Clinical trial NCT02240407: Re-administration of Intramuscular AAV9 in Patients With Late-Onset Pompe Disease
Official title: Evaluation of Re-administration of Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase (rAAV9-DES-hGAA) in Patients With Late-Onset Pompe Disease (LOPD)
Conditions: 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.
Interventions:
description: 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).
name: Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase
other_name: rAAV9-DES-hGAA
type: Genetic
description: 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.
name: Rapamycin
other_name: Sirolimus
type: Drug
description: Same volume as rAAV9-DES-hGAA injection will be used.
name: saline
other_name: Excipient
type: Other
description: 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.
name: Rituxan
other_name: Rituximab
type: Drug
description: 25-50mg will be provided before each Rituximab dose.
name: Diphenhydramine
other_name: Benadryl
type: Drug
description: We will provide 650 mg of tylenol before each dose of Rituximab.
name: Acetaminophen
other_name: Tylenol
type: Drug
description: Lidocaine will be used based on standard of care: Percutaneous infiltration, concentration 0.5-1%, 1-10 mL, 5-300mg total dose.
name: Lidocaine
other_name: Xylocaine
type: Drug
description: Topical anesthesia cream will be used prior to gene therapy/saline injection.
name: LMX 4 Topical Cream
other_name: Lidocaine 4%
type: Drug
Study arms:
design_group_description: Each subject will receive Rituxan and Rapamycin 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. Diphenhydramine and acetaminophen will be provided before each Rituxan dose. Immune Globulin will be administered to each subject every other month after first exposure to Rituxan and as clinical necessary. Lidocaine will be administered through percutaneous infiltration before injection of the study agent. Side of administration will be randomized at first Recombinant Adeno-Associated Virus Acid Alpha-Glucosidase injection.
design_group_title: rAAV9-DES-hGAA vector
design_group_type: Experimental
design_group_description: Each subject will receive Rituxan and Rapamycin 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. Diphenhydramine and acetaminophen will be provided before each Rituxan dose. Immune Globulin will be administered to each subject every other month after first exposure to Rituxan and as clinical necessary. Lidocaine will be administered through percutaneous infiltration before injection of the study agent. Side of administration will be randomized at first saline injection.
design_group_title: Excipient
design_group_type: Sham Comparator
Sponsor: University of Florida
Collaborators: Lacerta Therapeutics, Inc.
Drug name mappings:
name: 对乙酰氨基酚
lang: CN
name: Acetaminophen
lang: EN
name: アセトアミノフェン
lang: JP
name: Recombinant adeno-associated virus acid alpha-glucosidase(University of Florida)
lang: EN
name: 西罗莫司
lang: CN
name: Sirolimus
lang: EN
name: シロリムス
lang: JP
name: 利多卡因
lang: CN
name: Lidocaine
lang: EN
name: リドカイン
lang: JP
name: 盐酸苯海拉明
lang: CN
name: Diphenhydramine Hydrochloride
lang: EN
name: ジフェンヒドラミン塩酸塩
lang: JP
name: 利妥昔单抗
lang: CN
name: Rituximab
lang: EN
name: リツキシマブ（遺伝子組換え）
lang: JP