Gene Transfer Study in Patients With Late Onset Pompe Disease

NCT04174105 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AT845-012019-003595-38
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a phase 1/2 open-label, ascending dose, multicenter clinical study to evaluate the safety and efficacy of AT845 in adult (aged ≥ 18 years) subjects, ambulatory or nonambulatory, with Late Onset Pompe Disease (LOPD).

Conditions

Pompe Disease (Late-onset)

Keywords

LOPD

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability over time

  Frequency of adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

  Up to month 120

• GAA enzymatic activity

  Change from baseline in GAA enzymatic activity in muscle biopsies at week 12

  Baseline and Week 12

• GAA protein expression

  Change from baseline in GAA protein expression in muscle biopsies at week 12.

  Baseline and Week 12

Secondary Outcomes (11)

• Vector Copy Number

  Baseline and Week 12

• Thigh Fat Fraction

  Baseline and Month 18

• 6-Minute Walk Test (for ambulatory patients)

  Baseline, Week 24 and Week 48

• Percentage Predicted for 6-Minute Walk Test (for ambulatory patients)

  Baseline, Week 24 and Week 48

• Forced Vital Capacity (FVC)

  Baseline, Week 24 and Week 48

Study Arms (3)

Initial Dose Cohort

EXPERIMENTAL

3x10\^13 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

Second Dose Cohort

EXPERIMENTAL

6x10\^13 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

Third Dose Cohort

EXPERIMENTAL

1x10\^14 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

Interventions

zocaglusagene nuzaparvovec GENETIC

AT845 is an AAV8 vector delivering a functional copy of the human GAA gene, under the control of a muscle-specific promoter

Also known as: AT845

Initial Dose Cohort; Second Dose Cohort; Third Dose Cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is aged ≥ 18 years.
• Participant has a documented clinical diagnosis of Pompe disease by genetic testing.
• Participant has received enzyme replacement therapy (ERT) with rhGAA for the previous ≥ 2 years.
• Participant has been on a stable standard dose (at least 20 mg/kg every 2 weeks) of ERT with rhGAA for at least the previous 6 months.
• Participant or legally authorized representative(s) (LAR) (if applicable) provides written informed consent.
• Participant and LAR(s) are willing and able to comply with study visits and study procedures.
• Participant must agree to refrain from blood or blood products donation and sperm or egg donation from the time of AT845 administration until the later of 90 days or 3 consecutive negative viral shedding samples
• Participants enrolled in previous protocol versions 1 through 9: Participant has upright FVC ≥ 30% of predicted normal value. Participants enrolled starting with protocol version 10 and subsequent amendments: Participant has upright FVC ≥ 30% and ≤ 85% of predicted normal value.
• Participants enrolled starting with protocol version 10 and subsequent amendments: Participant who is able to ambulate ≥ 40 m without stopping and without the use of an assistive device. The use of an assistive device for community ambulation is acceptable. (Participants enrolled under previous protocol versions 1 through 9 will not be excluded if they do not meet this criterion during Rescreening visit).

You may not qualify if:

• Participant is currently participating in an interventional study or has received gene or cell therapy.
• Participant tests positive for AAV8 antibodies with titers \>1:20 neutralizing.
• Participant has received immune-modulating agents within 90 days before dosing (use of inhaled corticosteroids is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 30 days before dosing. Concomitant medications that may predispose the participant to peripheral neuropathy will be evaluated.
• Participant has any clinically significant laboratory values (other than those directly associated with LOPD \[e.g., GAA, serum creatine kinase (CK)\]) that would preclude participation in the study.
• Participant has serological or viral load evidence of HIV-1 or HIV-2.
• Participant has received drugs for treatment of myopathy or neuropathy with immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab) within 3 months prior to starting the study
• Participant has a high risk for a severe allergic reaction to rhGAA (ie, previous moderate to severe anaphylactic reaction to alglucosidase alfa or and/or a history of sustained high immunoglobulin G \[IgG\] antibody titers to alglucosidase alfa that suggests a high risk for an allergic reaction to ERT).
• Participant has a history of hypersensitivity to β2 agonist drugs such as albuterol, levalbuterol, bitolterol, pirbuterol, terbutaline, salmeterol, which contraindicates pulmonary function testing.
• Participant has an active viral infection based on clinical observation.
• Participant has a history of or concurrent medical condition other than Pompe disease that could jeopardize safety of the participant or impact study results.
• Participant has a history of, or currently has, a clinically important cardiac condition, such as an echocardiogram (ECHO) with ejection fraction below 40% or has symptoms or signs of cardiomyopathy that precludes enrollment.
• Participant has a contraindication to study drug or to corticosteroids, or has demonstrated hypersensitivity to any of the components of the study drug.
• Participant tests positive for GAA antibodies with titers \> 1:50,000 total
• Participant has a history of hypersensitivity to MRI contrast agents including gadolinium.
• Participant has a known hypersensitivity to local anesthetics such as lidocaine.

Sponsors & Collaborators

• Astellas Gene Therapies: lead

Study Sites (4)

University of California Irvine, Department of Neurology

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Utah, Division of Medical Genetics

Salt Lake City, Utah, 84108, United States

Location

Newcastle Upon Tyne Hospitals Foundation Trust Clinical Research Facility

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

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 Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

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

Model Details: Up to 3 nominal dose levels of AT845 are planned to be evaluated in this study. A single AT845 administration via IV infusion is planned for each subject. The initial dosing cohort received a single dose of 3×10\^13 vg/kg. The second dose cohort will receive a single dose of 6×10\^13 vg/kg. The third dose cohort will receive a single dose of 1×10\^14 vg/kg. Dose escalation between cohorts will be based on evaluations of safety and in consultation with the independent DMC.

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 22, 2019
• Study Start: October 27, 2020
• Primary Completion (Estimated): February 28, 2035
• Study Completion (Estimated): February 28, 2035
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (1)