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

• ClinicalTrials.gov Identifier: NCT03533673
• Recruitment Status: Active, not recruiting
• First Posted: May 23, 2018
• Last Update Posted: June 28, 2023
• Sponsor: Asklepios Biopharmaceutical, Inc.
• Information provided by (Responsible Party): Asklepios Biopharmaceutical, Inc.

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 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
• Actual Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: March 2026

Arms and Interventions

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.

Outcome Measures

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

• 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

Locations

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Asklepios Biopharmaceutical, Inc.

More Information

• Responsible Party: Asklepios Biopharmaceutical, Inc.
• ClinicalTrials.gov Identifier: NCT03533673
• Other Study ID Numbers: ACT-CS101
• First Posted: May 23, 2018
• Last Update Posted: June 28, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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