Back to resultsAAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease
Primary Purpose
Pompe Disease
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ACTUS-101
Sponsored by
About this trial
This is an interventional treatment trial for Pompe Disease focused on measuring Gene Therapy
Eligibility 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.
Sites / Locations
- Duke University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
A one-time intravenous infusion of ACTUS-101 (dose level 1)
A one-time intravenous infusion of ACTUS-101 (dose level 2)
A one-time intravenous infusion of ACTUS-101 (dose level 3)
Outcomes
Primary Outcome Measures
Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability)
The incidence of patient reported TEAEs will be measured according to protocol specifications.
Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability)
The incidence of patient reported SAEs will be measured according to protocol specifications.
Number of Participants With Abnormal Laboratory Values
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
Muscle GAA Bioactivity
Muscle GAA activity will be compared to baseline by muscle biopsy
Serum GAA Bioactivity
Serum GAA activity will be compared to baseline by blood screening
Glycogen content in muscle
Muscle glycogen level compared to baseline by muscle biopsy
Anti-rhGAA antibody formation
Anti-rhGAA antibodies monitored by ELISA
Muscle Status Testing - 6 minute walk test
The 6-minute walk test will be performed and results compared to baseline.
Muscle Status Testing - Gross Motor Function Measure
The gross motor function measure (GMFM88) will be performed and the results compared to baseline.
Muscle Status Testing - Quick Motor Function Test (QMFT) Measure
Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline.
Muscle Status Testing - Gait, Stairs, Gower, Chair
The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.
Pulmonary Function Testing
Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.
Muscle Status Testing - Timed up and Go (TUG)
Measurement of functional motor abilities using the Timed up and Go (TUG) test will be performed and the results compared with baseline.
Full Information
NCT ID
NCT03533673
First Posted
April 13, 2018
Last Updated
June 27, 2023
Sponsor
Asklepios Biopharmaceutical, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03533673
Brief Title
AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease
Official Title
A Phase 1 Study of the Safety of AAV2/8-LSPhGAA (ACTUS-101) in Late-onset Pompe Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 17, 2018 (Actual)
Primary Completion Date
September 30, 2022 (Actual)
Study Completion Date
March 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Asklepios Biopharmaceutical, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Open-label, ascending dose trial of ACTUS-101 administered intravenously.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease
Keywords
Gene Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
A one-time intravenous infusion of ACTUS-101 (dose level 1)
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
A one-time intravenous infusion of ACTUS-101 (dose level 2)
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
A one-time intravenous infusion of ACTUS-101 (dose level 3)
Intervention Type
Biological
Intervention Name(s)
ACTUS-101
Intervention Description
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.
Primary Outcome Measure Information:
Title
Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability)
Description
The incidence of patient reported TEAEs will be measured according to protocol specifications.
Time Frame
78 weeks
Title
Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability)
Description
The incidence of patient reported SAEs will be measured according to protocol specifications.
Time Frame
78 weeks
Title
Number of Participants With Abnormal Laboratory Values
Description
Laboratory assessments will be performed (CBC, Chemistry, urinalysis, serology, anti-GAA antibody, T-cell response, GAA activity) and compared to baseline values.
Time Frame
78 weeks
Secondary Outcome Measure Information:
Title
Muscle GAA Bioactivity
Description
Muscle GAA activity will be compared to baseline by muscle biopsy
Time Frame
78 weeks
Title
Serum GAA Bioactivity
Description
Serum GAA activity will be compared to baseline by blood screening
Time Frame
78 weeks
Title
Glycogen content in muscle
Description
Muscle glycogen level compared to baseline by muscle biopsy
Time Frame
78 weeks
Title
Anti-rhGAA antibody formation
Description
Anti-rhGAA antibodies monitored by ELISA
Time Frame
78 weeks
Title
Muscle Status Testing - 6 minute walk test
Description
The 6-minute walk test will be performed and results compared to baseline.
Time Frame
78 weeks
Title
Muscle Status Testing - Gross Motor Function Measure
Description
The gross motor function measure (GMFM88) will be performed and the results compared to baseline.
Time Frame
78 weeks
Title
Muscle Status Testing - Quick Motor Function Test (QMFT) Measure
Description
Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline.
Time Frame
78 weeks
Title
Muscle Status Testing - Gait, Stairs, Gower, Chair
Description
The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.
Time Frame
78 weeks
Title
Pulmonary Function Testing
Description
Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.
Time Frame
78 weeks
Title
Muscle Status Testing - Timed up and Go (TUG)
Description
Measurement of functional motor abilities using the Timed up and Go (TUG) test will be performed and the results compared with baseline.
Time Frame
78 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease
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