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Trial record 11 of 103 for:    Pompe Disease

AAV2/8-LSPhGAA in Late-Onset Pompe Disease

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ClinicalTrials.gov Identifier: NCT03533673
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : February 21, 2019
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.

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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
Actual Study Start Date : November 1, 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 two pathogenic variants in the GAA gene,
  • Age: Greater than or equal to 18 years at enrollment.
  • Subjects are capable of giving written informed consent.
  • Able to walk at least 100 meters on the 6MWT (with assistive devices permitted).
  • FVC within the range of 30% to less 90% (inclusive) of predicted in the upright position.
  • Receiving ERT for at least 104 weeks (inclusive) immediately preceding screening and receiving a stable dose of ERT for the 52-week period immediately preceding dosing.

Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after dosing with ACTUS-101.

  1. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to receiving ACTUS-101.
  2. Intrauterine device in place for at least 90 days prior to receiving ACTUS-101.
  3. Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving ACTUS-101.
  4. Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving ACTUS-101). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject.
  5. Surgical sterilization of partner(s) (vasectomy) for > 180 days prior toACTUS-101.
  6. Hormonal contraceptives starting > 90 days prior to receiving ACTUS-101. If hormonal contraceptives are started less than 90 days prior to receiving ACTUS-101, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives

Male subjects:

  1. Must agree to use a condom from Study Day 1 through 6 months after the time of receiving ACTUS-101.
  2. Must agree not to donate sperm for 6 months after the time of receiving ACTUS-101.
  3. Documented evidence of vasectomy in males for 180 days minimum prior to receiving ACTUS-101 is an acceptable form of contraception.
  4. Males who claim abstinence as their method of contraception are allowed provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving ACTUS-101. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject

Exclusion Criteria:

  • ELISA positive for anti-AAV8 capsid IgG antibodies (>1:5).
  • Invasive ventilation required or noninvasive ventilation required while awake and upright.
  • FVC <20% of predicted (supine).
  • Invasive ventilation required or noninvasive ventilation required while awake and upright.
  • 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.
  • Any condition that would interfere with participation in the study as determined by the principal investigator.
  • Received any live vaccination 4 months prior to study Day 1. (Subjects will also be prohibited from receiving any vaccination within the 4-month period after study Day 1).
  • Pregnant or nursing mothers.
  • Anti-rhGAA IgG with sustained titer >1:12,800 for >6 months at time of enrollment.
  • Serology consistent with exposure to HIV, or serology consistent with active hepatitis A, B or C infection. Any active liver disease.
  • GGT > 1.2x ULN adjusted for age and gender.
  • Bilirubin > 1.2x ULN adjusted for age and gender (unless have a history of Dubin Johnson syndrome).
  • Active infection based upon clinical symptoms.
  • Having started respiratory muscle strength training in the last 6 months prior to study day 1 or having discontinued respiratory muscle strength training in the 6-month period preceding study day 1, or having started respiratory strength training greater than 6 months prior to study day 1 and unwilling to continue for the first year of study participation.
  • Received an investigational drug or participated in another interventional study within 90 days of Study Day 1.

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

Locations
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United States, North Carolina
Duke University 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
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Principal Investigator: Edward C Smith, MD Duke University

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Responsible Party: Actus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03533673     History of Changes
Other Study ID Numbers: ACT-CS101
1U01AR071693-01 ( U.S. NIH Grant/Contract )
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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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
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors