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AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03533673
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : May 31, 2022
Sponsor:
Information provided by (Responsible Party):
Asklepios Biopharmaceutical, Inc.

Study Description
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Brief Summary:
Open-label, ascending dose trial of ACTUS-101 administered intravenously.

Condition or disease Intervention/treatment Phase
Pompe Disease Biological: ACTUS-101 Phase 1 Phase 2

Detailed Description:
This study will be a prospective, open-label trial designed to objectively assess the safety and bioactivity of ACTUS-101 in subjects diagnosed with Pompe disease, which is caused by a defect in acid α-glucosidase (GAA) gene. ACTUS-101 is intended to enable expression of a functional copy of the GAA gene in subject's hepatocytes.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Allocation: Non-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 (ACTUS-101) in Late-onset Pompe Disease
Actual Study Start Date : December 17, 2018
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : April 2028

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
A one-time intravenous infusion of ACTUS-101 (dose level 1)
 Biological: ACTUS-101
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 ACTUS-101 (dose level 2)
 Biological: ACTUS-101
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.
Experimental: Cohort 3
A one-time intravenous infusion of ACTUS-101 (dose level 3)
 Biological: ACTUS-101
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.
Experimental: Cohort 4
A one-time intravenous infusion of ACTUS-101 (comparable to dose level 1)
 Biological: ACTUS-101
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.
Experimental: Cohort 5
A one-time intravenous infusion of ACTUS-101 (comparable to dose level 3)
 Biological: ACTUS-101
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability) [ Time Frame: 78 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: 78 weeks ]
    The incidence of patient reported SAEs will be measured according to protocol specifications.

  3. Number of Participants With Abnormal Laboratory Values [ Time Frame: 78 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: 78 weeks ]
    Muscle GAA activity will be compared to baseline by muscle biopsy

  2. Serum GAA Bioactivity [ Time Frame: 78 weeks ]
    Serum GAA activity will be compared to baseline by blood screening

  3. Glycogen content in muscle [ Time Frame: 78 weeks ]
    Muscle glycogen level compared to baseline by muscle biopsy

  4. Anti-rhGAA antibody formation [ Time Frame: 78 weeks ]
    Anti-rhGAA antibodies monitored by ELISA

  5. Muscle Status Testing - 6 minute walk test [ Time Frame: 78 weeks ]
    The 6-minute walk test will be performed and results compared to baseline.

  6. Muscle Status Testing - Gross Motor Function Measure [ Time Frame: 78 weeks ]
    The gross motor function measure (GMFM88) will be performed and the results compared to baseline.

  7. Muscle Status Testing - Quick Motor Function Test (QMFT) Measure [ Time Frame: 78 weeks ]
    Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline.

  8. Muscle Status Testing - Gait, Stairs, Gower, Chair [ Time Frame: 78 weeks ]
    The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.

  9. Pulmonary Function Testing [ Time Frame: 78 weeks ]
    Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.

  10. Muscle Status Testing - Timed up and Go (TUG) [ Time Frame: 78 weeks ]
    Measurement of functional motor abilities using the Timed up and Go (TUG) test will be performed and the results compared with baseline.


Eligibility Criteria
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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.
  • Subjects with a confirmed diagnosis of LOPD who have been treated with 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.

Exclusion Criteria:

  • Invasive ventilation required or noninvasive ventilation required while awake and upright.
  • FVC <20% of predicted (supine).
  • Received any live vaccination 2 months prior to study Day 1.
  • Pregnant or nursing mothers.
  • Serology consistent with exposure to HIV, or serology consistent with active hepatitis A, B or C infection. Any active liver disease.
  • 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 prior to Study Day 1. Additionally, subjects cannot participate in any other interventional clinical trial throughout the first 78 weeks after receiving ACTUS-101.
Contacts and Locations
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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): NCT03533673


Contacts
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Contact: AskFirst Patient Engagement askfirst@askbio.com

Locations
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United States, Missouri
Washington University in St. Louis Not yet recruiting
Saint Louis, Missouri, United States, 63130
Contact       neuromuscleresearch@wustl.edu   
Principal Investigator: Alan Pestronk, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Principal Investigator: Jaya Ganesh, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Contact: Ming Xu, MD    919-681-1945    mingfen.xu@duke.edu   
Principal Investigator: Edward C Smith, MD         
Sponsors and Collaborators
Asklepios Biopharmaceutical, Inc.
More Information
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Responsible Party: Asklepios Biopharmaceutical, Inc.
ClinicalTrials.gov Identifier: NCT03533673    
Other Study ID Numbers: ACT-CS101
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: May 31, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Asklepios Biopharmaceutical, Inc.:
Gene Therapy
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
 Metabolism, Inborn Errors
Genetic Diseases, Inborn
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases