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

Phase 1

Active, not recruiting

• Conditions: Pompe Disease
• Interventions: Biological: ACTUS-101

• Registration Number: NCT03533673
• Lead Sponsor: Asklepios Biopharmaceutical, Inc.

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.

Study Timeline

• Study First Submitted: 2018-04-13
• Study First Submitted QC: 2018-05-21
• Study First Posted: 2018-05-23
• Study Start: 2018-12-17
• Primary Completion: 2022-09-30
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-27
• Last Update Posted: 2023-06-28
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 7

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3	ACTUS-101	A one-time intravenous infusion of ACTUS-101 (dose level 3)
Cohort 2	ACTUS-101	A one-time intravenous infusion of ACTUS-101 (dose level 2)
Cohort 1	ACTUS-101	A one-time intravenous infusion of ACTUS-101 (dose level 1)

Primary Outcome Measures

Name	Time	Method
Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability)	78 weeks	The incidence of patient reported SAEs will be measured according to protocol specifications.
Number of Participants With Abnormal Laboratory Values	78 weeks	Laboratory assessments will be performed (CBC, Chemistry, urinalysis, serology, anti-GAA antibody, T-cell response, GAA activity) and compared to baseline values.
Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability)	78 weeks	The incidence of patient reported TEAEs will be measured according to protocol specifications.

Secondary Outcome Measures

Name	Time	Method
Muscle Status Testing - Quick Motor Function Test (QMFT) Measure	78 weeks	Measurement of functional motor abilities using the Quick Motor Function Test (QMFT) will be performed and the results compared with baseline.
Anti-rhGAA antibody formation	78 weeks	Anti-rhGAA antibodies monitored by ELISA
Serum GAA Bioactivity	78 weeks	Serum GAA activity will be compared to baseline by blood screening
Muscle Status Testing - Gross Motor Function Measure	78 weeks	The gross motor function measure (GMFM88) will be performed and the results compared to baseline.
Muscle Status Testing - Timed up and Go (TUG)	78 weeks	Measurement of functional motor abilities using the Timed up and Go (TUG) test will be performed and the results compared with baseline.
Muscle Status Testing - 6 minute walk test	78 weeks	The 6-minute walk test will be performed and results compared to baseline.
Muscle Status Testing - Gait, Stairs, Gower, Chair	78 weeks	The Gait, Stairs, Gower, Chair (GSGC) test will be performed and results compared to baseline.
Muscle GAA Bioactivity	78 weeks	Muscle GAA activity will be compared to baseline by muscle biopsy
Glycogen content in muscle	78 weeks	Muscle glycogen level compared to baseline by muscle biopsy
Pulmonary Function Testing	78 weeks	Pulmonary function (forced vital capacity, FVC in liters of air) measured by spirometer in comparison to baseline.

Trial Locations

Locations (1)

Duke University; 🇺🇸 Durham, North Carolina, United States