Re-administration of Intramuscular AAV9 in Patients With Late-Onset Pompe Disease

Summary

A recombinant AAV vector has been generated to carry the codon-optimized acid alpha-glucosidase (coGAA) gene expressed from a human desmin enhancer/promoter (DES). The proposed clinical trial is a within-participant, double-blind, randomized, phase I controlled study evaluating the toxicology, biodistribution and potential activity of re-administration of rAAV9-DES-hGAA injected intramuscularly into the TA. Nine participants (18 to 50-years old) who reside within the United States with Late-Onset Pompe Disease (LOPD) will be included. The goal of the immune modulation strategy is to ablate B-cells (Rituximab and Sirolimus) prior to the initial exposure to the study agent in one leg and the subsequent exposure of the same vector to the contralateral leg after four months. At each study agent dosing, the contralateral leg will receive excipient. Patients will act as their own controls. Repeated measures, at baseline and during the following 3 months after each injection, will assess the safety, biochemical and functional impact of the vector.

Conditions

• Pompe Disease

Interventions

GENETIC

Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase

The dose selected for this study is a fixed dose of 4.6 x 10\^13 vg per TA muscle (range of 7.64 x 10\^11 vg/gm to 4.6 x 10\^11 vg/gm based on TA weight).

DRUG

Rapamycin

Patients will receive Rapamycin (dose 0.6-2 mg/m\^2/day, adjusted to maintain a trough serum sirolimus level of 2-4 ng/mL.) every day starting from 7 days before first injection of AAV9 until four months after second injection.

OTHER

saline

Same volume as rAAV9-DES-hGAA injection will be used.

DRUG

Rituxan

Patients will receive Rituxan (dose: 750 mg/m\^2 twice) 21 and 7 day prior first AAV9 injection, with a Rituxan dose 375 mg/m\^2 on the day of the injection. Rituxan will be repeated 7 days prior to the 2nd injection of the vector. The maintenance dose of Rituxan will be 375 mg/m\^2.

DRUG

Diphenhydramine

25-50mg will be provided before each Rituximab dose.

DRUG

Acetaminophen

We will provide 650 mg of tylenol before each dose of Rituximab.

DRUG

Lidocaine

Lidocaine will be used based on standard of care: Percutaneous infiltration, concentration 0.5-1%, 1-10 mL, 5-300mg total dose.

DRUG

LMX 4 Topical Cream

Topical anesthesia cream will be used prior to gene therapy/saline injection.

Sponsors & Collaborators

• Lacerta Therapeutics

  collaborator UNKNOWN

• University of Florida

  lead OTHER

Principal Investigators

• Manuela Corti, P.T., PhD. · University of Florida

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-10-17

Primary Completion

2021-08-26

Completion

2021-08-26

FDA Drug

Yes

Countries

• United States

Study Locations