A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late-Onset Pompe Disease (PROGRESS-GT LOPD)

Official title

A Single-Arm, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability and Efficacy of a Single Intravenous Infusion of AB-1009 in Adult Participants With Late-Onset Pompe Disease (LOPD)

Overview

This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of AB-1009 in adult participants with late-onset Pompe disease (LOPD).

Detailed description

This is an open-label study, up to 12 participants will receive a single IV infusion of AB-1009. Participants will be assigned to either cohort 1 (1.0E13 vg/kg) or Cohort 2 (1.5E13 vg/kg) based on enrollment in the study.

Study duration will include a screening period of up to 75 days, primary observation of 52 weeks, and a long-term follow-up period of 4 years.

Interventions

• Genetic AB-1009 (GAA Gene)
  A single intravenous infusion of AB-1009

Primary outcome measures

• Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the primary observation period [Time frame: Day 1 (Dosing) through Week 52 (the end of the primary observation period)]

Secondary outcome measures (12)

• Area under the curve (AUC) of GAA activity in serum [Time frame: Baseline through Week 52]
• Viral shedding (whole blood, saliva, urine) [Time frame: Day 1 through Week 24 (or until 3 consecutive data points are at or below the limit of detection)]
• AUC of urinary Glc4 [Time frame: Baseline during the primary observation period (through Week 52)]
• Change from baseline in GAA activity in muscle biopsy tissue at Week 52 [Time frame: Baseline and Week 52]
• Change from baseline in muscle biopsy glycogen content at Week 52 [Time frame: Baseline and Week 52]
• Change from baseline in forced vital capacity (FVC) (% predicted) at Week 24 and Week 52 [Time frame: Baseline, Week 24, and Week 52]
• Change from baseline in maximum inspiratory pressure (MIP) at Week 24 and Week 52 [Time frame: Baseline, Week 24, and Week 52]
• Change from baseline in maximum expiratory pressure (MEP) at Week 24 and Week 52 [Time frame: Baseline, Week 24, and Week 52]
• Change from baseline in distance walked in the 6-Minute Walk Test (6MWT) at Week 24 and Week 52 [Time frame: Baseline, Week 24, and Week 52]
• Patient's Global Impression of Change (PGI-C) at Week 24 and Week 52 [Time frame: Week 24 and Week 52]
• Clinical Global Impression of Change (CGI-C) at Week 24 and Week 52 [Time frame: Week 24 and Week 52]
• Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) for physical function changes at Week 24 and Week 52 [Time frame: Baseline, Week 24, and Week 52]

Eligibility criteria

Inclusion criteria

• Participant must be ≥18 to ≤65 years of age at the time of signing the informed consent form.
• Confirmed GAA enzyme deficiency from any tissue source and/or confirmed biallelic GAA gene mutations.
• Undergone enzyme replacement treatment (ERT) (either alglucosidase alfa (Lumizyme®), avalglucosidase alfa-ngpt (Nexviazyme®)), or cipaglucosidase alfa (Pombiliti®) for at least 6 months (at least 10 infusions) before signing the initial informed consent form. During the screening process, participants need to remain on their current ERT until close to dosing;
• FVC in the upright position ≥30% and ≤80% of predicted;
• Capable of walking at least 100 meters in the 6MWT (use of a cane, quad cane, or standard walker is permitted);
• Male or female. Contraceptive/barrier use by men and women requirements as per protocol.
• Capable of giving informed consent.
• Able to understand and comply with all study procedures.

Exclusion criteria

• Severe cardiomyopathy, defined as left ventricular ejection fraction (LVEF) <40% or New York Heart Association (NYHA) functional class 3 or above;
• Require invasive mechanical ventilation, or rely on noninvasive ventilation during the day;
• Intolerance to ERT or investigator-assessed intolerance to ERT, prior experience of serious ERT-related infusion-associated reactions (IARs);
• Have known intrinsic liver diseases, including hepatitis, HIV-related liver disease, prior diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, severe fatty liver, cirrhosis or liver fibrosis ≥stage 2, ultrasound-identified liver neoplasms, or laboratory tests suggesting elevated alpha-fetoprotein. Patients with liver function tests including ALT or AST >3× upper limit of normal (ULN) or any total bilirubin above ULN during screening will also be excluded;
• Prior or ongoing medical condition(s), including any active infection, malignancy within 5 years of screening (except basal or squamous cell skin cancer), physical finding(s), assessment findings, or laboratory abnormality that, in the investigator's opinion, would impact participant's safety and compliance with the study procedures.
• Have received gene therapy prior to screening;
• Have received any systemic immunosuppressants (except inhalation or topical use) other than glucocorticoids 30 days prior to screening through completion of screening through completion of screening, and/or known intolerance to immunosuppressants such as glucocorticoids; other concomitant immunosuppression would require sponsor approval.
• Use of investigational drugs or drugs that could affect this study as evaluated by the investigator within 30 days prior to screening through completion of Week 52 or within 5 half-lives of the investigational drug (whichever is longer);
• Have received any vaccine within 30 days prior to dosing;
• Other conditions that make the participant not eligible for the study according to the investigator.
• Contraindication to MRI, hypersensitivity to contrast dyes, shellfish, or iodine, or implanted spinal rods, cardiac pacemaker, or other implantation that would distort cMRI images.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• Barrow Neurological Institute — Phoenix
• University of California, Irvine (UCI) — Irvine
• Stanford Neuroscience Health Center — Palo Alto
• NYU Langone — New York
• Duke University — Durham
• Hospital of the University of Pennsylvania — Philadelphia
• University of Pittsburgh Medical Center (UPMC) — Pittsburgh
• University of Texas Southwest Medical Center — Dallas
• … and 1 more center

Identifiers

NCT: NCT07282847 · ASK-POM9-CS101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗