Gene Transfer Study in Patients With Late Onset Pompe Disease (FORTIS)

• ClinicalTrials.gov Identifier: NCT04174105
• Recruitment Status: Recruiting
• First Posted: November 22, 2019
• Last Update Posted: February 9, 2021
• Sponsor: Audentes Therapeutics
• Information provided by (Responsible Party): Audentes Therapeutics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Pompe Disease (Late-onset)	Genetic: AT845	Phase 1; Phase 2

Detailed Description:

This study (FORTIS) will evaluate the safety and efficacy of an investigational gene replacement therapy, AT845, in adult subjects with LOPD. Subjects will receive a single dose of AT845 delivered via intravenous (IV) infusion.

Up to 2 nominal dose levels of AT845 are planned to be evaluated in FORTIS. A single AT845 administration via IV infusion is planned for each subject. The initial dosing cohort will receive a single dose at 3x10^13 vg/kg of AT845. The second dose cohort will receive a single dose at 6x10^13 vg/kg of AT845.

The core observation period will be completed by Week 48 for each subject. Subjects will be followed for a total of 5 years after administration of AT845.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Up to 2 nominal dose levels of AT845 are planned to be evaluated in FORTIS. A single AT845 administration via intravenous (IV) infusion is planned for each subject.The initial dosing cohort will receive a single dose at 3x10^13 vg/kg of AT845. The second dose cohort will receive a single dose at 6x10^13 vg/kg of AT845.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 28, 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: January 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Initial Dose Cohort; 3x10^13 vg/kg of AT845 administered via intravenous infusion	Genetic: AT845; AT845 is an AAV8 vector delivering a functional copy of the human GAA gene, under the control of a muscle-specific promoter
Experimental: Second Dose Cohort; 6x10^13 vg/kg of AT845 administered via intravenous infusion	Genetic: AT845; AT845 is an AAV8 vector delivering a functional copy of the human GAA gene, under the control of a muscle-specific promoter

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability over time [ Time Frame: Change from baseline through Week 48 ]
   Frequency of adverse events, serious adverse events, and changes from baseline in relevant clinical laboratory tests
2. GAA protein expression [ Time Frame: Baseline and Week 12 ]
   Change from baseline in GAA protein expression in muscle biopsies at week 12
3. GAA enzymatic activity [ Time Frame: Baseline and Week 12 ]
   Change from baseline in GAA enzymatic activity in muscle biopsies at week 12

Secondary Outcome Measures :

1. Vector Copy Number and mRNA Transcripts [ Time Frame: Baseline and Week 12 ]
   Change from baseline in muscle biopsies
2. Thigh Fat Fraction [ Time Frame: Baseline and Month 18 ]
   Change from baseline in thigh fat fraction by MRI
3. 6-Minute Walk Test (for ambulatory patients) [ Time Frame: Baseline, Week 24 and Week 48 ]
   Change from baseline in the distance walked in the six minute walk test (6MWT), which is a standardized assessment of how far an individual can walk on a hard, flat surface in a period of 6 minutes
4. Forced Vital Capacity (FVC) [ Time Frame: Baseline, Week 24 and Week 48 ]
   Change from baseline in percentage of predicted FVC measured by pulmonary function testing
5. Maximum Inspiratory Pressure (MIP) [ Time Frame: Baseline, Week 24 and Week 48 ]
   Change from baseline in MIP measured by pulmonary function testing
6. Maximum Expiratory Pressure (MEP) [ Time Frame: Baseline, Week 24 and Week 48 ]
   Change from baseline in MEP measured by pulmonary function testing
7. EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Questionnaire [ Time Frame: Baseline and Week 48 ]
   Change from baseline in health profiles and overall health status as assessed by the EQ-5D-5L
8. Rasch-built Pompe-specific Activity (R-PAct) scale [ Time Frame: Baseline and Week 48 ]
   Change from baseline in the R-PAct scale, which was developed to measure Pompe patients' ability carry out daily life activities and social participation
9. Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: Baseline and Week 48 ]
   Change from baseline in scores of PROMIS short forms

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key 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 years.
• 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 must agree to use appropriate contraception following consent through 6 months post AT845 administration.

Key Exclusion Criteria:

• Subject is currently participating in an interventional study or has received gene or cell therapy.
• Subject tests positive for AAV8 neutralizing antibodies with titers above protocol specified threshold.
• Subject has received immune-modulating agents within 90 days before dosing (use of inhaled corticosteroids is allowed).
• Subject tests positive for GAA total antibodies with titers above protocol specified threshold.
• 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 in the opinion of the Investigator suggests a high risk for an allergic reaction to ERT).
• Subject has an active viral infection based on clinical observation.
• 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 in the opinion of the Investigator precludes enrollment.
• Subject has a clinically significant underlying liver disease.
• Subject has a contraindication to study drug or ingredients or to corticosteroids.

Contacts and Locations

Contacts

Contact: Audentes Patient Advocacy; +1-833-450-2759; trials@audentestx.com

Locations

United States, California

University of California Irvine, Department of Neurology; Recruiting

Orange, California, United States, 92868

Contact: Jennifer Scott 714-456-5956 stemcell@uci.edu

Principal Investigator: Tahseen Mozaffar, MD

Stanford University; Recruiting

Palo Alto, California, United States, 94304

Contact 650-725-4341 NeuromuscularResearch@stanford.edu

Principal Investigator: John Day, MD, PhD

United States, Georgia

To be announced; Not yet recruiting

Atlanta, Georgia, United States, 30322

United States, Michigan

To be announced; Not yet recruiting

Detroit, Michigan, United States, 48201

United States, Texas

To be announced; Not yet recruiting

Dallas, Texas, United States, 75207

United States, Utah

University of Utah, Division of Medical Genetics; Recruiting

Salt Lake City, Utah, United States, 84108

Contact: Kenzie Fait 801-585-7160 kenzie.fait@hsc.utah.edu

Principal Investigator: Nicola Longo, MD

Germany

Ludwig-Maximillians University of Munich; Not yet recruiting

Munich, Germany, 80336

Contact: Stephan Wenninger Stephan.Wenninger@med.uni-muenchen.de

Principal Investigator: Stephan Wenninger, MD

United Kingdom

Newcastle Upon Tyne Hospitals Foundation Trust Clinical Research Facility; Not yet recruiting

Newcastle upon Tyne, United Kingdom, NE1 4LP

Contact: Samantha Fitzsimmons 0191 241 8663 Sam.fitzsimmons@nhs.net

Principal Investigator: Jordi Diaz-Manera, MD, PhD

Sponsors and Collaborators

Audentes Therapeutics

Investigators

• Study Director: Nathan Bachtell, MD; Audentes Therapeutics

More Information

• Responsible Party: Audentes Therapeutics
• ClinicalTrials.gov Identifier: NCT04174105
• Other Study ID Numbers: AT845-01
• First Posted: November 22, 2019
• Last Update Posted: February 9, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Audentes Therapeutics:

LOPD

Additional relevant MeSH terms:

Glycogen Storage Disease Type II; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases