame: Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192 ]
    Caregiver Global Impression of Severity and of Change

  5. Caregiver Global Impression of Change at 24 hours post infusion [ Time Frame: Baseline and every 2 weeks through week 192 ]
    Caregiver Global Impression of Change at 24 hours post infusion

  6. Change from Baseline in Respiratory function measured by Forced Expiratory Volume in 1 second [ Time Frame: Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 192 ]
    FEV1

  7. Change from Baseline in Liver function as measured by liver enzyme assessments [ Time Frame: Baseline, weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, 96, 100, 120, 144, 168, 192 ]
    Liver function measured by liver enzyme assessments including alanine and aspartate aminotransferases

  8. Safety assessments to include incidence of Adverse Events and Serious Adverse Events [ Time Frame: Regular assessments per protocol through week 192 ]
    Incidence of AEs, SAEs, incidence of abnormal laboratory test results, abnormal ECGs, abnormal physical exams, abnormal vital signs and abnormal hearing assessments assessments



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of NPC1
  2. Annual Severity Increment Score between 0.5 and 2.0 using the 17-domain NPC Severity Scale
  3. Treated or Not Treated with Miglustat (patients must be on a stable dose for at least 3 months prior to the Screening Visit, or have discontinued Miglustat for at least 3 months prior to Screening Visit).
  4. Body weight greater than 4.5 kg and less than or equal to 125 kg
  5. Presenting at least 1 neurological symptom of the disease
  6. Written informed consent
  7. Willing and capable to participate in all aspects of trial design
  8. Ability to travel to the trial site at scheduled times
  9. Contraception requirements per protocol
  10. Caregiver consent as appropriate to participate in all protocol-specified assessments for duration of trial
  11. Inclusion criteria for Open Label Extension are 1) Received double-blind treatment for at least 48 weeks with CGI-S deterioration by at least 2 levels for 2 consecutive assessment visits 12 weeks apart, or 2) completion of double-blind treatment and completed all assessments through week 96, or 3) Discontinued early from double-blind treatment but completed all assessments through week 96
  12. Inclusion criteria for patients age 0 to 3 years in open-label sub-study in countries following EMA guidance only: Confirmed diagnosis of NPC1; treated or not with Miglustat per main study; body weight greater than 4.5kg; patient may be asymptomatic; written assent for child to participate in safety assessments; caregiver consent to participate in caregiver assessments; ability to travel to the trial site for all scheduled visits.

Exclusion Criteria:

  1. Recipient of liver transplant or planned liver transplantation
  2. Patients with active liver disease from any cause other than NPC1
  3. Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or international normalized ratio > 1.8
  4. Stage 3 chronic kidney disease or worse as indicated by an estimated glomerular filtration rate <60ml/min/1.73m2.
  5. Use of curcumin or fish oil within 12 weeks prior to enrollment
  6. Known or suspected allergy or intolerance to the study treatment
  7. In the opinion of the Investigator, the patient's clinical condition does not allow for the blood collection required as per protocol specific procedures.
  8. Treatment with any investigational drug during the 3 months prior to entering the study, including leucine in a clinical trial; however, leucine as a nutraceutical is allowed
  9. Treatment with HPBCD prior to entering the study
  10. Treatment with any other investigational drug during the study
  11. Pregnancy or breastfeeding
  12. Current participation in another trial is not permitted unless it is a noninterventional study and the sole purpose of the trial is for long-term follow up describing clinical features or survival data (registry)
  13. Patients with uncontrolled, severe epileptic seizure periods (at least 3 consecutive severe epileptic seizures that required medication) within 2 months prior to completion of informed consent or assent, as applicable.
  14. Neurologically asymptomatic patients
  15. Inability to participate in the primary study assessment (4D-NPC-SS or 5D-NPC-SS, depending on jurisdiction) as determined by the Investigator
  16. Exclusion criteria for patients age 0 to 3 years in open-label sub-study in countries following EMA guidance only are similar to the main study with the addition of exclusion criterion of history of fetal hydrops or fetal ascites

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04860960


Contacts
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Contact: Lori M Gorski 13864188060 Lori.Gorski@cyclodex.com

Locations
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United States, California
UCSF Benioff Children's Hospital Oakland Not yet recruiting
Oakland, California, United States, 94609
Contact: Cyrus Bascon    510-428-3885    Cyrus.Bascon@ucsf.edu   
Principal Investigator: Caroline Hastings, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Laurie Bailey, MS    513-636-4507    Laurie.Bailey@cchmc.org   
Principal Investigator: Loren Pena, MD PhD         
United States, Pennsylvania
UPMC Children's Hospital Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Nadene Henderson    412-692-3475    Nadene.Henderson@chp.edu   
Principal Investigator: Damara Ortiz, MD         
United States, Virginia
Lysosomal and Rare Disorders Research & Treatment Center, Inc. Recruiting
Fairfax, Virginia, United States, 22030
Contact: Lauren Noll    571-732-4655      
Principal Investigator: Ozlem Goker-Alpan, MD         
Sponsors and Collaborators
Cyclo Therapeutics, Inc.
Investigators
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Study Director: Sharon Hrynkow, PhD Cyclo Therapeutics, Inc.
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Responsible Party: Cyclo Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04860960    
Other Study ID Numbers: CTD-TCNPC-301
First Posted: April 27, 2021    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cyclo Therapeutics, Inc.:
NPC1
cyclodextrin
Additional relevant MeSH terms:
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Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases