Clinical trial NCT03533673: AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease
Official title: A Phase 1 Study of the Safety of AAV2/8-LSPhGAA (ACTUS-101) in Late-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pompe Disease
Keywords: Gene Therapy
Lead sponsor: AskBio Inc
Sponsor class: INDUSTRY
First posted: 2018-05-23
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Open-label, ascending dose trial of ACTUS-101 administered intravenously.

Detailed description: This study will be a prospective, open-label trial designed to objectively assess the safety and bioactivity of ACTUS-101 in subjects diagnosed with Pompe disease, which is caused by a defect in acid α-glucosidase (GAA) gene. ACTUS-101 is intended to enable expression of a functional copy of the GAA gene in subject's hepatocytes.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Pompe disease by blood or skin fibroblast GAA assay and two pathogenic variants in the GAA gene,
* Age: Greater than or equal to 18 years at enrollment.
* Subjects are capable of giving written informed consent.
* Able to walk at least 100 meters on the 6MWT (with assistive devices permitted).
* FVC within the range of 30% to less 90% (inclusive) of predicted in the upright position.
* Subjects with a confirmed diagnosis of LOPD who have been treated with ERT for at least 104 weeks (inclusive) immediately preceding screening and receiving a stable dose of ERT for the 52-week period immediately preceding dosing.

Exclusion Criteria:

* Invasive ventilation required or noninvasive ventilation required while awake and upright.
* FVC \<20% of predicted (supine).
* Received any live vaccination 2 months prior to study Day 1.
* Pregnant or nursing mothers.
* Serology consistent with exposure to HIV, or serology consistent with active hepatitis A, B or C infection. Any active liver disease.
* Active infection based upon clinical symptoms.
* Having started respiratory muscle strength training in the last 6 months prior to study day 1 or having discontinued respiratory muscle strength training in the 6-month period preceding study day 1, or having started respiratory strength training greater than 6 months prior to study day 1 and unwilling to continue for the first year of study participation.
* Received an investigational drug or participated in another interventional study within 90 days prior to Study Day 1. Additionally, subjects cannot participate in any other interventional clinical trial throughout the first 78 weeks after receiving ACTUS-101.

Primary outcomes:
measure: Incidence of patient reported Treatment Emergent Adverse Events (TEAEs) (safety and tolerability)
timeFrame: 78 weeks
measure: Incidence of patient reported Serious Adverse Events (SAEs) (safety and tolerability)
timeFrame: 78 weeks
measure: Number of Participants With Abnormal Laboratory Values
timeFrame: 78 weeks
Secondary outcomes:
measure: Muscle GAA Bioactivity
timeFrame: 78 weeks
measure: Serum GAA Bioactivity
timeFrame: 78 weeks
measure: Glycogen content in muscle
timeFrame: 78 weeks
measure: Anti-rhGAA antibody formation
timeFrame: 78 weeks
measure: Muscle Status Testing - 6 minute walk test
timeFrame: 78 weeks
measure: Muscle Status Testing - Gross Motor Function Measure
timeFrame: 78 weeks
measure: Muscle Status Testing - Quick Motor Function Test (QMFT) Measure
timeFrame: 78 weeks
measure: Muscle Status Testing - Gait, Stairs, Gower, Chair
timeFrame: 78 weeks
measure: Pulmonary Function Testing
timeFrame: 78 weeks
measure: Muscle Status Testing - Timed up and Go (TUG)
timeFrame: 78 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
References: