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

Pompe Disease Clinical Trial

Official title:

A Phase 1 Study of the Safety of AAV2/8-LSPhGAA (ACTUS-101) in Late-onset Pompe Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03533673
• Other study ID #: ACT-CS101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 17, 2018
• Est. completion date: March 2026

Study information

• Verified date: June 2023
• Source: Asklepios Biopharmaceutical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, ascending dose trial of ACTUS-101 administered intravenously.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7
• Est. completion date: March 2026
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease

Intervention

Biological:
• ACTUS-101
Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Asklepios Biopharmaceutical, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	78 weeks
Primary	Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability)	The incidence of patient reported SAEs will be measured according to protocol specifications.	78 weeks
Primary	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.	78 weeks
Secondary	Muscle GAA Bioactivity	Muscle GAA activity will be compared to baseline by muscle biopsy	78 weeks
Secondary	Serum GAA Bioactivity	Serum GAA activity will be compared to baseline by blood screening	78 weeks
Secondary	Glycogen content in muscle	Muscle glycogen level compared to baseline by muscle biopsy	78 weeks
Secondary	Anti-rhGAA antibody formation	Anti-rhGAA antibodies monitored by ELISA	78 weeks
Secondary	Muscle Status Testing - 6 minute walk test	The 6-minute walk test will be performed and results compared to baseline.	78 weeks
Secondary	Muscle Status Testing - Gross Motor Function Measure	The gross motor function measure (GMFM88) will be performed and the results compared to baseline.	78 weeks
Secondary	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.	78 weeks
Secondary	Muscle Status Testing - Gait, Stairs, Gower, Chair	The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.	78 weeks
Secondary	Pulmonary Function Testing	Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.	78 weeks
Secondary	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.	78 weeks