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AAV2/8-LSPhGAA in Late-Onset Pompe Disease

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ClinicalTrials.gov Identifier: NCT03533673
Recruitment Status : Not yet recruiting
First Posted : May 23, 2018
Last Update Posted : May 23, 2018
Sponsor:
Collaborators:
Duke University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Actus Therapeutics, Inc.

Brief Summary:
Open-label, ascending dose trial of AAV2/8-LSPhGAA administered intravenously.

Condition or disease Intervention/treatment Phase
Pompe Disease Biological: AAV2/8LSPhGAA Phase 1 Phase 2

Detailed Description:
This study will be a prospective, open-label trial designed to objectively assess the safety and bioactivity of AAV2/8-LSPhGAA in subjects diagnosed with Pompe disease, which is caused by a defect in acid α-glucosidase (GAA) gene. AAV2/8-LSPhGAA is intended to enable expression of a functional copy of the GAA gene in subject's hepatocytes.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety of AAV2/8-LSPhGAA in Late-onset Pompe Disease
Estimated Study Start Date : October 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Experimental: Cohort 1
A one-time intravenous infusion of AAV2/8-LSPhGAA (dose level 1)
Biological: AAV2/8LSPhGAA
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.

Experimental: Cohort 2
A one-time intravenous infusion of AAV2/8-LSPhGAA (dose level 2)
Biological: AAV2/8LSPhGAA
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.




Primary Outcome Measures :
  1. Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability) [ Time Frame: 52 weeks ]
    The incidence of patient reported TEAEs will be measured according to protocol specifications.

  2. Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability) [ Time Frame: 52 weeks ]
    The incidence of patient reported SAEs will be measured according to protocol specifications.

  3. Number of Participants With Abnormal Laboratory Values [ Time Frame: 52 weeks ]
    Laboratory assessments will be performed (CBC, Chemistry, urinalysis, serology, anti-GAA antibody, T-cell response, GAA activity) and compared to baseline values.


Secondary Outcome Measures :
  1. Muscle GAA Bioactivity [ Time Frame: 12 weeks ]
    Muscle GAA activity will be compared to baseline by muscle biopsy

  2. Plasma GAA Bioactivity [ Time Frame: 12 weeks ]
    Plasma GAA activity will be compared to baseline by blood screening

  3. Glycogen content in muscle [ Time Frame: 12 weeks ]
    Muscle glycogen level compared to baseline by muscle biopsy

  4. Anti-GAA antibody formation [ Time Frame: 52 weeks ]
    Anti-hGAA antibodies monitored by ELISA

  5. Muscle Status Testing - 6 minute walk test [ Time Frame: 52 weeks ]
    The 6-minute walk test will be performed and results compared to baseline.

  6. Muscle Status Testing - Gross Motor Function Measure [ Time Frame: 52 weeks ]
    The gross motor function measure (GMFM88) will be performed and the results compared to baseline.

  7. Muscle Status Testing - Motor Function Measure [ Time Frame: 52 weeks ]
    Measurement of functional motor abilities using the Motor Function Measure (MFM) test will be performed and the results compared with baseline.

  8. Muscle Status Testing - Gait, Stairs, Gower, Chair [ Time Frame: 52 weeks ]
    The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.

  9. Pulmonary Function Testing [ Time Frame: 52 weeks ]
    Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.

  10. Quality of Life Measures - Fatigue Severity Scale [ Time Frame: 52 weeks ]
    Quality of Life measurements using the Fatigue Severity Scale will be taken and results compared to baseline.

  11. Quality of Life Measures - R-PAct (Rasch-built Pompe specific activity scale) [ Time Frame: 52 weeks ]
    Quality of Life measurements using R-PAct Pompe scale (developed to measure Pompe patients' ability to carry out daily life activities and social participation) will be taken and results compared to baseline.

  12. Quality of Life Measures - NIH PROMIS [ Time Frame: 52 weeks ]
    Quality of Life measurements using the NIH PROMIS (patient reported outcomes measurement information system) tool will be taken and results compared to baseline.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Pompe disease by blood or skin fibroblast GAA assay and GAA gene sequencing,
  • Age: 18+ years at enrollment.
  • Subjects are capable of giving written consent.
  • 6MWT latency <85% of expected.
  • FVC >20% of expected (supine).
  • Receiving ERT at standard dose (20 mg/kg every 2 weeks) for at least 52 weeks, OR not having received ERT for at least 52 weeks.

Exclusion Criteria:

  • ELISA positive for anti-AAV8 capsid IgG antibodies (>1:5)
  • Clinically relevant illness within two weeks of enrollment including fever > 38.2o C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy
  • Chronic heart disease (arrhythmia, cardiomyopathy)
  • Elevated alanine aminotransferase (ALT) > upper limit of normal (ULN)
  • History of seizure disorder
  • History of diabetes
  • Pregnancy
  • Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks
  • History of hypersensitivity to β2-agonist drugs such as albuterol, levalbuterol (Xopenex),bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent), which contraindicates pulmonary function testing.
  • Anti-GAA IgG with titer >1:100,000

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): NCT03533673


Contacts
Contact: Dwight Koeberl, MD, PhD 919-684-2036 dwight.koeberl@duke.edu

Locations
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27705
Contact: Edward Smith, MD         
Principal Investigator: Edward C Smith, MD         
Sponsors and Collaborators
Actus Therapeutics, Inc.
Duke University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Principal Investigator: Edward C Smith, MD Duke University
  Study Documents (Full-Text)

Documents provided by Actus Therapeutics, Inc.:
Informed Consent Form  [PDF] February 16, 2018


Responsible Party: Actus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03533673     History of Changes
Other Study ID Numbers: ACT101
1U01AR071693-01 ( U.S. NIH Grant/Contract )
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glycogen Storage Disease Type II
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases