LOPD, Pompe Disease (Late-onset), Pompe Disease Late-Onset
Conditions
Keywords
Pompe Disease, Glycogen Storage Disease, Lysosomal Storage Diseases, Acid Maltase Deficiency, Acid Maltase Deficiency Disease, Gene Therapy, AB-1009, Neuromuscular Disease, LOPD, GAA gene, Adeno-Associated Virus (AAV), Late-Onset Pompe Disease, Acid Alpha-Glucosidase (GAA)
Brief summary
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
GENETICAB-1009 (GAA Gene)
A single intravenous infusion of AB-1009
Sponsors
AskBio Inc
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be ≥18 to ≤65 years of age at the time of signing the informed consent form. 2. Confirmed GAA enzyme deficiency from any tissue source and/or confirmed biallelic GAA gene mutations. 3. 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; 4. FVC in the upright position ≥30% and ≤80% of predicted; 5. Capable of walking at least 100 meters in the 6MWT (use of a cane, quad cane, or standard walker is permitted); 6. Male or female. Contraceptive/barrier use by men and women requirements as per protocol. 7. Capable of giving informed consent. 8. Able to understand and comply with all study procedures.
Exclusion criteria
1. Severe cardiomyopathy, defined as left ventricular ejection fraction (LVEF) \<40% or New York Heart Association (NYHA) functional class 3 or above; 2. Require invasive mechanical ventilation, or rely on noninvasive ventilation during the day; 3. Intolerance to ERT or investigator-assessed intolerance to ERT, prior experience of serious ERT-related infusion-associated reactions (IARs); 4. 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; 5. 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. 6. Have received gene therapy prior to screening; 7. 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. 8. 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); 9. Have received any vaccine within 30 days prior to dosing; 10. Other conditions that make the participant not eligible for the study according to the investigator. 11. Contraindication to MRI, hypersensitivity to contrast dyes, shellfish, or iodine, or implanted spinal rods, cardiac pacemaker, or other implantation that would distort cMRI images.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the primary observation period | Day 1 (Dosing) through Week 52 (the end of the primary observation period) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) of GAA activity in serum | Baseline through Week 52 | — |
| Viral shedding (whole blood, saliva, urine) | Day 1 through Week 24 (or until 3 consecutive data points are at or below the limit of detection) | — |
| AUC of urinary Glc4 | Baseline during the primary observation period (through Week 52) | — |
| Change from baseline in GAA activity in muscle biopsy tissue at Week 52 | Baseline and Week 52 | — |
| Change from baseline in muscle biopsy glycogen content at Week 52 | Baseline and Week 52 | — |
| Change from baseline in forced vital capacity (FVC) (% predicted) at Week 24 and Week 52 | Baseline, Week 24, and Week 52 | — |
| Change from baseline in maximum inspiratory pressure (MIP) at Week 24 and Week 52 | Baseline, Week 24, and Week 52 | — |
| Change from baseline in maximum expiratory pressure (MEP) at Week 24 and Week 52 | 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 | Baseline, Week 24, and Week 52 | — |
| Patient's Global Impression of Change (PGI-C) at Week 24 and Week 52 | Week 24 and Week 52 | Score range: 1-7; lower scores indicate greater improvement and a better outcome. |
| Clinical Global Impression of Change (CGI-C) at Week 24 and Week 52 | Week 24 and Week 52 | Score range: 1-7; lower scores indicate greater improvement and a better outcome |
| Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) for physical function changes at Week 24 and Week 52 | Baseline, Week 24, and Week 52 | PROMIS Short Form v2.0- Physical Function 20a consists of 20 questions that are scored on a scale of 1 to 5. The total score (i.e. sum) ranges between 20 and 100, with a higher score indicating better physical functioning. |
| Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) for fatigue changes at Week 24 and Week 52 | Baseline, Week 24, and Week 52 | PROMIS Short Form v1.0- Fatigue 8a consists of eight questions, scored on a scale of 1 to 5. The total score (i.e. sum) ranges between 8 and 40, with lower scores indicating less fatigue. |
Countries
United States
Contacts
CONTACTAskFirst Patient Engagement
Outcome results
None listed