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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04174105
Recruitment Status : Recruiting
First Posted : November 22, 2019
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Audentes Therapeutics

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 Dose 1 of AT845. The second dose cohort will receive a single dose at Dose 2 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.

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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 Dose 1 of AT845. The second dose cohort will receive a single dose at Dose 2 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
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : January 2027


Arm Intervention/treatment
Experimental: Initial Dose Cohort
Dose 1 of AT845 administered via intravenous infusion
Genetic: AT845
AT845 is a AAV8 vector delivering a functional copy of the human GAA gene

Experimental: Second Dose Cohort
Dose 2 of AT845 administered via intravenous infusion
Genetic: AT845
AT845 is a AAV8 vector delivering a functional copy of the human GAA gene




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 8 ]
    Change from baseline in GAA protein expression in muscle biopsies at week 8

  3. GAA enzymatic activity [ Time Frame: Baseline and Week 8 ]
    Change from baseline in GAA enzymatic activity in muscle biopsies at week 8


Secondary Outcome Measures :
  1. Vector Copy Number and mRNA Transcripts [ Time Frame: Baseline and Week 8 ]
    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



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04174105


Contacts
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Contact: Audentes Patient Advocacy +1-415-715-9189 trials@audentestx.com

Locations
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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, Utah
University of Utah, Division of Medical Genetics Not yet recruiting
Salt Lake City, Utah, United States, 84108
Contact: Jenny Billy    801-585-9008    jenny.billy@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
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Responsible Party: Audentes Therapeutics
ClinicalTrials.gov Identifier: NCT04174105    
Other Study ID Numbers: AT845-01
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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