Gene Transfer Study in Patients With Late Onset Pompe Disease


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Trial ID: NCT04174105


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).

Official Title

A Phase 1/2, Open-Label, Ascending-Dose Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT845, an AAV8-Delivered Gene Transfer Therapy in Patients With Late Onset Pompe Disease

Stanford Investigator(s)

John W. Day, MD, PhD
John W. Day, MD, PhD

Professor of Neurology (Adult Neurology), of Pediatrics (Genetics) and, by courtesy, of Pathology


Inclusion Criteria:

   - Subject is aged ≥ 18 years (ambulatory or nonambulatory).

   - Subject has a documented clinical diagnosis of Pompe disease by genetic testing.

   - Subject has received enzyme replacement therapy (ERT) with rhGAA for the previous ≥ 2

   - Subject 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.

   - Subject has upright FVC ≥ 30% of predicted normal value.

   - Subject or legally authorized representative(s) (LAR) (if applicable) provides written
   informed consent.

   - Subject and LAR(s) are willing and able to comply with study visits and study

   - Subject 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

Exclusion Criteria:

   - Subject is currently participating in an interventional study or has received gene or
   cell therapy.

   - Subject tests positive for AAV8 antibodies with titers >1:20 neutralizing.

   - Subject 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 subject to peripheral neuropathy will
   be evaluated.

   - Subject 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.

   - Subject has clinically significant underlying liver disease at Screening, or has any
   of the following:

   - Gamma glutamyl transferase (GGT) > 5.0 x upper limit of normal (ULN)

   - Active hepatitis B or C, and hepatitis B surface antigen (HBsAg), HB core antibody
   (HBcAb), HBV-DNA positivity or HCV-RNA viral load positivity, respectively.

   - Negative viral load assays in 2 samples, collected at least 6 months apart, will be
   required to be considered negative. Both natural clearers and those who have cleared
   HCV on antiviral therapy are eligible.

   - Currently on antiviral therapy for hepatitis B or C

   - Subject has serological or viral load evidence of HIV-1 or HIV-2.

   - Subject 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

   - Subject 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).

   - Subject has a history of hypersensitivity to β2 agonist drugs such as albuterol,
   levalbuterol, bitolterol, pirbuterol, terbutaline, salmeterol, which contraindicates
   pulmonary function testing.

   - Subject has an active viral infection based on clinical observation.

   - Subject has a history of or concurrent medical condition other than Pompe disease that
   could jeopardize safety of the subject or impact study results.

   - Subject 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.

   - Subject has a contraindication to study drug or to corticosteroids, or has
   demonstrated hypersensitivity to any of the components of the study drug.

   - Subject tests positive for GAA antibodies with titers > 1:50,000 total

   - Subject has a history of hypersensitivity to MRI contrast agents including gadolinium.

   - Subject has a known hypersensitivity to local anesthetics such as lidocaine.

   - Subject has a bleeding diathesis, e.g., due to anti-coagulation or anti-platelet

   - Subject has a concurrent medical condition (including uncontrolled diabetes, alcohol
   use disorder, certain autoimmune conditions, Lyme disease, active malignancy requiring
   chemotherapy and/or radiation, uremic nephropathy, known exposure to heavy metals)
   commonly associated with peripheral neuropathy. Other concurrent medical conditions
   that may predispose to peripheral neuropathy will be evaluated and action taken on a
   case-by-case basis, following discussion between the Investigator and Medical Monitor.

   - Subject has a history of diagnosed peripheral neuropathy or an abnormal NCS and/or
   mISS that is consistent with peripheral neuropathy.


genetic: zocaglusagene nuzaparvovec


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305