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

NCT03533673 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ACT-CS101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pompe Disease

Keywords

Gene Therapy

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (10)

• Muscle GAA Bioactivity

  78 weeks

• Serum GAA Bioactivity

  78 weeks

• Glycogen content in muscle

  78 weeks

• Anti-rhGAA antibody formation

  78 weeks

• Muscle Status Testing - 6 minute walk test

  78 weeks

Study Arms (3)

Cohort 1

EXPERIMENTAL

A one-time intravenous infusion of ACTUS-101 (dose level 1)

Genetic: ACTUS-101

Cohort 2

EXPERIMENTAL

A one-time intravenous infusion of ACTUS-101 (dose level 2)

Genetic: ACTUS-101

Cohort 3

EXPERIMENTAL

A one-time intravenous infusion of ACTUS-101 (dose level 3)

Genetic: ACTUS-101

Interventions

ACTUS-101 GENETIC

Adeno-associated virus serotype 8 carrying the human GAA gene under the control of the LSP promoter.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AskBio Inc: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27705, United States

Location

Related Publications (1)

• Smith EC, Hopkins S, Case LE, Xu M, Walters C, Dearmey S, Han SO, Spears TG, Chichester JA, Bossen EH, Hornik CP, Cohen JL, Bali D, Kishnani PS, Koeberl DD. Phase I study of liver depot gene therapy in late-onset Pompe disease. Mol Ther. 2023 Jul 5;31(7):1994-2004. doi: 10.1016/j.ymthe.2023.02.014. Epub 2023 Feb 18.

  PMID: 36805083 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 23, 2018
• Study Start: December 17, 2018
• Primary Completion: September 30, 2022
• Study Completion: March 12, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)